bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of GPCP Monthly and Daily Precipitation Estimates with High-Latitude Gauge Observations
Authors: Bolvin David T. , Adler Robert F. , Huffman George J. , Nelkin Eric J. , Poutiainen Jani P.
Published: March 2009

Monthly and daily products of the Global Precipitation Climatology Project (GPCP) are evaluated through a comparison with Finnish Meteorological Institute (FMI) gauge observations for the period January 1995–December 2007 to assess the quality of the GPCP estimates at high latitudes. At the monthly scale both the final GPCP combination satellite–gauge (SG) product is evaluated, along with the satellite-only multisatellite (MS) product. The GPCP daily product is scaled to sum to the monthly product, so it implicitly contains monthly-scale gauge influence, although it contains no daily gauge information. As expected, the monthly SG product agrees well with the FMI observations because of the inclusion of limited gauge information. Over the entire analysis period the SG estimates are biased low by 6% when the same wind-loss adjustment is applied to the FMI gauges as is used in the SG analysis. The interannual anomaly correlation is about 0.9. The satellite-only MS product has a lesser, but still reasonably good, interannual correlation (∼0.6) while retaining a similar bias due to the use of a climatological bias adjustment. These results indicate the value of using even a few gauges in the analysis and provide an estimate of the correlation error to be expected in the SG analysis over ocean and remote land areas where gauges are absent. The daily GPCP precipitation estimates compare reasonably well at the 1° latitude × 2° longitude scale with the FMI gauge observations in the summer with a correlation of 0.55, but less so in the winter with a correlation of 0.45. Correlations increase somewhat when larger areas and multiday periods are analyzed. The day-to-day occurrence of precipitation is captured fairly well by the GPCP estimates, but the corresponding precipitation event amounts tend to show wide variability. The results of this study indicate that the GPCP monthly and daily fields are useful for meteorological and hydrological studies but that there is significant room for improvement of satellite retrievals and analysis techniques in this region. It is hoped that the research here provides a framework for future high-latitude assessment efforts such as those that will be necessary for the upcoming satellite-based Global Precipitation Measurement (GPM) mission.
Equatorially Bounded Zonally Propagating Linear Waves on a Generalized β Plane
Authors: Fruman Mark D.
Published: March 2009

Meridionally confined zonally propagating wave solutions to the linear hydrostatic Boussinesq equations on a generalized equatorial β plane that includes the “nontraditional” Coriolis force terms associated with the poleward component of planetary rotation are calculated. Kelvin, Rossby, inertia–gravity, and mixed Rossby–gravity modes generalize from the traditional model with the dispersion relation unchanged. The effects of the nontraditional terms on all waves are the curving upward with latitude of the surfaces of constant phase and the equatorial trapping width of the solutions (the equatorial radius of deformation) increasing by order (Ω/N)2 compared to the traditional case, where Ω is the planetary rotation rate and N the buoyancy frequency. In addition, for the Rossby, inertia–gravity, and mixed Rossby–gravity modes, there is a phase shift of O(Ω/N) in the zonal and vertical velocity components relative to the meridional component, and their spatial structures are further modified by differences of O(Ω/N)2. For the Rossby and inertia–gravity waves, the modifications depend also on the phase speed of the wave. In the limit N ≫ Ω, the traditional approximation is justified and lines of constant phase in the y–z plane become horizontal, whereas for N ≪ Ω phase lines become everywhere almost parallel to the planetary rotation vector. In both limits, the phase lines are perpendicular to the dominant restoring force—respectively, gravity and the centrifugal force associated with the solid-body rotation of the atmosphere at rest in the rotating frame.
Polar Climate Instability and Climate Teleconnections from the Arctic to the Midlatitudes and Tropics
Authors: Vettoretti Guido , d’Orgeville Marc , Peltier William R. , Stastna Marek
Published: March 2009

It is generally accepted that the ocean thermohaline circulation plays a key role in polar climate stability and rapid climate change. Recently reported analyses of the impact of anomalous freshwater outflows from the North American continent onto either the North Atlantic or Arctic Oceans demonstrate that, in either case, a clear reduction in the Atlantic meridional overturning circulation, accompanied by an increase in sea ice extent, is predicted. The results also reconcile proxy-inferred Younger Dryas Greenland temperature variations. The aim of the present work is to provide a detailed investigation of the pathways along which the signal associated with overturning circulation anomalies propagates into both the midlatitudes and the tropics and the effect such teleconnections have on the tropical ocean–atmosphere system. The authors consider both the impact of substantial slowing of the overturning circulation due to freshwater forcing of the North Atlantic as well as its recovery after the anomalous forcing has ceased. The changes in tropical climate variability are shown to manifest themselves in shifts of both the typical time scale and intensity of ENSO events in the model. Evidence is presented for mechanisms that involve both atmospheric and oceanic pathways through which such Northern Hemisphere high-latitude events are communicated into both the midlatitudes and the tropics and thereafter transformed into changes in the nature of tropical variability.
Impact of Greenhouse Gas Concentration Changes on Surface Energetics in IPSL-CM4: Regional Warming Patterns, Land–Sea Warming Ratios, and Glacial–Interglacial Differences
Authors: Laîné Alexandre , Kageyama Masa , Braconnot Pascale , Alkama Ramdane
Published: March 2009

The temperature response to a greenhouse gas (GHG) concentration change is studied in an ocean–atmosphere coupled model—L’Institut Pierre-Simon Laplace Coupled Model, version 4 (IPSL-CM4)—for both a glacial and an interglacial context. The response to a GHG concentration changing from Last Glacial Maximum (LGM) to preindustrial values is similar for both climatic contexts in terms of temperature pattern, but the magnitude is greater under modern ones. The model simulates the classical amplification of the temperature response in the northern high latitudes compared to lower latitudes and over the land surfaces compared to the ocean.

The physical reasons for the differential warming according to the latitude and to the surface type are studied through an analysis of the energy flux changes, which are decomposed to consider and quantify many different physical processes. The results highlight the role of many different factors in the thermal response to a GHG forcing for different regions, and stress, for instance, the large effect of increased water vapor concentration in the atmosphere. Concerning the land–sea warming ratio, several fluxes contribute to the final value of the ratio, with latent flux having the greatest influence. The different contributions are quantified. The comparison of the flux changes between the interglacial and glacial contexts shows that the differences are more than a simple effect of different surface emissions of the base state. It suggests that the climatic context is particularly important for the cloud and oceanic advection responses to the forcing, along with albedo effects.
The Extreme Cold Anomaly over Southeast Asia in February 2008: Roles of ISO and ENSO*
Authors: Hong Chi-Cherng , Li Tim
Published: March 2009

A record-breaking, long-persisting extreme cold anomaly (ECA) over Southeast Asia, accompanied by an intraseasonal convection over the Maritime Continent, is identified during the La Niña mature phase in February 2008. The cause of the ECA, in particular the role of the intraseasonal oscillation (ISO) and El Niño–Southern Oscillation (ENSO) on the ECA, is investigated by diagnosing observations and conducting numerical experiments.

The ECA is associated with an enhanced prolonged Siberian high (SH) and a persistent northerly anomaly over Southeast Asia. In contrast to conventional cold surges, which are characterized by a synoptic time scale (less than 10 days), the northerly anomaly associated with the ECA persisted for a month or so. The onset of the northerly anomaly is concurrent with a phase change of an ISO over Sumatra. Unlike the normal ISO that continues its eastward journey, the convection associated with this ISO stationed there during all of February 2008. Numerical experiments with an anomaly atmospheric GCM suggest that the ISO heating over the Maritime Continent is responsible for initiating and maintaining the northerly anomaly.

The westward progression of the La Niña is crucial for blocking the ISO. The circulation and SST anomalies associated with the La Niña moved westward at a speed of about 15° longitude per month. By early February, the suppressed convective anomaly had moved to the far western Pacific. The westward shift of the cold episode prevented the ISO from moving farther eastward. In addition to its blocking effect, the La Niña also enhanced the heating over the Maritime Continent through the anomalous Walker circulation. Therefore, it is the combined effect of the ISO and ENSO that maintained a prolonged positive heating anomaly, which resulted in a persistent northerly anomaly and thus the ECA.
Review and Case Study of Sounds Associated with the Lightning Electromagnetic Pulse
Authors: Coleman Timothy A. , Knupp Kevin R. , Tarvin John T.
Published: March 2009

The electromagnetic pulses (EMPs) associated with two lightning flashes on 22 July 2008 in central Alabama produced audible clicking sounds. These clicks were observed almost simultaneously with the lightning flashes, but a significant period of time before the thunder. The lightning flashes and associated sounds were recorded in digital video and audio by a video camera. Based on theories primarily developed to explain reports of sounds associated with aurora and meteors entering the earth’s atmosphere, it appears that the sounds were associated with transduction of the electromagnetic energy at audible frequencies into vibrations in objects near the camera. Coronal discharges are also possible. Examination of spectrograms of the clicks and the subsequent thunder, and comparison to measurements of the normalized light intensity in each frame of video, show that the clicks must have been associated with sounds in nearby objects. Therefore, the sounds were associated with the lightning EMP.
Perpetua
Authors: Parvis Sara
Published: March 2009

Perpetua was martyred with her fellow catechumens in Carthage in 203. Her story is told in the Passion of Perpetua and Felicity , a composite document made up of Perpetua's prison diary, her catechist Saturus' account of his own dream, and a wraparound narrative describing the exemplary deaths of the whole group. The writing illustrates the pouring out of the Spirit on young men and women, slaves male and female, and youngsters and elders (cf. Joel 2:28, Acts 2:17—18). It may have Montanist connections, though these should not be overstated.
Type 1 Diabetes Among Adolescents
Authors: Di Battista Ashley M. , Hart Trevor A. , Greco Laurie , Gloizer Jan
Published: March 2009

Purpose

The aim of this study was to examine the association between social anxiety and adherence to diabetes self-care and quality of life and to determine the effects of fear of hypoglycemia on these associations in adolescents with type 1 diabetes. It is hypothesized that (1) social anxiety will be negatively associated with adherence and quality of life and (2) that fear of hypoglycemia will mediate this relationship. It is also hypothesized that (3) girls will have higher social anxiety than boys.

Methods

Adolescents with type 1 diabetes were recruited during clinic visits at 2 international centers. Participants answered a survey containing questionnaires on social anxiety, behavioral adherence to the diabetes self-care regimen, quality of life, fear of hypoglycemia, and last hemoglobin A1C results.

Results

Seventy-six adolescents (33 boys, 43 girls), mean age 15.9 (1.44) years, participated. Social anxiety levels are not statistically different between genders. In boys, social anxiety is associated with worse diet and insulin injection adherence; no associations are found in girls. Social anxiety is positively correlated with poor quality of life in both genders. Fear of hypoglycemia mediates the relationship between social anxiety and insulin adherence in boys.

Conclusions

Findings suggest that social anxiety, which is common in general populations of adolescents, may interfere with behavioral adherence and quality of life among adolescents with type 1 diabetes. Screening and treatment of social anxiety may result in better adherence and increased quality of life.
Bulla gouldiana period exhibits unique regulation at the mrnA and Protein Levels
Authors: Constance Cara M. , Green Carla B. , Tei Hajime , Block Gene D.
Published: March 2009

The authors cloned the period ( per) gene from the marine mollusk Bulla gouldiana, a well-characterized circadian model system. This allowed them to examine the characteristics of the per gene in a new phylum, and to make comparisons with the conserved PER domains previously characterized in insects and vertebrates. Only one copy of the per gene is present in the Bulla genome, and it is most similar to PER in two insects: the cockroach, Periplaneta americana, and silkmoth, Antheraea pernyi. Comparison with Drosophila PER (dPER) and murine PER 1 (mPER1) sequence reveals that there is greater sequence homology between Bulla PER (bPER) and dPER in the regions of dPER shown to be important to heterodimerization between dPER and Drosophila timeless. Although the structure suggests conservation between dPER and bPER, expression patterns differ. In all cells and tissues examined that are peripheral to the clock neurons in Bulla, bPer mRNA and protein are expressed constitutively in light:dark (LD) cycles. In the identified clock neurons, the basal retinal neurons (BRNs), a rhythm in bPer expression could be detected in LD cycles with a peak at zeitgeber time (ZT) 5 and trough expression at ZT 13. This temporal profile of expression more closely resembles that of mPER1 than that of dPER. bPer rhythms in the BRNs were not detected in continuous darkness. These analyses suggest that clock genes may be uniquely regulated in different circadian systems, but lead to similar control of rhythms at the cellular, tissue, and organismal levels.
5-HT1B Receptor Knockout Mice Exhibit an Enhanced Response to Constant Light
Authors: Sollars Patricia J. , Ogilvie Malcolm D. , Rea Michael A. , Pickard Gary E.
Published: March 2009

Serotonin (5-HT) can act presynaptically at 5-HT1Breceptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT1Breceptor agonists (1) inhibit light-inducedphase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve–evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT1Bpresynaptic receptors would result in an amplified response of the SCN to light, the period ([.tau]) of the circadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT1Breceptor knockout (KO) mice and genetically matched wild- typeanimals. Under constant light (LL) conditions, the [.tau] of 5-HT1Breceptor KO mice was significantly greater than the [.tau] of wild-type mice. Aquantitative analysis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in [.tau] was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT1Breceptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT1Breceptor KO mice in the rate of reentrainment toa6h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5- HT1Breceptor KO mice to LLconditions is consistent with the hypothesis that the endogenous activation of 5-HT1Bpresynaptic receptors modulates circadian behavior by attenuating photic input to the SCN.
Tube Feeding in Patients With Dementia: Where Are We?
Authors: DeLegge Mark H.
Published: March 2009

Dementia is a common diagnosis and accounts for significant morbidity and mortality. In the United States, the practice of medicine commonly dictated that dementia patients with dysphagia should receive a feeding tube. A review of the evidence in 1999 was completed to understand the validity of the premise of an improvement in a dementia patient's survival, quality of life, malnutrition, and comorbid diseases with tube feeding. The available literature reviewed was sparse. The retrospective and prospective observational studies noted no improvement in the above‐mentioned outcomes in dementia patients with the use of tube feeding. Interestingly, a recent retrospective review denoted that dementia patients had no worse survival than patients with other diseases receiving a feeding tube and tube feedings. A prospective study comparing tube feeding to hand feeding in the dementia population is sorely needed.
Degradation Property of Commercially Available Si-containing Polyimide in Simulated Atomic Oxygen Environments for Low Earth Orbit
Authors: Yokota Kumiko , Abe Shingo , Tagawa Masahito , Iwata Minoru , Miyazaki Eiji , Ishizawa Jun-Ichiro , Kimoto Yugo , Yokota Rikio
Published: March 2009

Real-time measurement of the erosion rate of a commercially available Si-containing polyimide (BSF30) under hyperthermal atomic oxygen (AO) beam exposure condition, which simulates the AO environment in low Earth orbit (LEO), was performed. It was found that the erosion rate of BSF30 decreased with increasing AO fluence and it reached as low as 4% of the standard PMDA-ODA polyimide. X-ray photoelectron spectroscopy confirmed that the surface of AO-exposed BSF30 was covered by a SiO2 layer which functioned as a protective coating. In contrast, an SiO2 surface layer thick enough to protect bulk BSF30 was not formed by thermal AO, which was generated by vacuum ultraviolet exposure in an O2 atmosphere. Exposure to hyperthermal AO collision in LEO can also form an SiO2 layer which enables the surface to be self-healing and is desirable for a polyimide that would be used in LEO.
Investigation of Structure/property Relationships of Polytriazoles
Authors: Tian Jianjun , Wang Xiaofei , Wan Liqiang , Hu Yanhong , Huang Farong , Du Lei
Published: March 2009

Five polytriazole resins, TAMTMB-BPF, TAMTMB-BPA, TAMTMB-BPK, TAMTMB-BPE, and TAMTMB-BPR, were prepared from 1,3,5-tris(azidomethyl)-2,4,6-trimethylbenzene (TAMTMB) and dipropargyl ethers of hexafluorobisphenol A (BPF), bisphenol A (BPA), 4,4'-dihydroxybenzophenone (BPK), 4,4'-dihydroxydiphenyl ether (BPE), and resorcinol (BPR), respectively. The resins were characterized by Fourier transform infrared spectrometry, differential scanning calorimetry, dynamic mechanical analysis, and thermogravimetric analysis. The results illustrate that the structures of dipropargyl ethers had no obvious effect on the curing behavior of the polytriazole resins and the thermal stability of the cured resins. The polytriazole resins could be cured at 80 °C and further post-cured at higher temperature. The cured resins had a thermal decomposition temperature Td5 near 360 °C. However, the structural units of the polytriazole resins influenced the glass transition temperature T g, dielectric properties, and mechanical properties of the cured resins to some extent. The cured TAMTMB-BPF resin had the highest Tg (226 °C) and best dielectric properties among the resins, whereas the cured TAMTMB-BPR resin showed the highest flexural strength of 200.6 MPa.
Chicago: down but not out
Authors: Hagerty Bill
Published: March 2009

The U.S. newspaper industry is in deep crisis and the state of the two titles in America’s greatest newspaper city, Chicago, is a case in point. In the city that spawned The Front Page, the iconic play and movie about 20th century journalism, both the Tribune and the Sun-Times are coping with the twin problems of falling advertising revenue and falling sales. Bill Hagerty, BJR’s editor, visits the city and meets the papers’ two editors to discuss their problems. In spite of the gloom, he discovers that they remain optimistic about the future.
Putting “Organizations” into an Organization Theory Course: A Hybrid CAO Model For Teaching Organization Theory
Authors: Hannah David R. , Venkatachary Ranga
Published: March 2009

In this article, the authors present a retrospective analysis of an instructor’s multiyear redesign of a course on organization theory into what is called a hybrid Classroom-as-Organization model. It is suggested that this new course design served to apprentice students to function in quasi-real organizational structures. The authors further argue that the quality of students’ apprenticeship experiences was influenced by three factors: (a) the relevance of the course content, (b) the authenticity of classroom exercises and activities, and (c) the physical context of the course. The authors substantiate their arguments by incorporating quantitative and qualitative data from eight rounds of course evaluations in their analyses. It is believed that the ideas discussed herein will be particularly interesting to instructors of organization theory and to other instructors who use Classroom-as-Organization models.
Cultural Values Predict Subsequent Economic Growth
Authors: Minkov Michael , Blagoev Vesselin
Published: March 2009

The relationship between cultural values and economic growth has been the subject of much controversy. A few studies have shown statistical correlations between measurements of national cultural values and previous growth but this is a dubious approach to the question of whether culture is the cause or the result of such growth. This study uses World Values Survey items from 1998 to 1999 and demonstrates that some values form a nation-level cultural dimension which predicts subsequent, and explains previous, economic growth across more than 70 countries. The dimension contrasts the importance of thrift versus the importance of leisure and good human relationships. Its nature is in full accordance with views of development economists who describe modern economic development as, among other things, a function of saving, investment, and hard work.
Constraints in the Implementation of Performance Management Systems in Developing Countries
Authors: Ohemeng Frank Louis Kwaku
Published: March 2009

Performance management has become a key element in modern public sector governance. As a result, many developing countries have introduced it as a means to measure organizational and individual efficiency in order to ensure that public sector organizations meet the needs of the public. However, the implementation of performance management systems in many of these countries has been affected by a number of institutional and capacity constraints such as culture, institutional fragmentation, public apathy, and leadership support, thus making it difficult for many of them to realize the `benefits' of such a system. This article examines these constraints with a focus on Ghana. Utilizing information obtained from interviews of senior bureaucrats and chief executive officers of state-owned enterprises (SOEs), it is argued that without a critical analysis of these constraints, performance management no matter how attractive it may be will not achieve the desired results in developing countries.
Trapeziectomy for Trapeziometacarpal Joint Osteoarthritis: Is Ligament Reconstruction and Temporary Stabilisation of the Pseudarthrosis with a Kirschner Wire Important?
Authors: DAVIS T. R. C. , PACE A.
Published: March 2009

This randomised prospective study compared two operations for trapeziometacarpal joint osteoarthritis: trapeziectomy with Flexor carpi radialis ligament reconstruction, tendon interposition and Kirschner wire insertion followed by splintage for 6 weeks (T+LRTI) and excision of the trapezium with no Kirschner wire and immobilisation of the thumb in a soft bandage for only 3 weeks (T). Sixty-seven thumbs with trapeziectomy (T) and 61 with trapeziectomy and ligament reconstruction and tendon interposition (T+LRTI) were assessed preoperatively and at 3-months and 1-year after surgery. Forty-seven percent and 73% of patients reported no pain or only aching after use at 3-months and 1-year respectively and the DASH and Patient Evaluation Measure (PEM) outcome scores reduced postoperatively indicating improved function. However the pain, DASH and PEM scores, and also key and tip thumb pinch and all the other clinical outcome measures, did not differ significantly between the two groups at either 3-months or 1-year after surgery.
The Effect of Miniscalpel-Needle Versus Steroid Injection for Trigger Thumb Release
Authors: CHAO M. , WU S. , YAN T.
Published: March 2009

This study compared the result of percutaneous release using a miniscalpel-needle and steroid injection in 93 trigger thumbs in 83 patients. The patients were randomly assigned to either miniscalpel-needle percutaneous release (group A) or steroid injection (group B). Visual analogue pain scales and patients’ satisfaction were evaluated at baseline, 1 and 12 months. One patient in group A and two patients in group B were lost to follow-up. Forty-four of the 46 trigger thumbs in group A and 12 of 47 trigger thumbs in group B had satisfactory results at 12 months. No digital nerve injury occurred in either group. Percutaneous release with a miniscalpel-needle had a higher success rate than steroid injection.
Mini Open Carpal Tunnel Release Using Knifelight®: Evaluation of the Safety and Effectiveness of Using a Single Wrist Incision (Cadaveric Study)
Authors: TEH K. K. , NG E. S. , CHOON D. S. K.
Published: March 2009

This cadaveric study evaluates the margin of safety and technical efficacy of mini open carpal tunnel release performed using Knifelight® (Stryker Instruments) through a transverse 1 cm wrist incision. A single investigator released 32 wrists in 17 cadavers. The wrists were then explored to assess the completeness of release and damage to vital structures including the superficial palmar arch, palmar cutaneous branch and recurrent branch of the median nerve. All the releases were complete and no injury to the median nerve and other structures were observed. The mean distance of the recurrent motor branch to the ligamentous divisions was 5.7 ± 2.4 mm, superficial palmar arch was 8.7 ± 3.1 mm and palmar cutaneous branch to the ligamentous division was 7.2 ± 2.4 mm. The mean length of the transverse carpal ligament was 29.3 ± 3.7 mm. Guyon’s canal was preserved in all cases.
Day Case Total Joint Arthroplasty in the Hand: Results in a District General Hospital
Authors: NISAR A. , SHAH Z. , PENDSE A. , CHAKRABARTI I.
Published: March 2009

The aim of this study was to review the short-term results of joint replacement in the hand, comparing those done as day cases with those done as inpatients. Procedures included trapeziometacarpal, metacarpophalangeal and proximal interphalangeal joint arthroplasties. For day cases a portable laminar flow machine was used, whereas inpatient procedures were carried out in a laminar flow theatre. The postoperative regime was the same in the two groups. The mean follow-up was 12 months. There was no difference in complications, revisions, pain scores and Quick-DASH scores. No early loosening has been detected in any patients at a minimum of 12 months’ follow-up. All patients who had day surgery were satisfied with the care. The results of day case small joint arthroplasty of the hand are similar to those in inpatients.
Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity
Authors: Capoccia Benjamin J. , Robson Debra L. , Levac Krysta D. , Maxwell Dustin J. , Hohm Sarah A. , Neelamkavil Marian J. , Bell Gillian I. , Xenocostas Anargyros , Link Daniel C. , Piwnica-Worms David , Nolta Jan A. , Hess David A.
Published: March 2009

The development of cell therapies to treat peripheral vascular disease has proven difficult because of the contribution of multiple cell types that coordinate revascularization. We characterized the vascular regenerative potential of transplanted human bone marrow (BM) cells purified by high aldehyde dehydrogenase (ALDHhi) activity, a progenitor cell function conserved between several lineages. BM ALDHhi cells were enriched for myelo-erythroid progenitors that produced multipotent hematopoietic reconstitution after transplantation and contained nonhematopoietic precursors that established colonies in mesenchymal-stromal and endothelial culture conditions. The regenerative capacity of human ALDHhi cells was assessed by intravenous transplantation into immune-deficient mice with limb ischemia induced by femoral artery ligation/transection. Compared with recipients injected with unpurified nucleated cells containing the equivalent of 2- to 4-fold more ALDHhi cells, mice transplanted with purified ALDHhi cells showed augmented recovery of perfusion and increased blood vessel density in ischemic limbs. ALDHhi cells transiently recruited to ischemic regions but did not significantly integrate into ischemic tissue, suggesting that transient ALDHhi cell engraftment stimulated endogenous revascularization. Thus, human BM ALDHhi cells represent a progenitor-enriched population of several cell lineages that improves perfusion in ischemic limbs after transplantation. These clinically relevant cells may prove useful in the treatment of critical ischemia in humans.
Notes from the Director, National Heart, Lung, and Blood Institute: transitions
Authors: Nabel Elizabeth G.
Published: March 2009

During this time of transition in the federal government and the National Institutes of Health, I write to assure the Blood community of the National Heart, Lung, and Blood Institute's (NHLBI) commitment to new and established investigators as outlined in the NHLBI Strategic Plan. This perspective discusses the NHLBI budget for the fiscal year 2009 and new policies for funding early stage investigators and revised grant applications.
Cellular localization of Y-box binding protein 1 in brain tissue of rats, macaques, and humans
Authors: Unkrüer Bernadette , Pekcec Anton , Fuest Christina , Wehmeyer Andrea , Balda Maria S , Horn Anja , Baumgärtner Wolfgang , Potschka Heidrun
Published: March 2009

Background

The Y-box binding protein 1 (YB-1) is considered to be one of the key regulators of transcription and translation. However, so far only limited knowledge exists regarding its cellular distribution in the adult brain.

Results

Analysis of YB-1 immunolabelling as well as double-labelling with the neuronal marker NeuN in rat brain tissue revealed a predominant neuronal expression in the dentate gyrus, the cornu ammonis pyramidal cell layer, layer III of the piriform cortex as well as throughout all layers of the parahippocampal cortex. In the hilus of the hippocampus single neurons expressed YB-1. The neuronal expression pattern was comparable in the hippocampus and parahippocampal cortex of adult macaques and humans. Double-labelling of YB-1 with the endothelial cell marker Glut-1, the multidrug transporter P-glycoprotein, and the astrocytic marker GFAP did not indicate a co-localization. Following status epilepticus in rats, no induction of YB-1 occurred in brain capillary endothelial cells and neurons.

Conclusion

In conclusion, our study demonstrates that YB-1 is predominantly expressed in neurons in the adult brain of rats, macaques and humans. Lack of a co-localization with Glut-1 and P-glycoprotein argues against a direct role of YB-1 in the regulation of blood-brain barrier P-glycoprotein.
Accumulation and processing of a recombinant protein designed as a cleavable fusion to the endogenous Rubisco LSU protein in Chlamydomonas chloroplast
Authors: Muto Machiko , Henry Ryan E , Mayfield Stephen P
Published: March 2009

Background

Expression of recombinant proteins in green algal chloroplast holds substantial promise as a platform for the production of human therapeutic proteins. A number of proteins have been expressed in the chloroplast of Chlamydomonas reinhardtii, including complex mammalian proteins, but many of these proteins accumulate to significantly lower levels than do endogenous chloroplast proteins. We examined if recombinant protein accumulation could be enhanced by genetically fusing the recombinant reporter protein, luciferase, to the carboxy-terminal end of an abundant endogenous protein, the large subunit of ribulose bisphosphate carboxylase (Rubisco LSU). Additionally, as recombinant proteins fused to endogenous proteins are of little clinical or commercial value, we explored the possibility of engineering our recombinant protein to be cleavable from the endogenous protein in vivo. This strategy would obviate the need for further in vitro processing steps in order to produce the desired recombinant protein. To achieve this, a native protein-processing site from preferredoxin (preFd) was placed between the Rubisco LSU and luciferase coding regions in the fusion protein construct.

Results

The luciferase from the fusion protein accumulated to significantly higher levels than luciferase expressed alone. By eliminating the endogenous Rubisco large subunit gene (rbcL), we achieved a further increase in luciferase accumulation with respect to luciferase expression in the WT background. Importantly, near-wild type levels of functional Rubisco holoenzyme were generated following the proteolytic removal of the fused luciferase, while luciferase activity for the fusion protein was almost ~33 times greater than luciferase expressed alone. These data demonstrate the utility of using fusion proteins to enhance recombinant protein accumulation in algal chloroplasts, and also show that engineered proteolytic processing sites can be used to liberate the exogenous protein from the endogenous fusion partner, allowing for the purification of the intended mature protein.

Conclusion

These results demonstrate the utility of fusion proteins in algal chloroplast as a method to increase accumulation of recombinant proteins that are difficult to express. Since Rubisco is ubiquitous to land plants and green algae, this strategy may also be applied to higher plant transgenic expression systems.
Molecular models of human P-glycoprotein in two different catalytic states
Authors: Becker Jean-Paul , Depret Grégoire , Van Bambeke Françoise , Tulkens Paul M , Prévost Martine
Published: March 2009

Background

P-glycoprotein belongs to the family of ATP-binding cassette proteins which hydrolyze ATP to catalyse the translocation of their substrates through membranes. This protein extrudes a large range of components out of cells, especially therapeutic agents causing a phenomenon known as multidrug resistance. Because of its clinical interest, its activity and transport function have been largely characterized by various biochemical studies. In the absence of a high-resolution structure of P-glycoprotein, homology modeling is a useful tool to help interpretation of experimental data and potentially guide experimental studies.

Results

We present here three-dimensional models of two different catalytic states of P-glycoprotein that were developed based on the crystal structures of two bacterial multidrug transporters. Our models are supported by a large body of biochemical data. Measured inter-residue distances correlate well with distances derived from cross-linking data. The nucleotide-free model features a large cavity detected in the protein core into which ligands of different size were successfully docked. The locations of docked ligands compare favorably with those suggested by drug binding site mutants.

Conclusion

Our models can interpret the effects of several mutants in the nucleotide-binding domains (NBDs), within the transmembrane domains (TMDs) or at the NBD:TMD interface. The docking results suggest that the protein has multiple binding sites in agreement with experimental evidence. The nucleotide-bound models are exploited to propose different pathways of signal transmission upon ATP binding/hydrolysis which could lead to the elaboration of conformational changes needed for substrate translocation. We identified a cluster of aromatic residues located at the interface between the NBD and the TMD in opposite halves of the molecule which may contribute to this signal transmission.

Our models may characterize different steps in the catalytic cycle and may be important tools to understand the structure-function relationship of P-glycoprotein.
Gamma-linolenic acid inhibits both tumour cell cycle progression and angiogenesis in the orthotopic C6 glioma model through changes in VEGF, Flt1, ERK1/2, MMP2, cyclin D1, pRb, p53 and p27 protein expression
Authors: Miyake Juliano Andreoli , Benadiba Marcel , Colquhoun Alison
Published: March 2009

Background

Gamma-linolenic acid is a known inhibitor of tumour cell proliferation and migration in both in vitro and in vivo conditions. The aim of the present study was to determine the mechanisms by which gamma-linolenic acid (GLA) osmotic pump infusion alters glioma cell proliferation, and whether it affects cell cycle control and angiogenesis in the C6 glioma in vivo.

Methods

Established C6 rat gliomas were treated for 14 days with 5 mM GLA in CSF or CSF alone. Tumour size was estimated, microvessel density (MVD) counted and protein and mRNA expression measured by immunohistochemistry, western blotting and RT-PCR.

Results

GLA caused a significant decrease in tumour size (75 ± 8.8%) and reduced MVD by 44 ± 5.4%. These changes were associated with reduced expression of vascular endothelial growth factor (VEGF) (71 ± 16%) and the VEGF receptor Flt1 (57 ± 5.8%) but not Flk1. Expression of ERK1/2 was also reduced by 27 ± 7.7% and 31 ± 8.7% respectively. mRNA expression of matrix metalloproteinase-2 (MMP2) was reduced by 35 ± 6.8% and zymography showed MMP2 proteolytic activity was reduced by 32 ± 8.5%. GLA altered the expression of several proteins involved in cell cycle control. pRb protein expression was decreased (62 ± 18%) while E2F1 remained unchanged. Cyclin D1 protein expression was increased by 42 ± 12% in the presence of GLA. The cyclin dependent kinase inhibitors p21 and p27 responded differently to GLA, p27 expression was increased (27 ± 7.3%) while p21 remained unchanged. The expression of p53 was increased (44 ± 16%) by GLA. Finally, the BrdU incorporation studies found a significant inhibition (32 ± 11%) of BrdU incorporation into the tumour in vivo.

Conclusion

Overall the findings reported in the present study lend further support to the potential of GLA as an inhibitor of glioma cell proliferation in vivo and show it has direct effects upon cell cycle control and angiogenesis. These effects involve changes in protein expression of VEGF, Flt1, ERK1, ERK2, MMP2, Cyclin D1, pRb, p53 and p27. Combination therapy using drugs with other, complementary targets and GLA could lead to gains in treatment efficacy in this notoriously difficult to treat tumour.
The impact of surfactant protein-A on ozone-induced changes in the mouse bronchoalveolar lavage proteome
Authors: Haque Rizwanul , Umstead Todd M , Freeman Willard M , Floros Joanna , Phelps David S
Published: March 2009

Background

Ozone is a major component of air pollution. Exposure to this powerful oxidizing agent can cause or exacerbate many lung conditions, especially those involving innate immunity. Surfactant protein-A (SP-A) plays many roles in innate immunity by participating directly in host defense as it exerts opsonin function, or indirectly via its ability to regulate alveolar macrophages and other innate immune cells. The mechanism(s) responsible for ozone-induced pathophysiology, while likely related to oxidative stress, are not well understood.

Methods

We employed 2-dimensional difference gel electrophoresis (2D-DIGE), a discovery proteomics approach, coupled with MALDI-ToF/ToF to compare the bronchoalveolar lavage (BAL) proteomes in wild type (WT) and SP-A knockout (KO) mice and to assess the impact of ozone or filtered air on the expression of BAL proteins. Using the PANTHER database and the published literature most identified proteins were placed into three functional groups.

Results

We identified 66 proteins and focused our analysis on these proteins. Many of them fell into three categories: defense and immunity; redox regulation; and protein metabolism, modification and chaperones. In response to the oxidative stress of acute ozone exposure (2 ppm; 3 hours) there were many significant changes in levels of expression of proteins in these groups. Most of the proteins in the redox group were decreased, the proteins involved in protein metabolism increased, and roughly equal numbers of increases and decreases were seen in the defense and immunity group. Responses between WT and KO mice were similar in many respects. However, the percent change was consistently greater in the KO mice and there were more changes that achieved statistical significance in the KO mice, with levels of expression in filtered air-exposed KO mice being closer to ozone-exposed WT mice than to filtered air-exposed WT mice.

Conclusion

We postulate that SP-A plays a role in reactive oxidant scavenging in WT mice and that its absence in the KO mice in the presence or absence of ozone exposure results in more pronounced, and presumably chronic, oxidative stress.
Resolution of tongue lesions caused by Leishmania infantum in a dog treated with the association miltefosine-allopurinol
Authors: Foglia Manzillo Valentina , Paparcone Rosa , Cappiello Silvia , De Santo Roberta , Bianciardi Paolo , Oliva Gaetano
Published: March 2009

Canine leishmaniosis is a severe systemic disease caused by the kinetoplastid protozoan Leishmania infantum, an obligatory intracellular parasite of mammalian macrophages, transmitted by the bite of phlebotomine sandflies. The infection in dogs might occur without any clinical signs or might be characterised by chronic viscerocutaneous signs, such as lymphadenopathy, skin lesions, splenomegaly, onychogryphosis, and renal as well as ocular damage due to immunocomplex deposition. In atypical cases the parasites can be found in the striated musculature, the central nervous system, the endocrine glands or gonads, with or without functional damage. Leishmania infection might seldom induce oral lesions, particularly on the tongue. The authors describe the clinical case of a four-year old mongrel dog with tongue lesions caused by L. infantum. The dog was presented due to diarrhoea, lack of appetite and hypersalivation. Examination of the oral cavity revealed the presence of multiple red, nodular lesions on the dorsal and lateral surfaces of the tongue. Definite diagnosis of an infection with L. infantum was obtained by an indirect immunofluorescence antibody test (IFAT) and by the cytological identification of the parasite in nodular, lingual lesions and bone marrow aspirates. The dog was treated with a combination of miltefosine (Milteforan®, Virbac), 2 mg/kg orally once a day for four weeks and allopurinol (Ziloric®, GlaxoSmithKline), 10 mg/kg orally twice a day for six months. At the end of the treatment, the animal showed full remission of clinical signs. The authors outline the atypical manifestations in the oral cavity in combination with a L. infantum infection and discuss the therapeutic potential of the combination treatment of miltefosine and allopurinol in canine leishmaniosis.
Quietism and Polemic
Authors: Chamberlain Lesley
Published: March 2009

Although they have a religious origin, the terms quietist and quietism have generally been used in the anglophone world in the context created by the French Revolution, which made them expressions of political abuse. Examination of classic instances of their use shows that in fact they were terms of psychological abuse, signs that men and women of political commitment could not understand, let alone accept, others who were not committed to one side or other in the revolutionary struggle. This paper takes issue with the egregious simplicity of that that attitude, while exploring aspects of the Idealist tradition in German philosophy which, also emerging from the challenge of the French Revolution, found positive terms and complex human explanations for behaviour that held back from definite political commitment. It concludes by suggesting the terms quietist and quietism have become redundant in a world that has moved on from a crude clash of revolution versus reaction.
The Humility of Hypocrisy
Authors: Isaacs Alick
Published: March 2009

Following directly upon an account of the author's personal experiences as a young soldier in Gaza during the course of the first intifada in 1987, this essay is an attempt to “cash in” rabbinic statements that present the entire Torah as a path to peace. The essay suggests that the genre of rabbinic debate—rather than the specific content of rabbinic statements—can be understood as peaceful. The study of halakhic literature, which is generally understood either as designed to clarify and quantify explicit legal demands or as a setting for pluralistic and progressive legal debate, is reevaluated with the purpose of limiting the potential of religious law to justify acts of violence. This reevaluation is founded upon an implicit critique of the “liberal” strategies that have sought to control the dangerous potential of religious law. The author proposes an irenic understanding of the halakha built upon partial and limited evaluations of the law's truth-claims. It argues that rabbinic debating generates multiple understandings for every detail of the law that entangle and conceal any ultimate sense of the law from view. The result is a legal system that is modest about its conclusions—and content to implement them partially—hypocritically. The religious value of such a system is that the truth claims of the law are thus modeled upon—and duplicate—the paradoxical opaqueness of prophetic revelation. Ultimately, this essay argues that this conception of the halakha is inherently tentative and hence peaceful.