bluuebunny/crossref_metadata_2025 huggingface dataset:
A MICROSIMULATION EVALUATION OF EFFICIENCY, INEQUALITY, AND POLARIZATION EFFECTS OF IMPLEMENTING THE DANISH, THE FRENCH, AND THE U.K. REDISTRIBUTION SYSTEM IN SPAIN
Authors: Oliver Xisco , Piccoli Luca , Spadaro Amedeo
Published: December 2009

This paper provides evidence about the effects of possible reforms of the Spanish direct redistribution system. We perform an ex‐ante evaluation of the impact upon efficiency, income distribution, and polarization of the replacement of the Spanish system with the ones enforced in France, the U.K., and Denmark (corporatist, liberal, and social‐democratic model respectively). The analysis is performed using microsimulation models in which labor supply is explicitly taken into account. The results show that the simulated scenarios have little impact on the efficiency of the economy. We find that each of the new systems would reduce income inequality. However, when we take into consideration income polarization, the effects of the reforms are ambiguous: in some cases we observe a tendency toward an increased polarization.
Post‐Fire Control of Invasive Plants Promotes Native Recovery in a Burned Desert Shrubland
Authors: Steers Robert J. , Allen Edith B.
Published: December 2009

Invasive annual grasses have become increasingly important components of desert vegetation in North America. They are especially problematic because they increase the extent, severity, and frequency of fire in desert shrublands that normally experience fire very rarely, or not at all. After fire, invasive grasses and forbs are often dominant and restoration methods are required to promote native plant recovery. Three treatments to control invasive annual grasses and forbs were implemented in the first 3 years following a fire in creosote bush scrub vegetation. Treatments included early season mechanical removal (raking) of all annuals, grass‐specific herbicide (Fusilade II), and Fusilade II plus hand pulling of exotic forbs. In the first year, all treatments reduced invasive annual grass abundance by about half but had little effect on native annuals. Treatment effectiveness was minimal in the first year due to low and irregular distribution of rainfall. In the second year, insufficient rainfall prevented the germination of any annual plants and no treatments were applied. In the third year, precipitation onset occurred later in the season and was above average. Although the raking treatment performed poorly, treatments utilizing Fusilade II nearly eliminated invasive grasses and forbs, achieved native annual dominance, and increased native perennial abundance. These results indicate that in the absence of invasive grasses and forbs, the native annual community can be resilient to fire disturbance and native perennials can recover. The results also suggest that burned creosote bush shrublands can be managed after fire to decrease the chance of invasive plant–fire feedback.
Spatio‐Temporal Relationship between Water Depletion and Root Distribution Patterns of Centaurea solstitialis and Two Native Perennials
Authors: Young Stephen L. , Kyser Guy B. , Barney Jacob N. , Claassen Victor P. , DiTomaso Joseph M.
Published: December 2009

In a 2‐year field study, we quantified lateral root growth patterns and soil water depletion dynamics in the invasive annual Centaurea solstitialis and two native perennials, Elymus glaucus and Grindelia camporum. Centaurea solstitialis produced lateral roots most actively from early April to mid‐June, during the late rosette to spiny seedhead stage while both root growth and water depletion were completed before flowering. In the wet year, roots were evenly distributed throughout the soil profile to 180 cm deep. Lack of deep soil moisture recharge in the second year restricted root distribution to shallow soil depths (< 60 cm). In contrast to C. solstitialis, living roots of the native perennials persisted throughout the year. Elymus glaucus roots were most abundant (47% of total roots) in the upper soil profile (≤ 60 cm) in the wet year, but most abundant (55%) in the lower profile (≥ 150 cm) in the dry year. However, the distribution of G. camporum roots was comparable between the 2 years. This indicates that in years with little to no deep soil moisture recharge, C. solstitialis roots are distributed in the shallow soil profile similar to annual grasses, whereas in wetter years it is similar to deep‐rooted perennial species. We also show that C. solstitialis impacts grassland communities by depleting soil moisture during the short period of lateral root growth from the late rosette to the spiny stage. Therefore, control of C. solstitialis early in the season is critical during native plant restoration where success depends upon available soil moisture.
Function of platelets in apheresis platelet concentrates and in patient blood after transfusion as assessed by Impact‐R
Authors: Horvath Michaela , Eichelberger Beate , Koren Daniela , Böhm Alexandra , Ay Cihan , Jilma Bernd , Panzer Simon , Jilma‐Stohlawetz Petra
Published: December 2009

BACKGROUND: Platelet (PLT) transfusion is a mainstream therapy for preventing or treating bleeding episodes in patients with thrombocytopenia. The efficacy is usually estimated from the corrected count increment of PLTs after transfusion, which does not assess PLT function. We therefore evaluated PLT function in blood samples of patients with thrombocytopenia before and after transfusion.

STUDY DESIGN AND METHODS: PLT function was assessed in 24 chemotherapy‐treated patients and in the PLT concentrates (PCs) by the Impact‐R (DiaMed). This device evaluates PLT adhesion and aggregation recorded as surface coverage (%) and size of aggregates (AS µm2). P‐selectin expression was determined by flow cytometry.

RESULTS: The PCs were stored for a median of 70 hours before transfusion. An analysis stratified by the median storage of PCs (<70 hr or >70 hr) showed no differences in the SC, the AS, and P‐selectin expression between these concentrates' groups. Transfusion resulted in an increase of adhering PLTs in the patients after transfusion. There were no differences in the AS and in P‐selectin expression before and after transfusion, but the AS increased after transfusion upon ex vivo exposure to adenosine 5′‐diphosphate. P‐selectin expression was significantly lower in the patient group receiving PCs stored for more than 70 hours.

CONCLUSION: The current trial shows the feasibility of using the Impact‐R to assess the function of transfused PLTs in the patient's blood stream.
Piperacillin‐induced immune hemolysis: new cases and a concise review of the literature
Authors: Mayer Beate , Yürek Salih , Salama Abdulgabar
Published: December 2009

BACKGROUND: In this study, the data of eight new patients in conjunction with previously reported cases with piperacillin‐induced immune hemolytic anemia (PIHA) are described.

STUDY DESIGN AND METHODS: Five patients with cystic fibrosis and three patients with other disorders developed massive hemolysis after administration of piperacillin. Serologic tests were carried out using standard techniques. Tests for drug‐dependent antibodies (ddab) were performed in the presence and absence of piperacillin and its ex vivo antigens (urine of patients treated with piperacillin).

RESULTS: Hemolysis was acute and severe in all eight patients. The direct antiglobulin test was positive in all cases. Sera from four patients reacted with red blood cells (RBCs) in the presence of piperacillin as well as its ex vivo antigens. Sera from three patients showed positive reactivity with untreated RBCs in the presence of piperacillin, and the serum from the remaining patient was reactive only in the presence of piperacillin ex vivo antigens. Other patients with PIHA have been reported in the literature. Three of these patients also had cystic fibrosis.

CONCLUSION: To date approximately 26 patients with PIHA have been described and at least eight of these patients had cystic fibrosis. It is unclear whether patients with cystic fibrosis might be susceptible in developing PIHA.
Immunoglobulin M red blood cell alloantibodies are frequently adsorbed by rabbit erythrocyte stroma
Authors: Yuan Shan , Fang Amy , Davis Rebecca , Siplon Christopher J. , Goldfinger Dennis
Published: December 2009

BACKGROUND: Rabbit erythrocyte stroma (RESt, Immucor) adsorption is often used to remove cold autoantibodies from patient samples to facilitate detection of underlying alloantibodies. However, reports in the literature show that adsorption of clinically significant alloantibodies can occur. A 2006 study by Storry and colleagues suggested that immunoglobulin (Ig)M antibodies are adsorbed by RESt regardless of antigen specificity. In our study, we further investigated the adsorption of IgM red blood cell alloantibodies by RESt.

STUDY DESIGN AND METHODS: A total of 12 sera containing monoclonal IgM antibodies of various specificities (anti‐ D, ‐C, ‐c, ‐E, ‐e, ‐K, ‐Jkb, and ‐S) and titers, which were all shown to exhibit only IgM reactivity after dithiothreitol treatment, and two sera with polyclonal IgG (anti‐Fya and ‐K) were all adsorbed by RESt. Titers of unadsorbed, once‐adsorbed, and twice‐adsorbed IgM and IgG antibodies were determined in parallel.

RESULTS: Ten of the 12 monoclonal IgM samples showed significant (more than fourfold) reduction in titer after RESt adsorptions. Both of the polyclonal IgG samples tested showed insignificant (fourfold or less) reduction in titer.

CONCLUSIONS: RESt is known to effectively remove IgM cold autoantibodies. Our results show that monoclonal IgM alloantibodies are also frequently adsorbed by RESt with significant reduction in titer. Adsorption is variable and some IgM alloantibodies are not adsorbed. Further studies may elucidate the effect of RESt adsorption on IgG alloantibodies. Caution is needed when RESt is employed to remove interferences by cold autoantibodies in pretransfusion testing, and the risk of missed IgM alloantibodies must be considered.
Preharvest hematopoietic progenitor cell counts predict CD34+ cell yields in granulocyte–colony‐stimulating factor–mobilized peripheral blood stem cell harvest in healthy donors
Authors: Yang Shang‐Hsien , Wang Tso‐Fu , Tsai His‐Hsiu , Lin Teng‐Yi , Wen Shu‐Hui , Chen Shu‐Huey
Published: December 2009

BACKGROUND: The hematopoietic progenitor cell (HPC) count measured by the Sysmex hematology analyzer can determine the timing for leukapheresis in autologous peripheral blood stem cell (PBSC) harvest. We evaluated whether a HPC count could predict CD34+ cell yield in healthy, unrelated donors after granulocyte–colony‐stimulating factor mobilization.

STUDY DESIGN AND METHODS: A total of 117 healthy donors underwent 161 PBSC leukapheresis procedures in our institution. The HPCs and CD34+ cells were identified by an automated hematology analyzer and flow cytometry, respectively. Using Spearman's rank test, we evaluated the relationships between preharvest HPCs, CD34+ cell counts, and CD34+ cell yields in the apheresis product. A receiver operating characteristic (ROC) curve analysis was used to identify the cutoff value of HPC for adequate mobilization and harvest yield.

RESULTS: The HPC count had a moderate correlation with the preharvest CD34+ cell count (r = 0.502, p < 0.001), and an HPC count of more than 21.3 × 106/L could exclude poor mobilization (<20 × 106 CD34+ cells/L) with sensitivity and specificity of 89.2 and 83.3%. However, the relationship between HPC count and CD34+ cell yield was not marked (r = 0.321, p < 0.001). The area under the curve for HPCs was significantly smaller than the preharvest CD34+ cell count on the ROC curve for predicting adequate harvest yield (>10 × 106 CD34+ cells/L of processed blood volume, 0.678 vs. 0.850, p = 0.001).

CONCLUSION: Although the preapheresis HPC count could predict mobilization in healthy donors before leukapheresis, it may not be a superior index for predicting CD34+ cell yield compared with the preharvest CD34+ cell count.
Removal by adsorbent beads of biological response modifiers released from platelets, accumulated during storage, and potentially associated with platelet transfusion reactions
Authors: Tanaka Shigenori , Hayashi Tomoya , Tani Yoshihiko , Hirayama Fumiya
Published: December 2009

BACKGROUND: Recent studies have demonstrated that biological response modifiers (BRMs) released from platelets (PLTs) during storage may have a clinical significance in PLT transfusion reactions. Washing PLTs and partial substitution of plasma with artificial solutions reduce transfusion reactions, but the washing procedure is time‐consuming, and partial plasma substitution is not sufficient to completely eliminate transfusion reactions.

STUDY DESIGN AND METHODS: This study determined the levels of three BRMs: soluble CD40 ligand (sCD40L); regulated upon activation, normal T‐cell expressed, and secreted (RANTES, CCL5); and transforming growth factor‐β1 (TGF‐β1). These BRMs were released from PLTs during storage up to Day 10. To selectively remove these BRMs, four types of cellulose beads were investigated. The levels of these three BRMs in plasma derived from PLT concentrates (PCs) stored for 10 days or in PCs stored for 5 days were determined after treatment with or without each adsorbent bead for 3 hours.

RESULTS: These three BRMs accumulated in proportion to the storage duration. The 3‐hour treatment with cellulose beads possessing sulfate ester groups (A) or phosphate ester groups (B) effectively removed sCD40L and RANTES and partly removed TGF‐β1. In addition, although PLT activation was minimally induced, PLT counts decreased by approximately 13% to 30%, after these treatments.

CONCLUSIONS: This study revealed that Cellulose Beads A or B are effective in removing the three BRMs that accumulate during PLT storage. Additional in vitro assays and in vivo studies are required to evaluate whether this method is effective in reducing transfusion reactions.
Consensus recommendations of pediatric transfusion medicine objectives for clinical pathology residency training programs
Authors: Sanchez Rosa , Sloan Steven R. , Josephson Cassandra D. , Ambruso Daniel R. , Hillyer Christopher D. , O'Sullivan Patricia
Published: December 2009

BACKGROUND: Pediatric transfusion medicine (PTM) is a subspecialty of transfusion medicine with no formal training program and few specialists. The Pediatric Transfusion Medicine Academic Awardees (PedsTMAA) group surveyed PTM content experts to identify relevant objectives for the first formal PTM curriculum.

STUDY DESIGN AND METHODS: Eight North American PTM experts were invited to participate in a two‐step consensus process. PTM‐related objectives compiled from a review of existing training documents were organized into a survey. Experts were asked to rate each objective for relevancy for a clinical pathology trainee. Content validity indexes (CVIs) and asymmetric confidence intervals (ACIs) of expert ratings and analysis of respondents' comments were used to identify relevant objectives.

RESULTS: Six experts participated and reviewed 117 objectives. Based on content validity criteria (CVI ≥ 0.83 and lower‐limit 95% ACI ≥ 3), a total of 65 objectives were considered relevant. Twenty‐three objectives were rated “very relevant” by all the experts while some proposed objectives were determined to be not relevant, out of date, or inappropriate for a resident trainee level.

CONCLUSIONS: The PedsTMAA group identified 65 objectives for a PTM curriculum. Twenty‐three represent a clear core set of objectives and should be considered for clinical pathology training. The next step is to consider the teaching strategies and evaluation methods that will be employed to best deliver this content addressing competency in medical knowledge.
West Nile virus in 2006 and 2007: the Canadian Blood Services' experience
Authors: O'Brien Sheila F. , Scalia Vito , Zuber Edna , Hawes Gordon , Alport Edward C. , Goldman Mindy , Fearon Margaret A.
Published: December 2009

BACKGROUND: The Canadian blood supply has been screened for West Nile virus (WNV) since 2003. A strategy for targeted individual‐donation nucleic acid testing (ID‐NAT) was implemented in 2004 to identify potentially infectious donations that may be missed by minipool (MP) testing. In 2007, Canada experienced a larger epidemic than in previous years providing an opportunity to evaluate the ID‐NAT triggering algorithm in higher‐risk areas.

STUDY DESIGN AND METHODS: A specially created database and internal‐external communication identified regions for targeted ID‐NAT using MP and community triggers. WNV‐positive donations identified by ID‐NAT were reexamined in MP to assess the efficacy of targeted ID‐NAT in identifying potentially infectious donations that may have been missed by MP testing. WNV‐positive donation data from 2006 and 2007 were analyzed to examine temporal and geographic trends. A telephone survey about symptoms was carried out after the 2007 season.

RESULTS: In total 78 WNV‐positive donations were identified (66 true‐positives and four false‐positives being in 2007). Most positive donations were in the late summer, concentrated in the same western provinces as community cases. Fifty‐two donations were identified by ID‐NAT and 46% were consistently positive in MP. Of the other 54%, 74% were immunoglobulin (Ig)M‐ and/or IgG‐positive. Fifty‐six percent of donors experienced mostly mild symptoms before or after donation (but all said they were well at the time of donation).

CONCLUSION: WNV‐positive donations correspond geographically with the epidemic. MP testing identifies most potentially infectious donations with a smaller potential benefit from targeted ID‐NAT. Mild symptoms are common but may not deter donation.
Photo‐Induced Effect in Heavy Metal Oxide Glasses
Authors: Heo Jong , Quan Chengzhe
Published: December 2009

Photo‐induced phenomena in binary (PbO–Ga2O3) and ternary (PbO–Bi2O3–Ga2O3) heavy metal oxide glasses were investigated. A red shift up to ∼0.05 eV in the absorption edge of 75PbO–25Ga2O3 glass (mol%) was observed by illuminating the subbandgap light for 30 min. This shift was completely erased by the heat treatment near the glass transition temperature. Refractive index of the glass at 600 nm also increased ∼0.011 by the illumination. It is believed that the presence of lone‐pair electrons associated with Pb‐polyhedra is essential to realize a reversible photo‐induced effect in these oxide glasses.
Rigid confocal endoscopy for in vivo imaging of experimental oral squamous intra‐epithelial lesions
Authors: Farahati Behnaz , Stachs Oliver , Prall Friedrich , Stave Joachim , Guthoff Rudolf , Pau Hans Wilhelm , Just Tino
Published: December 2009

J Oral Pathol Med (2010) 39: 318–327

Background:  A rigid confocal endoscope has been developed to assess the oral squamous epithelium of mice and to determine sensitivity, specificity, and accuracy of this new technology.

Methods:  This endoscope is connected to the commercially available Heidelberg Retina Tomograph (HRT). HRT is a device with a 670‐nm diode laser designed to acquire topographical measurements of the optic nerve head. Real‐time rigid confocal endoscopy is demonstrated by imaging the epithelial lesions of a mice model. Six‐week‐old male C57Bl/6 mice were randomly divided into a non‐treated group (n = 10) and into a 4‐nitroquinoline 1‐oxide (4‐NQO)‐treated group (n = 50). In the 4‐NQO‐treated group, the mice obtained 4‐nitroquinoline 1‐oxide in the drinking water (100 μg/ml) to induce tumourigenesis in the mouse tongue. The 4‐NQO‐solution was diluted in the drinking water for mice. After an 8–16‐week carcinogen treatment with 4‐NQO (ad libitum), mouse tongues were dissected within 3 h after CO2 overdose. After confocal microscopy of all lesions of the tongue, conventional histopathological investigation was performed.

Results:  The inter‐rater reliability for the two observers of the confocal microscopic findings was found to be Kappa = 0.59 (P < 0.001). The penetration depth varied in the healthy tissue of the underside of the tongue throughout this study and was measured between 104 and 240 μm. In keratotic lesions, the penetration depths were diminished and varied between 80 and 140 μm. Strong keratinization inhibits the evaluation of the epithelium. For differentiation between low‐grade and high‐grade squamous intra‐epithelial lesions, a sensitivity and specificity of 73% and 88% was reached.

Conclusions:  The animal experiment with this non‐invasive new technology indicates that this imaging technology facilitates the detection of pre‐cancerous lesions of the underside of the oropharynx. Human studies on oropharyngeal and laryngeal lesions are needed to prove the applicability of this method in the field of otorhinolaryngology.
Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma
Authors: Kim Yong‐Hun , Kim Soung‐Min , Kim Yu‐Kyoung , Hong Sam‐Pyo , Kim Myung‐Jin , Myoung Hoon
Published: December 2009

J Oral Pathol Med (2010) 39: 368–375

Background:  Poor prognosis of oral squamous cell carcinoma (OSCC) is partly attributed to the lack of significant tumor marker for accurate staging and prognostication. We have evaluated survivin, which is a member of the inhibitor of apoptosis family as a cancer marker associated with proliferation, angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a prognostic significance of survivin expression in lymph node previously.

Methods:  To evaluate survivin expression in six OSCC cell lines, Western blotting was performed. Hamster oral carcinogenesis model was used to observe changes of survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic and prognostic significance of survivin in a series of 38 primary OSCC through immunohistochemistry (CD31, PCNA) and Kaplan–Meier’s test.

Results:  Survivin expression was detected in all OSCC cell lines at a varying level but not observed in normal gingival keratinocyte cells. In hamster model, survivin expression was observed from 8 weeks through 16 weeks and the intensity of expression became strong until 16 weeks. Clinicopathological analysis revealed a significant correlation between survivin expression and lymph node metastasis (P = 0.006) and proliferation (P < 0.001). However, there was no significant relationship with differentiation, micro vessel density, and cancer stage based on TNM. Survivin overexpression had a significant negative effect on survival of patients.

Conclusions:  These results demonstrate the significant relationship between survivin expression and oral carcinogenesis and aggressiveness of OSCC including survival rate of patient. Survivin therefore may be used as a significant cancer marker to gain prognostic information of OSCC.
Erythrochelin – a hydroxamate‐type siderophore predicted from the genome of Saccharopolyspora erythraea
Authors: Robbel Lars , Knappe Thomas A. , Linne Uwe , Xie Xiulan , Marahiel Mohamed A.
Published: December 2009

The class of nonribosomally assembled siderophores encompasses a multitude of structurally diverse natural products. The genome of the erythromycin‐producing strain Saccharopolyspora erythraea contains 25 secondary metabolite gene clusters that are mostly considered to be orphan, including two that are responsible for siderophore assembly. In the present study, we report the isolation and structural elucidation of the hydroxamate‐type tetrapeptide siderophore erythrochelin, the first nonribosomal peptide synthetase‐derived natural product of S. erythraea. In an attempt to substitute the traditional activity assay‐guided isolation of novel secondary metabolites, we have employed a dedicated radio‐LC‐MS methodology to identify nonribosomal peptides of cryptic gene clusters in the industrially relevant strain. This methodology was based on transcriptome data and adenylation domain specificity prediction and resulted in the detection of a radiolabeled ornithine‐inheriting hydroxamate‐type siderophore. The improvement of siderophore production enabled the elucidation of the overall structure via NMR and MSn analysis and hydrolysate‐derivatization for the determination of the amino acid configuration. The sequence of the tetrapeptide siderophore erythrochelin was determined to be d‐α‐N‐acetyl‐δ‐N‐acetyl‐δ‐N‐hydroxyornithine‐d‐serine‐cyclo(l‐δ‐N‐hydroxyornithine‐l‐δ‐N‐acetyl‐δ‐N‐hydroxyornithine). The results derived from the structural and functional characterization of erythrochelin enabled the proposal of a biosynthetic pathway. In this model, the tetrapeptide is assembled by the nonribosomal peptide synthetase EtcD, involving unusual initiation‐ and cyclorelease‐mechanisms.
RMI1 deficiency in mice protects from diet and genetic‐induced obesity
Authors: Suwa Akira , Yoshino Masayasu , Yamazaki Chihiro , Naitou Masanori , Fujikawa Rie , Matsumoto Shun‐ichiro , Kurama Takeshi , Shimokawa Teruhiko , Aramori Ichiro
Published: December 2009

The aim of this study is to discover and characterize novel energy homeostasis‐related molecules. We screened stock mouse embryonic stem cells established using the exchangeable gene trap method, and examined the effects of deficiency of the target gene on diet and genetic‐induced obesity. The mutant strain 0283, which has an insertion at the recQ‐mediated genome instability 1 (RMI1) locus, possesses a number of striking features that allow it to resist metabolic abnormalities. Reduced RMI1 expression, lower fasting‐blood glucose and a reduced body weight (normal diet) were observed in the mutant mice. When fed a high‐fat diet, the mutant mice were resistant to obesity, and also showed improved glucose intolerance and reduced abdominal fat tissue mass and food intake. In addition, the mutants were also resistant to obesity induced by the lethal yellow agouti (Ay) gene. Endogenous RMI1 genes were found to be up‐regulated in the liver and adipose tissue of KK‐Ay mice. RMI1 is a component of the Bloom’s syndrome gene helicase complex that maintains genome integrity and activates cell‐cycle checkpoint machinery. Interestingly, diet‐induced expression of E2F8 mRNA, which is an important cell cycle‐related molecule, was suppressed in the mutant mice. These results suggest that the regulation of energy balance by RMI1 is attributable to the regulation of food intake and E2F8 expression in adipose tissue. Taken together, these findings demonstrate that RMI1 is a novel molecule that regulates energy homeostasis.
3T3‐L1 adipocyte apoptosis induced by thiazolidinediones is peroxisome proliferator‐activated receptor‐γ‐dependent and mediated by the caspase‐3‐dependent apoptotic pathway
Authors: Xiao Yuanyuan , Yuan Taichang , Yao Wenqi , Liao Kan
Published: December 2009

Although thiazolidinediones (TZDs) are potent promoters of adipogenesis in the preadipocyte, they induce apoptosis in several other cell types, such as cancer cells, endothelial cells and T‐lymphocytes. In this study, we investigated the proapoptotic effect of TZDs in mature 3T3‐L1 adipocytes, which express high levels of the peroxisome proliferator‐activated receptor‐γ (PPARγ) protein. Apoptosis was induced in mature 3T3‐L1 adipocytes by treatment with troglitazone, pioglitazone or prostaglandin J2, and could be blocked by the PPARγ antagonist GW9662. Treatment with PPARγ agonists also decreased Akt‐1 protein and phosphorylation levels without affecting phosphoinositide 3‐kinase and PTEN. Further analysis indicated that in troglitazone‐treated 3T3‐L1 adipocytes, Bad phosphorylation and Bcl‐2 protein levels were reduced, and Bax translocation to the mitochondria was increased. Subsequently, cytochrome c release and caspase‐3 cleavage were observed. TZD‐induced adipocyte apoptosis could be blocked by the caspase‐3 inhibitor Ac‐DEVD‐CHO or by overexpression of Bcl2. In cultured rat primary adipocytes, similar apoptosis‐inducing effects of troglitazone were also observed. Thus, TZDs promote apoptosis in adipocytes through a PPARγ‐dependent pathway. This apoptosis is mediated by the inhibition of Akt‐1, which decreases Bad phosphorylation and activates the mitochondrial apoptotic pathway.
Comparing the substrate specificities of cytochrome c biogenesis Systems I and II
Authors: Goddard Alan D. , Stevens Julie M. , Rondelet Arnaud , Nomerotskaia Elena , Allen James W. A. , Ferguson Stuart J.
Published: December 2009

c‐Type cytochromes require specific post‐translational protein systems, which vary in different organisms, for the characteristic covalent attachment of heme to the cytochrome polypeptide. Cytochrome c biogenesis System II, found in chloroplasts and many bacteria, comprises four subunits, two of which (ResB and ResC) are the minimal functional unit. The ycf5 gene from Helicobacter pylori encodes a fusion of ResB and ResC. Heterologous expression of ResBC in Escherichia coli lacking its own biogenesis machinery allowed us to investigate the substrate specificity of System II. ResBC is able to attach heme to monoheme c‐type cytochromes c550 from Paracoccus denitrificans and c552 from Hydrogenobacter thermophilus, both normally matured by System I. The production of holocytochrome is enhanced by the addition of exogenous reductant. Single‐cysteine variants of these cytochromes were not efficiently matured by System II, but System I was able to produce detectable amounts of AXXCH variants; this adds to evidence that there is no obligate requirement for a disulfide‐bonded intermediate for the latter c‐type cytochrome biogenesis system. In addition, System II was able to mature an AXXAH‐containing variant into a b‐type cytochrome, with implications for both heme supply to the periplasm and substrate recognition by System II.
Crystal structure of salt‐tolerant glutaminase from Micrococcus luteus K‐3 in the presence and absence of its product l‐glutamate and its activator Tris
Authors: Yoshimune Kazuaki , Shirakihara Yasuo , Wakayama Mamoru , Yumoto Isao
Published: December 2009

Glutaminase from Micrococcus luteus K‐3 [Micrococcus glutaminase (Mglu); 456 amino acid residues (aa); 48 kDa] is a salt‐tolerant enzyme. Our previous study determined the structure of its major 42‐kDa fragment. Here, using new crystallization conditions, we determined the structures of the intact enzyme in the presence and absence of its product l‐glutamate and its activator Tris, which activates the enzyme by sixfold. With the exception of a ‘lid’ part (26‐29 aa) and a few other short stretches, the structures were all very similar over the entire polypeptide chain. However, the presence of the ligands significantly reduced the length of the disordered regions: 41 aa in the unliganded structure (N), 21 aa for l‐glutamate (G), 8 aa for Tris (T) and 6 aa for both l‐glutamate and Tris (TG). l‐Glutamate was identified in both the G and TG structures, whereas Tris was only identified in the TG structure. Comparison of the glutamate‐binding site between Mglu and salt‐labile glutaminase (YbgJ) from Bacillus subtilis showed significantly smaller structural changes of the protein part in Mglu. A comparison of the substrate‐binding pocket of Mglu, which is highly specific for l‐glutamine, with that of Erwinia carotovora asparaginase, which has substrates other than l‐glutamine, shows that Mglu has a larger substrate‐binding pocket that prevents the binding of l‐asparagine with proper interactions.

Structured digital abstract

MINT‐7305730: Mglu (uniprotkb:Q4U1A6) and Mglu (uniprotkb:Q4U1A6) bind (MI:0407) by x‐ray crystallography (MI:0114)
Survey of the incidence and distribution of viruses infecting yam (Dioscorea spp.) in Ghana and Togo
Authors: Eni A.O. , Hughes J.d'A. , Asiedu R. , Rey M.E.C.
Published: December 2009

Yam leaves were collected during surveys of major yam producing agro‐ecological zones (AEZs) in Ghana (n = 628) and Togo (n = 218) respectively, in 2005. Leaf tissues were tested for Cucumber mosaic virus (CMV), Dioscorea mottle virus (DMoV), Yam mild mosaic virus (YMMV), Yam mosaic virus (YMV) and badnaviruses by enzyme‐linked immunosorbent assay (ELISA), immunocapture‐polymerase chain reaction (IC‐PCR) and/or IC‐reverse transcription‐PCR (IC‐RT‐PCR). Eighty‐one percent (370/459) and 78.9% (127/161) of symptomatic leaf samples from Ghana and Togo, respectively and 56.2% (95/169) and 57.9% (33/57) of non‐symptomatic leaf samples, reacted positive to CMV, YMMV, YMV and/or badnaviruses, but DMoV was not detected. The highest incidence of YMV and badnaviruses was observed in the forest–savannah transition and Guinea savannah AEZ respectively in Ghana. In Togo, incidence of badnaviruses across the four AEZ ranged from 50 to 57.9%; however, Savane Derivée Seche AEZ had the highest incidence of badnaviruses (57.9%), YMV (34.2%) and CMV (7.9%). Mixed infection of badnaviruses and YMMV was the most frequent (105 of 276 mixed infections) in the two countries and Dioscorea alata was more heavily infected than D. rotundata in both countries.
Absence management and presenteeism: the pressures on employees to attend work and the impact of attendance on performance
Authors: Baker‐McClearn Denise , Greasley Kay , Dale Jeremy , Griffith Frances
Published: December 2009

Absenteeism is an issue that has grown in importance over the past few years; however, little has been done to explore the impact of presenteeism on individual and organisational performance and well‐being. This article is based on interviews collected in nine case study organisations in the UK. Two sector organisations (one private and one public) were studied to examine absence management and a conceptual model of presenteeism, with further illustration provided using data from the other seven case studies. This enabled a pattern of presenteeism to emerge, along with the contextual and individual factors which impact on it. In addition to previous research, we found that presenteeism is a complex ‘problem’ and that it is not a single one‐dimensional construct, but is continually being shaped by individual and organisational factors. In addition, we found that performance and well‐being are more closely related to the organisational reaction to presenteeism and absenteeism, rather than the act itself.
Exploring alternative relationships between perceived investment in employee development, perceived supervisor support and employee outcomes
Authors: Kuvaas Bård , Dysvik Anders
Published: December 2009

The purpose of this study was to explore alternative relationships between perceived investment in employee development (PIED), perceived supervisor support (PSS), and employee outcomes in the form of attitudes (affective commitment and turnover intention) and work performance (work effort, work quality and organisational citizenship behaviour). A cross‐sectional survey among 331 employees from a Norwegian telecommunications organisation showed that the relationship between PSS and employee attitudes was partially mediated by PIED. In addition, PSS was found to moderate the relationship between PIED and three self‐report measures of work performance. The form of the moderation revealed a positive relationship only for high levels of PSS. These findings suggest that line managers are of vital importance in implementing developmental HR practices, either because they influence how such practices are perceived by employees, which, in turn, affects employee attitudes, or because positive experiences with both line managers and HR practices seem to be needed in order for developmental HR practices to positively influence employee performance.
Bacterial genotoxicity bioreporters
Authors: Biran Alva , Yagur‐Kroll Sharon , Pedahzur Rami , Buchinger Sebastian , Reifferscheid Georg , Ben‐Yoav Hadar , Shacham‐Diamand Yosi , Belkin Shimshon
Published: December 2009

Ever since the introduction of theSalmonella typhimuriummammalian microsome mutagenicity assay (the ‘Ames test’) over three decades ago, there has been a constant development of additional genotoxicity assays based upon the use of genetically engineered microorganisms. Such assays rely either on reversion principles similar to those of the Ames test, or on promoter–reporter fusions that generate a quantifiable dose‐dependent signal in the presence of potential DNA damaging compounds and the induction of repair mechanisms; the latter group is the subject of the present review. Some of these assays were only briefly described in the scientific literature, whereas others have been developed all the way to commercial products. Out of these, only one, theumu‐test, has been fully validated and ISO‐ and OECD standardized. Here we review the main directions undertaken in the construction and testing of bacterial‐based genotoxicity bioassays, including the attempts to incorporate at least a partial metabolic activation capacity into the molecular design. We list the genetic modifications introduced into the tester strains, compare the performance of the different assays, and briefly describe the first attempts to incorporate such bacterial reporters into actual genotoxicity testing devices.
Compositional breast imaging using a dual‐energy mammography protocol
Authors: Laidevant Aurelie D. , Malkov Serghei , Flowers Chris I. , Kerlikowske Karla , Shepherd John A.
Published: December 2009

Purpose

Mammography has a low sensitivity in dense breasts due to low contrast between malignant and normal tissue confounded by the predominant water density of the breast. Water is found in both adipose and fibroglandular tissue and constitutes most of the mass of a breast. However, significant protein mass is mainly found in the fibroglandular tissue where most cancers originate. If the protein compartment in a mammogram could be imaged without the influence of water, the sensitivity and specificity of the mammogram may be improved. This article describes a novel approach to dual‐energy mammography, full‐field digital compositional mammography (FFDCM), which can independently image the three compositional components of breast tissue: water, lipid, and protein.

Methods

Dual‐energy attenuation and breast shape measures are used together to solve for the three compositional thicknesses. Dual‐energy measurements were performed on breast‐mimicking phantoms using a full‐field digital mammography unit. The phantoms were made of materials shown to have similar x‐ray attenuation properties of the compositional compartments. They were made of two main stacks of thicknesses around 2 and 4 cm. Twenty‐six thickness and composition combinations were used to derive the compositional calibration using a least‐squares fitting approach.

Results

Very high accuracy was achieved with a simple cubic fitting function with root mean square errors of 0.023, 0.011, and 0.012 cm for the water, lipid, and protein thicknesses, respectively. The repeatability (percent coefficient of variation) of these measures was tested using sequential images and was found to be 0.5%, 0.5%, and 3.3% for water, lipid, and protein, respectively. However, swapping the location of the two stacks of the phantom on the imaging plate introduced further errors showing the need for more complete system uniformity corrections. Finally, a preliminary breast image is presented of each of the compositional compartments separately.

Conclusions

FFDCM has been derived and exhibited good compositional thickness accuracy on phantoms. Preliminary breast images demonstrated the feasibility of creating individual compositional diagnostic images in a clinical environment.
Commissioning of the discrete spot scanning proton beam delivery system at the University of Texas M.D. Anderson Cancer Center, Proton Therapy Center, Houston
Authors: Gillin Michael T. , Sahoo Narayan , Bues Martin , Ciangaru George , Sawakuchi Gabriel , Poenisch Falk , Arjomandy Bijan , Martin Craig , Titt Uwe , Suzuki Kazumichi , Smith Alfred R. , Zhu X. Ronald
Published: December 2009

Purpose

To describe a summary of the clinical commissioning of the discrete spot scanning proton beam at the Proton Therapy Center, Houston (PTC‐H).

Methods

Discrete spot scanning system is composed of a delivery system (Hitachi ProBeat), an electronic medical record (Mosaiq V 1.5), and a treatment planning system (TPS) (Eclipse V 8.1). Discrete proton pencil beams (spots) are used to deposit dose spot by spot and layer by layer for the proton distal ranges spanning from and over a maximum scan area at the isocenter of . An arbitrarily chosen reference calibration condition has been selected to define the monitor units (MUs). Using radiochromic film and ion chambers, the authors have measured spot positions, the spot sizes in air, depth dose curves, and profiles for proton beams with various energies in water, and studied the linearity of the dose monitors. In addition to dosimetric measurements and TPS modeling, significant efforts were spent in testing information flow and recovery of the delivery system from treatment interruptions.

Results

The main dose monitors have been adjusted such that a specific amount of charge is collected in the monitor chamber corresponding to a single MU, following the IAEA TRS 398 protocol under a specific reference condition. The dose monitor calibration method is based on the absolute dose per MU, which is equivalent to the absolute dose per particle, the approach used by other scanning beam institutions. The full width at half maximum for the spot size in air varies from approximately for for . The measured versus requested 90% depth dose in water agrees to within over ranges of . The beam delivery interlocks perform as expected, guarantying the safe and accurate delivery of the planned dose.

Conclusions

The dosimetric parameters of the discrete spot scanning proton beam have been measured as part of the clinical commissioning program, and the machine is found to function in a safe manner, making it suitable for patient treatment.
Detection of longitudinal lung structural and functional changes after diagnosis of radiation‐induced lung injury using hyperpolarized magnetic resonance imaging
Authors: Mathew Lindsay , Gaede Stewart , Wheatley Andrew , Etemad‐Rezai Roya , Rodrigues George B. , Parraga Grace
Published: December 2009

Purpose

Therapeutic radiation doses for thoracic tumors are significantly restricted to decrease the risk of nontumor tissue damage, yet radiation‐induced lung injury (RILI) still occurs in over of thoracic radiation treatment cases. Although RILI can be clinically monitored using pulmonary function measurements, the regional functional effects of the injury are not well understood. Hyperpolarized magnetic resonance imaging provides measurements of regional lung function and structure with high spatial and temporal resolution; the authors use this tool longitudinally for the first time in seven subjects after clinical diagnosis of RILI in order to better understand regional changes in lung function and structure post‐RILI.

Methods

All subjects underwent spirometry, plethysmography, and MRI at after radiation therapy commenced. Thoracic , static ventilation, and diffusion‐weighted images were acquired to generate the apparent diffusion coefficient (ADC) and percent ventilated volume (PVV). Four subjects returned after baseline imaging for follow‐up spirometry and MRI measurements of ADC and PVV.

Results

At baseline, PVV was significantly different and lower in the ipsilateral diseased lung compared to the contralateral nondiseased lung . Longitudinally, significant increases were observed for MRI PVV (, ) and MRI ADC (, ) in the contralateral lung only, in the four subjects who returned for follow‐up, while no changes in the ipsilateral lung were reported.

Conclusions

Hyperpolarized MRI was well tolerated in all subjects with moderate to severe RILI. Functional improvements and microstructural changes were observed in the contralateral lung, while the ipsilateral lung remained stable, suggesting that functional compensatory changes may have occurred in the contralateral lung due to ipsilateral lung radiation‐induced injury.
A BPF‐FBP tandem algorithm for image reconstruction in reverse helical cone‐beam CT
Authors: Cho Seungryong , Xia Dan , Pellizzari Charles A. , Pan Xiaochuan
Published: December 2009

Purpose

Reverse helical cone‐beam computed tomography (CBCT) is a scanning configuration for potential applications in image‐guided radiation therapy in which an accurate anatomic image of the patient is needed for image‐guidance procedures. The authors previously developed an algorithm for image reconstruction from nontruncated data of an object that is completely within the reverse helix. The purpose of this work is to develop an image reconstruction approach for reverse helical CBCT of a long object that extends out of the reverse helix and therefore constitutes data truncation.

Methods

The proposed approach comprises of two reconstruction steps. In the first step, a chord‐based backprojection‐filtration (BPF) algorithm reconstructs a volumetric image of an object from the original cone‐beam data. Because there exists a chordless region in the middle of the reverse helix, the image obtained in the first step contains an unreconstructed central‐gap region. In the second step, the gap region is reconstructed by use of a Pack–Noo‐formula‐based filteredbackprojection (FBP) algorithm from the modified cone‐beam data obtained by subtracting from the original cone‐beam data the reprojection of the image reconstructed in the first step.

Results

The authors have performed numerical studies to validate the proposed approach in image reconstruction from reverse helical cone‐beam data. The results confirm that the proposed approach can reconstruct accurate images of a long object without suffering from data‐truncation artifacts or cone‐angle artifacts.

Conclusions

They developed and validated a BPF‐FBP tandem algorithm to reconstruct images of a long object from reverse helical cone‐beam data. The chord‐based BPF algorithm was utilized for converting the long‐object problem into a short‐object problem. The proposed approach is applicable to other scanning configurations such as reduced circular sinusoidal trajectories.
On the scattering power of radiotherapy protons
Authors: Gottschalk Bernard
Published: December 2009

Purpose

First, to show that accurate formulas for scattering power must take into account the competition between the Gaussian core and the single scattering tail of the angular distribution, which affects the rate of change in the Gaussian width and leads to the single scattering correction (SSC). Second, to show that the SSC requires that be nonlocal: Besides material properties and energy at the point of interest, it must depend in some fashion on how much multiple scattering has already taken place. Third, after reviewing five previous formulas (three local and two nonlocal), to derive an improved “differential Molière” formula . Last, to investigate, by studying some practical cases, when an accurate formula for is actually needed.

Methods

We first take the numerical derivative of the Molière/Fano/Hanson in order to find the true SSC. We simplify the formula for (ICRU Report 35) for protons, introducing a new material dependent property, the “scattering length” , analogous to radiation length . We then use as a basis for by including a nonlocal correction factor which, by virtue of the Øverås approximation, parametrizes the single scattering correction.

Results

The improved scattering power is where , (MeV) is the initial product of proton momentum and speed, is the same at the point of interest, and . is easily computed and generalizes readily to mixed slabs because is not material dependent.

Conclusions

Whether an accurate formula for is required depends very much on the problem at hand. For beam spreading in water, five of the six formulas for give almost identical results, suggesting that patient dose calculations are insensitive to . That is not true, however, of beam spreading in Pb. At the opposite extreme, the projected rms beam width at the end of a Pb/Lexan/air stack, analogous to the upstream modulator in a passive beam spreading system, is sensitive to . In this case a simple experiment would discriminate between all but two of the six formulas discussed. Scattering power applies as much to Monte Carlo as to deterministic transport calculations. Using in any of its forms will avoid step size dependence. Using the best available could be important in general purpose Monte Carlo codes, which are expected to give the correct answer to many different problems.