bluuebunny/crossref_metadata_2025 huggingface dataset:
Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway
Authors: Du Jin-Xing , Sun Ming-Yu , Du Guang-Li , Li Feng-Hua , Liu Cheng , Mu Yong-Ping , Chen Gao-Feng , Long Ai-Hua , Bian Yan-Qin , Liu Jia , Liu Cheng-Hai , Hu Yi-Yang , Xu Lie-Ming , Liu Ping
Published: April 2012

Background

Huangqi decoction was first described in Prescriptions of the Bureau of Taiping People's Welfare Pharmacy in Song Dynasty (AD 1078), and it is an effective recipe that is usually used to treat consumptive disease, anorexia, and chronic liver diseases. Transforming growth factor beta 1 (TGFβ1) plays a key role in the progression of liver fibrosis, and Huangqi decoction and its ingredients (IHQD) markedly ameliorated hepatic fibrotic lesions induced by ligation of the common bile duct (BDL). However, the mechanism of IHQD on hepatic fibrotic lesions is not yet clear. The purpose of the present study is to elucidate the roles of TGFβ1 activation, Smad-signaling pathway, and extracellular signal-regulated kinase (ERK) in the pathogenesis of biliary fibrosis progression and the antifibrotic mechanism of IHQD.

Methods

A liver fibrosis model was induced by ligation of the common bile duct (BDL) in rats. Sham-operation was performed in control rats. The BDL rats were randomly divided into two groups: the BDL group and the IHQD group. IHQD was administrated intragastrically for 4 weeks. At the end of the fifth week after BDL, animals were sacrificed for sampling of blood serum and liver tissue. The effect of IHQD on the TGFβ1 signaling pathway was evaluated by western blotting and laser confocal microscopy.

Results

Decreased content of hepatic hydroxyproline and improved liver function and histopathology were observed in IHQD rats. Hepatocytes, cholangiocytes, and myofibroblasts in the cholestatic liver injury released TGFβ1, and activated TGFβ1 receptors can accelerate liver fibrosis. IHQD markedly inhibited the protein expression of TGFβ1, TGFβ1 receptors, Smad3, and p-ERK1/2 expression with no change of Smad7 expression.

Conclusion

IHQD exert significant therapeutic effects on BDL-induced fibrosis in rats through inhibition of the activation of TGFβ1-Smad3 and TGFβ1-ERK1/2 signaling pathways.
A histopathologic study of fatal paediatric cerebral malaria caused by mixed Plasmodium falciparum/Plasmodium vivax infections
Authors: Manning Laurens , Rosanas-Urgell Anna , Laman Moses , Edoni Henry , McLean Catriona , Mueller Ivo , Siba Peter , Davis Timothy ME
Published: April 2012

Microvascular sequestration of Plasmodium falciparum underlies cerebral malaria. Despite suggestive ex vivo evidence, this phenomenon has not been convincingly demonstrated in coma complicating Plasmodium vivax malaria. Severely-ill Papua New Guinean children with mixed P. falciparum/P. vivax infections are more likely to develop cerebral malaria and die than those with P. falciparum alone, possibly reflecting P. vivax sequestration. Nested PCR was performed on post mortem brain tissue from three such children dying from cerebral malaria due to mixed-species infections. No P. vivax DNA was detected. These findings do not support the hypothesis that P. vivax sequestration occurs in human brain.
Production and validation of a good manufacturing practice grade human fibroblast line for supporting human embryonic stem cell derivation and culture
Authors: Prathalingam Nilendran , Ferguson Linda , Young Lesley , Lietz Georg , Oldershaw Rachel , Healy Lyn , Craig Albert , Lister Helen , Binaykia Rakesh , Sheth Radhika , Murdoch Alison , Herbert Mary
Published: April 2012

Introduction

The development of reproducible methods for deriving human embryonic stem cell (hESC) lines in compliance with good manufacturing practice (GMP) is essential for the development of hESC-based therapies. Although significant progress has been made toward the development of chemically defined conditions for the maintenance and differentiation of hESCs, efficient derivation of new hESCs requires the use of fibroblast feeder cells. However, GMP-grade feeder cell lines validated for hESC derivation are not readily available.

Methods

We derived a fibroblast cell line (NclFed1A) from human foreskin in compliance with GMP standards. Consent was obtained to use the cells for the production of hESCs and to generate induced pluripotent stem cells (iPSCs). We compared the line with a variety of other cell lines for its ability to support derivation and self-renewal of hESCs.

Results

NclFed1A supports efficient rates (33%) of hESC colony formation after explantation of the inner cell mass (ICM) of human blastocysts. This compared favorably with two mouse embryonic fibroblast (MEF) cell lines. NclFed1A also compared favorably with commercially available foreskin fibroblasts and MEFs in promoting proliferation and pluripotency of a number of existing and widely used hESCs. The ability of NclFed1A to maintain self-renewal remained undiminished for up to 28 population doublings from the master cell bank.

Conclusions

The human fibroblast line Ncl1Fed1A, produced in compliance with GMP standards and qualified for derivation and maintenance of hESCs, is a useful resource for the advancement of progress toward hESC-based therapies in regenerative medicine.
Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-VII Study
Authors: Tveit Kjell Magne , Guren Tormod , Glimelius Bengt , Pfeiffer Per , Sorbye Halfdan , Pyrhonen Seppo , Sigurdsson Fridbjorn , Kure Elin , Ikdahl Tone , Skovlund Eva , Fokstuen Tone , Hansen Flemming , Hofsli Eva , Birkemeyer Elke , Johnsson Anders , Starkhammar Hans , Yilmaz Mette Karen , Keldsen Nina , Erdal Anne Berit , Dajani Olav , Dahl Olav , Christoffersen Thoralf
Published: April 2012

Purpose

The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated.

Patients and Methods

Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points.

Results

Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated.

Conclusion

Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.
Differential Expression of Wnt Signaling Molecules Between Pre- and Postmenopausal Endometrial Epithelial Cells Suggests a Population of Putative Epithelial Stem/Progenitor Cells Reside in the Basalis Layer
Authors: Nguyen Hong P. T. , Sprung Carl N. , Gargett Caroline E.
Published: April 2012

The human endometrium undergoes extensive monthly regeneration in response to fluctuating levels of circulating estrogen and progesterone in premenopausal (Pre-M) women. In contrast, postmenopausal (Post-M) endometrium is thin and quiescent with low mitotic activity, similar to the Pre-M endometrial basalis layer. Clonogenic epithelial stem/progenitor (ESP) cells, likely responsible for regenerating endometrial epithelium, have been identified in Pre-M and Post-M endometrium, but their location is unknown. We undertook transcriptional profiling of highly purified epithelial cells from full-thickness Pre-M and Post-M endometrium to identify differentially regulated genes that may indicate a putative ESP cell population resides in the basalis of Pre-M and basalis-like Post-M endometrium. Of 1077 differentially expressed genes identified, the Wnt signaling pathway, important in endometrial development and stem cell regulation, was one of the main gene families detected, including 22 Wnt-associated genes. Twelve genes were validated using quantitative RT-PCR, and all were concordant with microarray data. Immunostaining showed glandular epithelial location of Wnt-regulated genes, Axin-related protein 2 and β-catenin. Axin2 localized to the nucleus of basalis Pre-M and Post-M and cytoplasm of functionalis Pre-M endometrium, suggesting that it regulates β-catenin. Comparison of our Post-M gene profile with published gene microarray datasets revealed similarities to Pre-M basalis epithelial profiles. This differential expression of multiple Wnt-associated genes in human Pre-M and Post-M endometrial epithelial cells and the similar gene profile of Post-M and Pre-M basalis epithelium suggests that a population of putative endometrial ESP may reside in the basalis of Pre-M endometrium, which may be responsible for regenerating glandular epithelium each month.
Hepatocarcinogenesis in FXR−/− Mice Mimics Human HCC Progression That Operates through HNF1α Regulation of FXR Expression
Authors: Liu Nian , Meng Zhipeng , Lou Guiyu , Zhou Weiping , Wang Xiaoqiong , Zhang Yunfeng , Zhang Lisheng , Liu Xiyong , Yen Yun , Lai Lily , Forman Barry M. , Xu Zhonggao , Xu Rongzhen , Huang Wendong
Published: April 2012

Farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4) is a member of nuclear hormone receptor superfamily, which plays essential roles in metabolism of bile acids, lipid, and glucose. We previously showed spontaneously hepatocarcinogenesis in aged FXR−/− mice, but its relevance to human hepatocellular carcinoma (HCC) is unclear. Here, we report a systematical analysis of hepatocarcinogenesis in FXR−/− mice and FXR expression in human liver cancer. In this study, liver tissues obtained from FXR−/− and wild-type mice at different ages were compared by microarray gene profiling, histological staining, chemical analysis, and quantitative real-time PCR. Primary hepatic stellate cells and primary hepatocytes isolated from FXR−/− and wild-type mice were also analyzed and compared. The results showed that the altered genes in FXR−/− livers were mainly related to metabolism, inflammation, and fibrosis, which suggest that hepatocarcinogenesis in FXR−/− mice recapitulated the progression of human liver cancer. Indeed, FXR expression in human HCC was down-regulated compared with normal liver tissues. Furthermore, the proinflammatory cytokines, which were up-regulated in human HCC microenvironment, decreased FXR expression by inhibiting the transactivity of hepatic nuclear factor 1α on FXR gene promoter. Our study thereby demonstrates that the down-regulation of FXR has an important role in human hepatocarcinogenesis and FXR−/− mice provide a unique animal model for HCC study.
Talking Back to the Regents
Authors: Davis Octavia
Published: April 2012

Upon entering college composition courses, students often report a dislike for writing. Because researchers report that writing anxiety may be linked to high-stakes writing exams, a study of graduates of New York high schools was conducted to investigate whether the state's Regents Comprehensive Examination in English shapes attitudes or assumptions about writing. For this study, first-year writing students responded to a prompt that asked them to reconstruct an essay they wrote for the exam, as well as their feelings before, during, and after writing the essay. Evidence suggests that most students strongly dislike taking the exam. Preparing for and responding to it may impart lessons contradictory to objectives of many first-year writing programs. Most students report critical engagement with the test question but suppress critical commentary in their official responses so as to please the imagined graders, whom most students conflate with the specific audience posited by the question. The study indicates that open-form, experimental writing about standardized writing exams at the outset of the semester may help students transform resistance to writing from a general feeling to an attitude associated with a particular memory and, thus, may help clear the air for the work of college-level writing.
Transcriptional co-regulation of neuronal migration and laminar identity in the neocortex
Authors: Kwan Kenneth Y. , Šestan Nenad , Anton E. S.
Published: April 2012

The cerebral neocortex is segregated into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection (pyramidal) neurons and inhibitory interneurons. Development of the neocortex requires the orchestrated execution of a series of crucial processes, including the migration of young neurons into appropriate positions within the nascent neocortex, and the acquisition of layer-specific neuronal identities and axonal projections. Here, we discuss emerging evidence supporting the notion that the migration and final laminar positioning of cortical neurons are also co-regulated by cell type- and layer-specific transcription factors that play concomitant roles in determining the molecular identity and axonal connectivity of these neurons. These transcriptional programs thus provide direct links between the mechanisms controlling the laminar position and identity of cortical neurons.
Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors
Authors: Ninov Nikolay , Borius Maxim , Stainier Didier Y. R.
Published: April 2012

Genetic studies have implicated Notch signaling in the maintenance of pancreatic progenitors. However, how Notch signaling regulates the quiescent, proliferative or differentiation behaviors of pancreatic progenitors at the single-cell level remains unclear. Here, using single-cell genetic analyses and a new transgenic system that allows dynamic assessment of Notch signaling, we address how discrete levels of Notch signaling regulate the behavior of endocrine progenitors in the zebrafish intrapancreatic duct. We find that these progenitors experience different levels of Notch signaling, which in turn regulate distinct cellular outcomes. High levels of Notch signaling induce quiescence, whereas lower levels promote progenitor amplification. The sustained downregulation of Notch signaling triggers a multistep process that includes cell cycle entry and progenitor amplification prior to endocrine differentiation. Importantly, progenitor amplification and differentiation can be uncoupled by modulating the duration and/or extent of Notch signaling downregulation, indicating that these processes are triggered by distinct levels of Notch signaling. These data show that different levels of Notch signaling drive distinct behaviors in a progenitor population.
Loss of Llgl1 in retinal neuroepithelia reveals links between apical domain size, Notch activity and neurogenesis
Authors: Clark Brian S. , Cui Shuang , Miesfeld Joel B. , Klezovitch Olga , Vasioukhin Valeri , Link Brian A.
Published: April 2012

To gain insights into the cellular mechanisms of neurogenesis, we analyzed retinal neuroepithelia deficient for Llgl1, a protein implicated in apicobasal cell polarity, asymmetric cell division, cell shape and cell cycle exit. We found that vertebrate retinal neuroepithelia deficient for Llgl1 retained overt apicobasal polarity, but had expanded apical domains. Llgl1 retinal progenitors also had increased Notch activity and reduced rates of neurogenesis. Blocking Notch function by depleting Rbpj restored normal neurogenesis. Experimental expansion of the apical domain, through inhibition of Shroom3, also increased Notch activity and reduced neurogenesis. Significantly, in wild-type retina, neurogenic retinal progenitors had smaller apical domains compared with proliferative neuroepithelia. As nuclear position during interkinetic nuclear migration (IKNM) has been previously linked with cell cycle exit, we analyzed this phenomenon in cells depleted of Llgl1. We found that although IKNM was normal, the relationship between nuclear position and neurogenesis was shifted away from the apical surface, consistent with increased pro-proliferative and/or anti-neurogenic signals associated with the apical domain. These data, in conjunction with other findings, suggest that, in retinal neuroepithelia, the size of the apical domain modulates the strength of polarized signals that influence neurogenesis.
Pleiotrophin Expression during Odontogenesis
Authors: Erlandsen Heidi , Ames Jennifer E. , Tamkenath Amena , Mamaeva Olga , Stidham Katherine , Wilson Mary E. , Perez-Pinera Pablo , Deuel Thomas F. , MacDougall Mary
Published: April 2012

Pleiotrophin (PTN) is an extracellular matrix–associated growth factor and chemokine expressed in mesodermal and ectodermal cells. It plays an important role in osteoblast recruitment and differentiation. There is limited information currently available about PTN expression during odontoblast differentiation and tooth formation, and thus the authors aimed to establish the spatiotemporal expression pattern of PTN during mouse odontogenesis. Immortalized mouse dental pulp (MD10-D3, MD10-A11) and odontoblast-like (M06-G3) and ameloblast-like (EOE-3M) cell lines were grown and samples prepared for immunocytochemistry, Western blot, and conventional and quantitative PCR analysis. Effects of BMP2, BMP4, and BMP7 treatment on PTN expression in odontoblast-like M06-G3 cells were tested by quantitative PCR. Finally, immunohistochemistry of sectioned mice mandibles and maxillaries at developmental stages E16, E18, P1, P6, P10, and P28 was performed. The experiments showed that PTN, at both the mRNA and protein level, was expressed in all tested epithelial and mesenchymal dental cell lines and that the level of PTN mRNA was influenced differentially by the bone morphogenetic proteins. The authors observed initial expression of PTN in the inner enamel epithelium with prolonged expression in the ameloblasts and odontoblasts throughout their stages of maturation and strong expression in the terminally differentiated and enamel matrix–secreting ameloblasts and odontoblasts of the adult mouse incisors and molars.
Ovarian Abnormalities in a Mouse Model of Fragile X Primary Ovarian Insufficiency
Authors: Hoffman Gloria E. , Le Wei Wei , Entezam Ali , Otsuka Noriyuki , Tong Zhi-Bin , Nelson Lawrence , Flaws Jodi A. , McDonald John H. , Jafar Sanjeeda , Usdin Karen
Published: April 2012

FMR1 premutation (PM) alleles have 55–200 CGG·CCG-repeats in their 5′ UTR. PM carriers are at risk of fragile X–associated tremor and ataxia syndrome (FXTAS). Females are also at risk for FX primary ovarian insufficiency (FXPOI). PM pathology is generally attributed to deleterious properties of transcripts with long CGG-tracts. For FXPOI, hormone changes suggest a reduced residual follicle pool. Whether this is due to a smaller than normal original follicle pool or an increased rate of follicle depletion is unclear. A FX-PM mouse the authors generated with 130 CGG·CCG-repeats in the endogenous Fmr1 gene recapitulates features of FXTAS. Here the authors demonstrate that the gross development of the ovary and the establishment of the primordial follicle pool is normal in these mice. However, these animals show a faster loss of follicles of all follicle classes, suggesting that the problem is intrinsic to the ovary. In addition, many oocytes show aberrant nuclear accumulation of FMRP and elevated levels of ubiquitination. Furthermore, PM follicles are smaller and have fewer granulosa cells (GCs) than normal. Thus, these animals have ovarian abnormalities involving both the oocytes and GCs that may shed light on the molecular basis of FXPOI in humans.
Precipitation, soils, NPP, and biodiversity: resurrection of Albrecht's curve
Authors: Huston Michael A.
Published: April 2012

Climate and soils are widely recognized as major drivers of virtually all properties of ecosystems and communities. However, despite major advances in the understanding of soil formation and ecosystem dynamics, the effects of climate on soil properties are not widely appreciated. Understanding the effects of water availability on the rates of chemical and biological processes that affect soil formation can help clarify the global patterns of soil fertility, which affect agricultural and forest productivity, as well as biodiversity. Empirical tests of Albrecht's conceptual model of soil development and degradation using global climate and soil data sets and soil chronosequences confirm that soil total exchangeable bases (TEB), phosphorus, nitrogen, and other components of soil fertility, along with plant productivity generally decline on older soils and under wetter conditions as precipitation exceeds potential evapotranspiration. The basic pattern of soil fertility in relation to water availability is a unimodal curve, with a maximum near or below a water balance of zero (annual precipitation minus annual potential evapotranspiration). Analysis of global data by subregions reveals significant differences between temperate and tropical soil fertility distributions, as well as significant differences between continents. The low levels of soil nutrients (e.g., TEB, P, N) and plant productivity found on ancient soils or highly weathered soils in regions with high precipitation suggest that the positive effects of low productivity on plant diversity that have been observed at local and regional scales may also occur at the global scale.
Periodontal Status and Hyperlipidemia: Statin Users Versus Non‐Users
Authors: Sangwan Aditi , Tewari Shikha , Singh Harpreet , Sharma Rajinder K. , Narula Satish C.
Published: April 2012

Background: The association between serum lipids and periodontal disease has been studied predominantly in patients with chronic periodontitis with limited data available regarding periodontal status of patients with hyperlipidemia. Meanwhile, the impact of statins on the periodontal health of the population also remains largely underexplored. This study aims to assess the periodontal status among patients with hyperlipidemia and users of statins.

Methods: In this cross‐sectional study, 94 patients with hyperlipidemia (50 receiving statins and 44 receiving non‐pharmacologic therapy) and 46 control individuals who were normolipidemic underwent periodontal examination (plaque index, gingival index [GI], probing depth [PD], and clinical attachment level [CAL]). Biochemical parameters measured included serum triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL) cholesterol, and high‐density lipoprotein cholesterol levels.

Results: PD and GI were significantly higher in patients with hyperlipidemia who were non‐statin users compared with the normolipidemic individuals (P <0.001 [PD] and P <0.05 [GI]) and the statin group (P = 0.001 [PD] and P <0.05 [GI]). Periodontal parameters between statin users and the normolipidemic group did not differ significantly. After adjusting for confounders, positive and significant correlations were observed between PD and TG, and TC and LDL, whereas CAL shared correlation with TC and LDL. GI was correlated with TG and TC. Regression analyses revealed that whereas TC was associated significantly with PD (P <0.001), LDL showed significant association with CAL (P = 0.013). TG showed significant association with GI (P = 0.020).

Conclusions: Our findings suggest that relative to the general population, patients with hyperlipidemia are more prone to periodontal disease. Also, within the limits of this study, statins have a positive impact on periodontal health.
Global Perception, Meaning, and Aesthetic Appreciation
Authors: Moore Kathleen M. , West Alan N.
Published: April 2012

Studies show meaningfulness overshadows collative variables in determining aesthetic preferences, and this meaning effect can occur very quickly, requiring only very brief visual information. Observers can understand the gist of a natural scene in a glance, even when the images are blurred. By manipulating spatial frequencies, we varied the image resolution of Realist, Impressionist, Cubist, and Abstract Expressionist paintings, and asked participants with no artistic training to rate them on Meaning, Preference, Complexity, Unity and Variety (each subject saw one level of blur/clarity). No matter how blurred the images, Realist and Impressionist paintings were judged more preferable and meaningful than Cubist and Abstract Expressionist art, and within the former styles meaning was the best predictor of preferences. Results support Martindale's theory of cognitive hedonics, which ascribes aesthetic preference to the net activation of semantic modules.
Comparison of the effects of xylazine bolus versus medetomidine constant rate infusion on the stress response, urine production, and anesthetic recovery characteristics in horses anesthetized with isoflurane
Authors: Creighton Catherine M. , Lemke Kip A. , Lamont Leigh A. , Horney Barbara S. , Doyle Aimie J.
Published: April 2012

Objective—To compare the effect of xylazine bolus versus medetomidine constant rate infusion (MCRI) on serum cortisol and glucose concentrations, urine production, and anesthetic recovery characteristics in dorsally recumbent, spontaneously breathing, isoflurane-anesthetized horses.

Design—Prospective, randomized crossover study.

Animals—10 healthy Standardbreds.

Procedures—Horses were premedicated with xylazine or medetomidine IV. Anesthesia was induced with diazepam and ketamine and maintained with isoflurane for 150 minutes. For the xylazine treatment, end-tidal isoflurane concentration was maintained at 1.7% and xylazine (0.2 mg/kg [0.09 mg/lb]), IV) was administered as a bolus at the end of anesthesia. For the MCRI treatment, end-tidal isoflurane concentration was maintained at 1.4% and medetomidine (0.005 mg/kg/h [0.0023 mg/lb/h], IV) was infused throughout anesthesia. Serum cortisol and glucose concentrations were measured before, during, and after anesthesia. Urine specific gravity and volume were measured during anesthesia. Unassisted anesthetic recoveries were recorded by a digital video camera for later evaluation by 2 observers who were blinded to treatment.

Results—Serum cortisol concentration was lower and serum glucose concentration was higher with MCRI treatment, compared with xylazine treatment. Time to sternal recumbency was longer with MCRI treatment, but no difference was seen between treatments for times to extubation, first movement, or standing. Objective (mean attempt interval) and subjective (visual analog score) recovery scores were significantly better with MCRI treatment, compared with xylazine treatment.

Conclusions and Clinical Relevance—In isoflurane-anesthetized horses, premedication and administration of medetomidine as a constant rate infusion resulted in decreased serum cortisol concentration, increased serum glucose concentration, and superior anesthetic recovery characteristics, compared with conventional treatment with xylazine.
A Novel Marker of Human Endometrial Mesenchymal Stem-Like Cells
Authors: Masuda Hirotaka , Anwar Siti S. , Bühring Hans-Jörg , Rao Jyothsna R. , Gargett Caroline E.
Published: April 2012

Coexpression of CD140b (PDGFRβ) and CD146 has been used to isolate endometrial mesenchymal stem-like cells (eMSCs), which have a perivascular location. This study aims to evaluate a single marker for purifying eMSCs. Using an antibody panel with novel specificities, we screened human endometrial tissues and stromal cell suspensions by flow cytometry and immunohistochemistry to identify perivascular markers. Sorted subpopulations were examined for colony-forming unit (CFU), self-renewal, and differentiation assays for mesenchymal stem cell (MSC) function. We also transplanted sorted eMSCs under the kidney capsule of superimmunodeficient NSG mice. Magnetic bead selection was compared with flow cytometry sorting (flow sorting) using CFU assay. One novel marker (W5C5) was particularly effective in selecting eMSCs. W5C5+cells comprise 4.2 ± 0.6% ( n = 34) of endometrial stromal cells and reside predominantly in a perivascular location in both basal and functional layers of endometrium. The clonogenicity of W5C5+cells is significantly greater than W5C5-and unselected cells. W5C5+cells differentiated into adipocytes, osteocytes, chondrocytes, myocytes, and endothelial cells. W5C5+cells produce endometrial stromal-like tissue in vivo. In terms of clonogenicity, magnetic bead-selected W5C5+cells gave rise to significantly higher CFU numbers compared to flow-sorted W5C5+cells. This study identified W5C5 as a single marker capable of purifying eMSCs possessing MSC properties and reconstituting endometrial stromal tissues in vivo. W5C5 enriches eMSCs to high purity and provides a simple protocol for their prospective isolation using magnetic bead selection rather than flow sorting. W5C5 selection may provide an alternate, readily available autologous source of MSC, obtainable with minimal morbidity using an office endometrial biopsy procedure for future cell-based therapies.
Evidence of reduced arbuscular mycorrhizal fungal colonization in multiple lines of Bt maize
Authors: Cheeke Tanya E. , Rosenstiel Todd N. , Cruzan Mitchell B.
Published: April 2012

• Premise of the study: Insect‐resistant Bacillus thuringiensis (Bt) maize is widely cultivated, yet few studies have examined the interaction of symbiotic arbuscular mycorrhizal fungi (AMF) with different lines of Bt maize. As obligate symbionts, AMF may be sensitive to genetic changes within a plant host. Previous evaluations of the impact of Bt crops on AMF have been inconsistent, and because most studies were conducted under disparate experimental conditions, the results are difficult to compare.

• Methods: We evaluate AMF colonization in nine Bt maize lines, differing in number and type of engineered trait, and five corresponding near‐isogenic parental (P) base hybrids in greenhouse microcosms. Plants were grown in 50% local agricultural soil with low levels of fertilization, and AMF colonization was evaluated at 60 and 100 d. Nontarget effects of Bt cultivation on AMF colonization were tested in a subsequently planted crop, Glycine max, which was seeded into soil that had been preconditioned for 60 d with Bt or P maize.

• Key results: We found that Bt maize had lower levels of AMF colonization in their roots than did the non‐Bt parental lines. However, reductions in AMF colonization were not related to the expression of a particular Bt protein. There was no difference in AMF colonization in G. max grown in the Bt‐ or P‐preconditioned soil.

• Conclusions: These findings are the first demonstration of a reduction in AMF colonization in multiple Bt maize lines grown under the same experimental conditions and contribute to the growing body of knowledge examining the unanticipated effects of Bt crop cultivation on nontarget soil organisms.
Time Course of Peritoneal Function in Automated and Continuous Peritoneal Dialysis
Authors: Michels Wieneke M. , Verduijn Marion , Parikova Alena , Boeschoten Elisabeth W. , Struijk Dirk G. , Dekker Friedo W. , Krediet Raymond T.
Published: April 2012

♦ Background and Objectives

In automated peritoneal dialysis (APD), a patient's peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD—compared with that of CAPD—on peritoneal transport over 4 years.

♦ Design, Setting, Participants, and Measurements

Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start.

♦ Results

The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute ( p > 0.19) or fluid transport ( p > 0.13) were observed. Similarly, free water transport ( p = 0.43) and small-pore transport ( p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results.

♦ Conclusions

Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups.
Vieillir en beauté ? Transformations et pratiques corporelles des femmes
Authors: Macia Enguerran , Chevé Dominique
Published: April 2012

L’objectif de cet article est de décrire et de comprendre le vécu des transformations corporelles d’ordre esthétique chez les femmes âgées de 65 à 75 ans. Pour aborder cette problématique, 29 entretiens compréhensifs ont été réalisés à Marseille en 2011. Après un bref rappel des normes esthétiques occidentales contemporaines, nous détaillerons les marques du temps perçues comme stigmatisantes par les femmes et analyserons les pratiques corporelles destinées à les dissimuler ou à les réparer. La dernière partie de cet article sera consacrée au corps esthétique vécu et montrera notamment que le vieillissement peut, paradoxalement, avoir un effet bénéfique pour certaines femmes.
Kinematics Analysis of 6-DOF Parallel Micro-Manipulators with Offset U-Joints
Authors: Dalvand Mohsen Moradi , Shirinzadeh Bijan
Published: April 2012

This paper analyses the kinematics of a special 6-DOF parallel micro-manipulator with offset RR-joint configuration. Kinematics equations are derived and numerical methodologies to solve the inverse and forward kinematics are presented. The inverse and forward kinematics of such robots compared with those of 6-UCU parallel robots are more complicated due to the existence of offsets between joints of RR-pairs. The characteristics of RR-pairs used in this manipulator are investigated and kinematics constraints of these offset U-joints are mathematically explained in order to find the best initial guesses for the numerical solution. Both inverse and forward kinematics of the case study 6-DOF parallel micro-manipulator are modelled and computational analyses are performed to numerically verify accuracy and effectiveness of the proposed methodologies.
Secure e-Government Services
Authors: Karokola Geoffrey , Yngström Louise , Kowalski Stewart
Published: April 2012

E-Government offers many benefits to government agencies, citizens and the business community. However, e-Government services are prone to current and emerging security challenges posing potential threats to critical information assets. Securing it appears to be a major challenge facing governments globally. Based on the international security standards – the paper thoroughly investigates and analyzes eleven e-government maturity models (eGMMs) for security services. Further, it attempts to establish a common frame of reference for eGMM critical stages. The study utilizes the Soft Systems Methodology (SSM) of scientific inquiry/ learning cycle adopted from Checkland and Scholes. The findings show that security services (technical and non-technical) are lacking in eGMMs – implying that eGMMs were designed to measure more quantity of offered e-government services than the quality of security services. Therefore, as a step towards achieving secure e-government services the paper proposes a common frame of reference for eGMM with five critical stages. These stages will later be extended to include the required security services.
Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor
Authors: Kitamura Hidemitsu , Kobayashi Minoru , Wakita Daiko , Nishimura Takashi
Published: April 2012

Neurokinin A (NKA), a neurotransmitter distributed in the central and peripheral nervous system, strictly controls vital responses, such as airway contraction, by intracellular signaling through neurokinin-2 receptor (NK2R). However, the function of NKA–NK2R signaling on involvement in immune responses is less-well defined. We demonstrate that NK2R-mediated neuropeptide signaling activates dendritic cell (DC)-mediated type 1 immune responses. IFN-γ stimulation significantly induced NK2R mRNA and remarkably enhanced surface protein expression levels of bone marrow-derived DCs. In addition, the DC-mediated NKA production level was significantly elevated after IFN-γ stimulation in vivo and in vitro. We found that NKA treatment induced type 1 IFN mRNA expressions in DCs. Transduction of NK2R into DCs augmented the expression level of surface MHC class II and promoted Ag-specific IL-2 production by CD4+ T cells after NKA stimulation. Furthermore, blockade of NK2R by an antagonist significantly suppressed IFN-γ production by both CD4+ T and CD8+ T cells stimulated with the Ag-loaded DCs. Finally, we confirmed that stimulation with IFN-γ or TLR3 ligand (polyinosinic-polycytidylic acid) significantly induced both NK2R mRNA and surface protein expression of human PBMC-derived DCs, as well as enhanced human TAC1 mRNA, which encodes NKA and Substance P. Thus, these findings indicate that NK2R-dependent neuropeptide signaling regulates Ag-specific T cell responses via activation of DC function, suggesting that the NKA–NK2R cascade would be a promising target in chronic inflammation caused by excessive type 1-dominant immunity.
Trastuzumab for HER2-Positive Metastatic Breast Cancer: Clinical and Economic Considerations
Authors: Jeyakumar Alwin , Younis Tallal
Published: April 2012

Trastuzumab is a recombinant humanized monoclonal antibody that selectively targets the extra-cellular domain of the HER2 receptor. It was approved by the FDA in September 1998 as the first targeted therapy for HER2-positive metastatic breast cancer, and has since led to significant improvements in the overall prognosis for patients with HER2-positive metastatic disease. The favourable benefit/risk profile associated with palliative trastuzumab has been demonstrated in a number of clinical trials that examined trastusumab as monotherapy or in combination with chemotherapy, endocrine therapy and other HER2 targeted agents. The clinical benefits of trastuzumab, however should also be examined within the context of its significant drug acquisition costs. This review highlights the significant findings from the landmark clinical trials of trastuzumab for metastatic HER2-positive breast cancer, and the potential “value for money” associated with its use in clinical practice.
Particle mass yield from β-caryophyllene ozonolysis
Authors: Chen Q. , Li Y. L. , McKinney K. A. , Kuwata M. , Martin S. T.
Published: April 2012

Abstract. The influence of second-generation products on the particle mass yield of β-caryophyllene ozonolysis was systematically tested and quantified. The approach was to vary the relative concentrations of first- and second-generation products by adjusting the concentration of ozone while observing changes in particle mass yield. For all wall-loss corrected organic particle mass concentrations Morg of this study (0.5 < Morg < 230 μg m−3), the data show that the particle-phase organic material was composed for the most part of second-generation products. For 0.5< Morg < 10 μg m−3, a range which overlaps with atmospheric concentrations, the particle mass yield was 10 to 20% and was not sensitive to ozone exposure, implying that the constituent molecules were rapidly produced at all investigated ozone exposures. In contrast, for Morg > 10 μg m−3 the particle mass yield increased to as high as 70% for the ultimate yield corresponding to the greatest ozone exposures. These differing dependencies on ozone exposure under different regimes of Morg are explained by a combination of the ozonolysis lifetimes of the first-generation products and the volatility distribution of the resulting second-generation products. First-generation products that have short lifetimes produce low-volatility second-generation products whereas first-generation products that have long lifetimes produce high-volatility second-generation products. The ultimate particle mass yield was defined by mass-based stoichiometric yields αi of α0 = 0.17 ± 0.05, α1 = 0.11 ± 0.17, and α2 = 1.03 ± 0.30 for corresponding saturation concentrations of 1, 10, and 100 μg m−3. Terms α0 and α1 had low sensitivity to the investigated range of ozone exposure whereas term α2 increased from 0.32 ± 0.13 to 1.03 ± 0.30 as the ozone exposure was increased. These findings potentially allow for simplified yet accurate parameterizations in air quality and climate models that seek to represent the ozonolysis particle mass yields of certain classes of biogenic compounds.
3-D evaluation of tropospheric ozone simulations by an ensemble of regional Chemistry Transport Model
Authors: Zyryanov D. , Foret G. , Eremenko M. , Beekmann M. , Cammas J.-P. , D'Isidoro M. , Elbern H. , Flemming J. , Friese E. , Kioutsioutkis I. , Maurizi A. , Melas D. , Meleux F. , Menut L. , Moinat P. , Peuch V.-H. , Poupkou A. , Razinger M. , Schultz M. , Stein O. , Suttie A. M. , Valdebenito A. , Zerefos C. , Dufour G. , Bergametti G. , Flaud J.-M.
Published: April 2012

Abstract. A detailed 3-D evaluation of an ensemble of five regional Chemistry Transport Models (RCTM) and one global CTM with focus on free tropospheric ozone over Europe is presented. It is performed over a summer period (June to August 2008) in the context of the GEMS-RAQ project. A data set of about 400 vertical ozone profiles from balloon soundings and commercial aircraft at 11 different locations is used for model evaluation, in addition to satellite measurements with the infrared nadir sounder (IASI) showing largest sensitivity to free tropospheric ozone. In the middle troposphere, the four regional models using the same top and boundary conditions from IFS-MOZART exhibit a systematic negative bias with respect to observed profiles of about −20%. Root Mean Square Error (RMSE) values are constantly growing with altitude, from 22% to 32% to 53%, respectively for 0–2 km, 2–8 km and 8–10 km height ranges. Lowest correlation is found in the middle troposphere, with minimum coefficients (R) between 0.2 to 0.45 near 8 km, as compared to 0.7 near the surface and similar values around 10 km. A sensitivity test made with the CHIMERE mode also shows that using hourly instead of monthly chemical boundary conditions generally improves the model skill (i.e. improve RMSE and correlation). Lower tropospheric 0–6 km partial ozone columns derived from IASI show a clear North-South gradient over Europe, which is qualitatively reproduced by the models. Also the temporal variability showing decreasing ozone concentrations in the lower troposphere (0–6 km columns) during summer is well reproduced by models even if systematic bias remains (the value of the bias being also controlled by the type of used boundary conditions). A multi-day case study of a trough with low tropopause was conducted and showed that both IASI and models were able to resolve strong horizontal gradients of middle and upper tropospheric ozone occurring in the vicinity of an upper tropospheric frontal zone.
Brief communication "Importance of slope-induced error correction in volume change estimates from radar altimetry"
Authors: Hurkmans R. T. W. L. , Bamber J. L. , Griggs J. A.
Published: April 2012

Abstract. In deriving elevation change rates (dH/dt) from radar altimetry, the slope-induced error is usually assumed to cancel out in repeat measurements. These measurements, however, represent a location that can be significantly further upslope than assumed, causing an underestimate of the basin-integrated volume change. In a case-study for the fast-flowing part of Jakobshavn Isbræ, we show that a relatively straightforward correction for slope-induced error increases elevation change rates by up to several metres per year and significantly reduces the volume change error with respect to laser altimetry for the area of interest.
A Study on Hand Contamination and Hand Washing Practices among Medical Students
Authors: De Alwis Watutantrige Ranjit , Pakirisamy Premalatha , Wai San Lum , Xiaofen Evelyn Chen
Published: April 2012

Harmful microorganisms can be transferred to hands from contaminated surfaces people come into contact in daily life. Contaminated hands can transmit disease to one self as well as to others. A study was done to determine the extent to which hand hygiene practices and toilet door knobs contribute to the bacterial load of hands of toilet users in a medical school. Swabs were taken from a randomly selected sample of 60 medical students for bacterial count from both hands before and after toilet use and from door knobs of six toilets. Only 40 (66.7%) claimed they washed hands with soap. Significantly more females (83%) used soap to wash hands compared to males (50%). Bacterial load in the hands of both males and females showed an increase after toilet use. The increase was significant among male students. The dominant hand had a significantly higher bacterial load than the other. The mean bacterial load of male toilet door knobs (12 CFU/cm2) were significantly higher than of female toilet door knobs (2.5 CFU/cm2) (P<0.05). Staphylococcus aureus was isolated from the hands of 21 students. Toilets and washrooms should be designed so as to eliminate the sources of contamination of the hands.
Sex Variability in Pediatric Leukemia Survival: Large Cohort Evidence
Authors: Holmes L. , Hossain J. , desVignes-Kendrick M. , Opara F.
Published: April 2012

Purpose. Sex disparities in pediatric leukemia have been previously reported, and male children continue to present with poorer survival. However, the observed disparities are not fully understood. This current study sought to examine disparities in survival by the sex, and to determine if tumor prognostic factors impact on these disparities. Patients and Methods. We used the Surveillance Epidemiology and End Results dataset of pediatric leukemia patients (ages 0–19 years) diagnosed in the United States from 1973 to 2006. There were 15,215 patients of whom 8,622 (65.7%) were boys and 6,593 (43.3%) were girls. The Kaplan-Meier survival estimates, log rank test, and Cox proportional hazard methods were used to assess the data. Results. The overall (both sexes) five-year survival rate was 67.9%. Girls had a survival rate of 70.1%, while the rate was 66.3% in boys. Girls had a significant 14% decreased risk of dying relative to boys, hazard ratio (HR) = 0.86, 99% CI = 0.80–0.93. There were significant differences between boys and girls with respect to tumor cell type, race, age at diagnosis, year of diagnosis, and number of primaries, P<0.001. After controlling for these factors, the sex differences in survival persisted, with girls still less likely to die from leukemia compared to boys, adjusted HR (AHR) = 0.85, 99% CI = 0.72–1.00, P<0.01. Conclusion. In a large population-based pediatric leukemia study, boys continued to show poorer survival. These disparities were not completely explained by treatment received, tumor prognostic or socio-demographic factors.