bluuebunny/crossref_metadata_2025 huggingface dataset:
Provision of Support Strategies and Services
Authors: Bignell Whitney E. , Sullivan Elizabeth , Andrianos Anne , Anderson Alex Kojo
Published: January 2012

This study examined the determinants of support strategies and services provided by community-based breastfeeding counselors (CBBCs) and compared differences in extent of support provided by paid and volunteer counselors. Participants (N = 847) in this internet-based survey were mostly White/Caucasian (74.9%), college-educated (59.0%), and paid CBBCs (63.8%). The majority (75.9%) of volunteer CBBCs compared with their paid full-time (52.1%) and paid part-time (47.4%) counterparts had completed college. Being a full-time paid compared with volunteer/unpaid CBBC was associated with face-to-face counseling (OR = 3.69; 95% CI: 1.93, 7.06), use of client-centered counseling skills (OR = 6.23; 95% CI: 3.40, 11.45), making referrals to social service agencies (OR = 13.18; 95% CI: 6.86, 25.32), and helping position baby (OR = 3.77; 95% CI: 1.64, 8.69). Because of the disparities in CBBC usage of breastfeeding support strategies and continuing education between paid and volunteer CBBCs, there is a need to examine differences in training curricula and determine the facilitators and barriers of continuing education.
Development and Piloting of an Instrument That Measures Company Support for Breastfeeding
Authors: Hojnacki Sarah E. , Bolton Tracie , Fulmer Ingrid S. , Olson Beth H.
Published: January 2012

Background: Maternal employment has been cited as a barrier to continued breastfeeding, yet there have been few studies identifying company breastfeeding support.

Objectives: The study objectives were to develop and pilot an instrument that measures formal breastfeeding support in companies.

Methods: A survey of company breastfeeding supports was developed, based on the literature and expert review, and the survey piloted with Michigan-based companies.

Results: Completion of the surveys and open-ended comments indicated survey items were generally well understood. In the study sample (N = 151), significantly more support was offered in companies having more employees as compared to fewer, and in companies from the health care versus all other sectors ( P < .01). More support was also found in companies reporting requests for support, upper management combining breastfeeding and work, and a population that they felt likely to require breastfeeding support ( P < .01). Few companies (3%) had written policies on breastfeeding or pumping at work. However, the majority of companies allow women to pump milk at the worksite (94%), and provide time (73%) and nonrestroom space to pump (78%). Fewer companies allow breastfeeding at the company (22%) or designate a room solely for breastfeeding or pumping (32%).

Conclusions: The survey instrument is appropriate to determine breastfeeding supports in companies. In Michigan, larger companies and those in the health care sector provide more supports, most companies provide some type of space and time to pump, but other supports are limited.
Self-excited vibration of workpieces in a turning process
Authors: Han Xianguo , Ouyang Huajiang , Wang Minjie , Hassan Nurhafizzah , Mao Yuming
Published: January 2012

Vibration occurring during machining is a major limitation to the productivity and quality of products. The dynamic interaction between the cutter and the workpiece during a turning process causes self-excited vibration. If the level of vibration is sufficiently high, poor surface quality of the workpiece and excessive tool wear can occur. This article presents a dynamic model for the vibration in turning operations taking into account the time-dependent reduction of workpiece diameter and the regenerative chatter mechanism. The workpiece is modelled as a beam rotating about its longitudinal axis and the cutter provides a moving load that is a source of parametric excitation. Simulated numerical examples are presented. Turning experiments are conducted that demonstrate vibration and chatter in turning operations. It is found through comparison between the theoretical and numerical results that the established dynamic model can predict the vibration pattern of the workpieces fairly well but underestimates the magnitude of workpiece oscillation.
Precise signed digraph modelling based on causal dependence identification
Authors: Huang Xinlin , Gao Jianmin , Gao Zhiyong
Published: January 2012

The fault diagnosis approach based on signed digraph is promising, but signed digraph models built by existing methods often contain false causalities and make spurious diagnosis results. In this article, a signed digraph modelling method based on causal dependence identification is proposed. Many equations used to describe mechanism of process system can be used to analyse the cause–effect relation between state variables and build precise signed digraph models. The cause–effect relation hided in system equations is extracted through causal dependence identification of algebraic and differential equations. Signed digraph model is then constructed by merging the analysis results. The method of causal dependence identification and strongly connected components identification of process system is investigated in detail. Algorithm of causal dependence identification is summarized and results in a simple but effective signed digraph construction procedure. The validity of the proposed method was tested by the case study of signed digraph modelling for a series connected liquid storage system, and the efficiency of the algorithm was tested by another case study of a compressor unit system. The comparison result shows that the proposed method can extract precise causal dependence relation between state variables from system equations and build signed digraph model effectively with less resource consumption, which is very important for building signed digraph model of large scale process system.
Multivariate approach for protein identification based on mass spectrometric data
Authors: Lee Jung Bok , Lee Jae Won
Published: January 2012

Protein mass spectrometry provides a powerful tool for detecting and identifying proteins. Several database searching algorithms may be used for this purpose. However, most of them depend on the heuristic approaches and the use of probability-based or statistical approach was very restrictive in the current algorithms. In this study, we present a statistical modelling of scores based on a generalized linear mixed model and provide a feasible computation method using penalized generalized weighted least squares. This model incorporates the dependency among matches into a new statistical scoring function, and uses the beta-binomial distribution to derive the score. Based on simulation experiments and analysis using real examples, we have improved protein searching performance and provided feasible computation procedures to deal with very large datasets. In particular, our methods may significantly increase accuracy in identifying medium and small proteins.
Simulation in International Studies
Authors: Boyer Mark A.
Published: January 2012

Social scientists have long worked to replicate real-world phenomena in their research and teaching environments. Unlike our biophysical science colleagues, we are faced with an area of study that is not governed by the laws of physics and other more predictable relationships. As a result, social scientists, and international studies scholars more specifically here, must make use of simulation and experimentation to study and replicate social phenomena. Growing out of the increasing use of simulation in the international studies field, the following symposium is an excellent collection of articles that demonstrate the diversity of approaches to the use of simulation in international studies scholarship and approaches to learning.
World Music Ensemble
Authors: Beegle Amy C.
Published: January 2012

As instrumental world music ensembles such as steel pan, mariachi, gamelan and West African drums are becoming more the norm than the exception in North American school music programs, there are other world music ensembles just starting to gain popularity in particular parts of the United States. The kulintang ensemble, a drum and gong ensemble that originated in the Philippines, is one example of such an ensemble. Kulintang ensembles are easily accessible to general music students because of the percussion instrumentation and repetitive patterns of melodic contour. Such ensembles may be particularly successful in areas with large Filipino American populations.
Growing as a Professional Music Educator
Authors: Hesterman Phillip K.
Published: January 2012

Education is a lifelong adventure that is ever-changing and active. Educators continually adapt their practices to meet the needs of an ever-changing population of children flowing through the schools. It is advantageous for teachers to be committed to lifelong learning for their own professional and personal development. As a novice teacher becomes more adept in the profession, new reflections and new perspectives can bring into focus additional ways to improve one’s teaching, classroom demeanor, and the like. Professional interactions with other teachers are important for the music teacher to facilitate a dialogue for growth for the music teacher. Teachers who are learners throughout their careers realize that they are not the source of all knowledge pertaining to music. Good teaching practices are defined according to current educational thought, especially when the educator incorporates learner analysis and reflection into teaching and not only the acquisition of knowledge and imitation.
Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success
Authors: Greenberg Benjamin M , Graves Donna , Remington Gina , Hardeman Paula , Mann Martha , Karandikar Nitin , Stuve Olaf , Monson Nancy , Frohman Elliot
Published: January 2012

Background:

Neuromyelitis optica (NMO) is an autoimmune condition that predominantly causes severe optic neuritis and transverse myelitis. Rituximab therapy has dramatically improved patient care, but standardized dosing regimens and guidelines are lacking.

Objectives:

The objective of this study was to define a rituximab dosing strategy for NMO patients that achieves the lowest rate of relapses.

Methods:

This was a retrospective chart review of patients treated with various doses of rituximab.

Results:

Combining data from the NMO and multiple sclerosis (MS) patients, identified that the mean number of days after a 100 mg dose of rituximab until the CD19 population was greater than 2% was 99 days (standard deviation 36, range 43–172). When allowed to rise, the mean number of days after a 1000 mg dose of rituximab until the CD19 population was greater than 2% was 184 (standard deviation 72, range 52–288). The median number of days until a CD19 percentage of 2% was achieved was 133 days in the 100 mg dosing arm and 259 days in the 1000 mg dosing arm. Analysis of the survival curves via both the Mantel–Cox log-rank test and the Wilcoxon test determined that the difference between medial survival for 100 and 1000 mg doses was statistically significant with p-values <0.0001.

Conclusions:

Low doses of rituximab have a high rate of early B-cell repopulation. Any NMO patient treated with rituximab should be followed with monthly CD19 counts in order to identify the rare, but clinically significant, early repopulators.
Leak detection in gas pipelines using wavelet-based filtering
Authors: Urbanek J , Barszcz T , Uhl T , Staszewski WJ , Beck SBM , Schmidt B
Published: January 2012

The article presents the application of the wavelet filter for detection of leaks in gas pipelines. The idea behind the method is based on the detection of echoes reflected from turbulences induced by a leak. Such echoes are often very hard to detect, mainly due to high noise levels. The common way of enhancing the analysis is to apply a filter. Different types of filters can be used in practice. The selection of the appropriate filter type and its parameters is the major difficulty. The wavelet-based filter, selected for leakage detection, is optimally tuned using maximum values of kurtosis. The proposed method is verified using simulated and experimental signals with high noise levels. The results demonstrate that for the conditions used, the approach is superior over existing signal processing techniques. The method allows not only for leakage detection but also for leakage location and estimation of its severity.
Robot-Assisted Gait Training in Patients With Parkinson Disease
Authors: Picelli Alessandro , Melotti Camilla , Origano Francesca , Waldner Andreas , Fiaschi Antonio , Santilli Valter , Smania Nicola
Published: January 2012

Background. Gait impairment is a common cause of disability in Parkinson disease (PD). Electromechanical devices to assist stepping have been suggested as a potential intervention. Objective. To evaluate whether a rehabilitation program of robot-assisted gait training (RAGT) is more effective than conventional physiotherapy to improve walking. Methods. A total of 41 patients with PD were randomly assigned to 45-minute treatment sessions (12 in all), 3 days a week, for 4 consecutive weeks of either robotic stepper training (RST; n = 21) using the Gait Trainer or physiotherapy (PT; n = 20) with active joint mobilization and a modest amount of conventional gait training. Participants were evaluated before, immediately after, and 1 month after treatment. Primary outcomes were 10-m walking speed and distance walked in 6 minutes. Results. Baseline measures revealed no statistical differences between groups, but the PT group walked 0.12 m/s slower; 5 patients withdrew. A statistically significant improvement was found in favor of the RST group (walking speed 1.22 ± 0.19 m/s [ P = .035]; distance 366.06 ± 78.54 m [ P < .001]) compared with the PT group (0.98 ± 0.32 m/s; 280.11 ± 106.61 m). The RAGT mean speed increased by 0.13 m/s, which is probably not clinically important. Improvements were maintained 1 month later. Conclusions. RAGT may improve aspects of walking ability in patients with PD. Future trials should compare robotic assistive training with treadmill or equal amounts of overground walking practice.
Combined Central and Peripheral Stimulation to Facilitate Motor Recovery After Stroke
Authors: Lindenberg Robert , Zhu Lin L. , Schlaug Gottfried
Published: January 2012

Background. Proof-of-principle studies have demonstrated transient beneficial effects of transcranial direct current stimulation (tDCS) on motor function in stroke patients, mostly after single treatment sessions. Objective. To assess the efficacy of multiple treatment sessions on motor outcome. Methods. The authors examined the effects of two 5-day intervention periods of bihemispheric tDCS and simultaneous occupational/physical therapy on motor function in a group of 10 chronic stroke patients. Results. The first 5-day period yielded an increase in Upper-Extremity Fugl-Meyer (UE-FM) scores by 5.9 ± 2.4 points (16.6% ± 10.6%). The second 5-day period resulted in further meaningful, although significantly lower, gains with an additional improvement of 2.3 ± 1.4 points in UE-FM compared with the end of the first 5-day period (5.5% ± 4.2%). The overall mean change after the 2 periods was 8.2 ± 2.2 points (22.9% ± 11.4%). Conclusion. The results confirm the efficacy of bihemispheric tDCS in combination with peripheral sensorimotor stimulation. Furthermore, they demonstrate that the effects of multiple treatment sessions in chronic stroke patients may not necessarily lead to a linear response function, which is of relevance for the design of experimental neurorehabilitation trials.
Thermal kinetics in explosive cladding of dissimilar metals
Authors: Saravanan S , Raghukandan K
Published: January 2012

Explosive cladding is a solid state process in which joining of dissimilar metals is accomplished by the acceleration of one of the components at extremely high velocity by employing chemical explosives. This study focuses on developing a model to predict the heat transfer during cladding and to determine the characteristics of the shock compressed gas developed at the standoff distance during cladding. The influence of interlayer on the amount of heat transferred is also investigated. It is concluded that the amount of heat transferred and the kinetic energy lost during collision at the interface determine the morphology of the interface.
Fatigue behaviour of magnesium to steel dissimilar friction stir lap joints
Authors: Jana S , Hovanski Y
Published: January 2012

A short study has been conducted to assess the performance of friction stir welded Mg/steel lap joints under dynamic loads. The major mode of failure was found to be top Mg sheet fracture. Crack initiation is noted to have taken place at the Mg/steel interface. The fatigue life of the joints is found to be significantly different than the fatigue data of the Mg alloy obtained from the literature. The reasons behind such a difference have been examined in this work.
Effect of MnO to hydrogen dissolution in CaF2–CaO–SiO2 based welding type fluxes
Authors: Park J-Y , Chang W-S , Sohn I
Published: January 2012

The effect of MnO on the hydrogen solubility in the CaF2–CaO–SiO2 based welding flux system at 1823 K has been studied. At an acidic slag composition of CaO/SiO2 molar ratio or basicity of 0·8 and below, MnO addition decreased the hydrogen solubility. At an intermediate slag composition of CaO/SiO2 molar ratios of 1·1 and 1·3, the hydrogen solubility as a function of MnO additions resulted in a parabolic behaviour showing a minimum and then increasing with higher MnO content. MnO was found to behave as a basic oxide, which decreases the hydrogen solubility when the incorporation hydroxyl mechanism is dominant for an acidic slag and increases the hydrogen solubility when the free hydroxyl mechanism is dominant for a basic slag. This change in the dominant hydrogen dissolution mechanism was also apparent from the hydrogen solubility results at various CaO/SiO2 molar ratios and fixed MnO contents. A higher hydrogen solubility in the slag is likely to lower the diffusible hydrogen content in the weld metal, and optimum MnO additions were suggested depending upon the basicity of the slag. Fourier transformed infrared analysis of as quenched slags showed that MnO depolymerised the slag network structure and correlated well with the effect on the hydrogen solubility in slags.
Weld appearance and microstructural characteristics of friction stir butt barrier welded joints of aluminium alloy to copper
Authors: Liu H J , Shen J J , Xie S , Huang Y X , Cui F , Liu C , Kuang L Y
Published: January 2012

Friction stir butt barrier welding, an improved method based on the friction stir butt welding process, in which a barrier was configured on the butt plate, was applied to the Cu–Al combination. The resultant Cu–Al joints presented good appearance when Al was adopted as the barrier. The pin shifting towards the Al side could improve the interior quality of the weld. However, the effect was limited when the pin offset increased to a certain value. As the tool rotation rate increased, the amount and size of the voids decreased first and then increased. There were two types of joint depending on the interfacial morphology: the smooth interface and the chaotic interface. When the pin offset was zero, the interface was occupied by large Cu fragments. As the pin offset increased, the joint interface transited first to the smooth type and then to the chaotic type. As the rotation rate increased, the laminate density around the interface decreased, and the sublayers in the laminates thinned.
Alternative current flux zoned tungsten inert gas welding process for aluminium alloys
Authors: Huang Y , Fan D , Shao F
Published: January 2012

A new variant of activating flux tungsten inert gas (TIG) welding process called flux zoned TIG (FZ-TIG) welding is proposed to weld aluminium alloys based on the mechanism of activating flux constricting welding arc. This process can not only increase weld penetration but also obtain perfect weld surface appearance simultaneously. An alternative current FZ-TIG welding is made using SiO2 as the side region material and flux FZ108 developed by the authors with uniform design method as the central region coat material. The weld penetration can reach above three times that of the conventional alternative current TIG welding. All the weld shape, weld microstructure and weld mechanical properties are fine. Except for argon shielding gas flowrate, other welding parameters, including welding current, welding speed, central coat width, central coat content and solvent, have great effect on the weld penetration of alternative current FZ-TIG welding for aluminium alloys.
Synchrotron diffraction analysis of retained austenite in welded transformation induced plasticity (TRIP) steels
Authors: Amirthalingam M , Hermans M J M , Huizenga R M , Offerman S E , Richardson I M , Gundlach C
Published: January 2012

A quantitative analysis of the retained austenite (RA) fractions in gas tungsten arc welded silicon and aluminium containing transformation induced plasticity steels was carried out by synchrotron X-ray diffraction measurements. The variation in RA transverse to the weld line was measured to study the effect of weld thermal cycles on the stabilisation of austenite in the heat affected zone (HAZ) and the fusion zone (FZ). The results showed that the FZ of silicon based steels contained a higher amount of RA (∼7%) than aluminium based steels, which contained only ∼4%. During the solidification of the weld pool, aluminium was found to partition to solidifying δ-ferrite and to stabilise the soft δ-ferrite grains at the fusion boundaries. Owing to this partitioning, the HAZ was enriched in carbon and the RA content was found to increase with distance from the fusion boundaries. In contrast, this partitioning behaviour was not present in silicon based transformation induced plasticity steels and a lesser amount of RA was found in the coarse grained HAZ than in the FZ.
Robust welding seam tracking using image seam extraction
Authors: Chen J S , Su G D , Xiang S B
Published: January 2012

Extracting single pixel wide paths is the core image processing problem in many vision based welding seam tracking applications. Traditional techniques such as edge detection and image thinning may not be effective for solving this problem on low quality welding images polluted by process noises. Based on the understanding of the prior knowledge about the welding images, we present in this paper a welding seam tracking method using the image seam extraction technique. Owing to its optimisation nature, the proposed method is robust to strong image noises caused by environmental factors such as uneven illumination, light interferences and welding spatters. In addition, the proposed method is of low time complexity and is highly adaptive to different types of welding images. Experimental results on a variety of welding images validate the effectiveness and efficiency of the proposed method.
Transplant tolerance is associated with reduced expression of cystathionine-γ-lyase that controls IL-12 production by dendritic cells and TH-1 immune responses
Authors: Vuillefroy de Silly Romain , Coulon Flora , Poirier Nicolas , Jovanovic Vojislav , Brouard Sophie , Ferchaud-Roucher Véronique , Blancho Gilles , Vanhove Bernard
Published: January 2012

Antigen-activated T lymphocytes undergo an immune or tolerogeneic response in part according to the activation status of their antigen-presenting cells. However, factors controlling the activation of antigen-presenting cells are not fully understood. In this study, we demonstrate that immune tolerance after organ allotransplantation in the rat is associated with a repressed intragraft expression of several enzymes of the trans-sulfuration pathway, including cystathionine γ-lyase (CSE). The pharmacologic blockade of CSE with propargylglycine delayed heart allograft rejection and abrogated type IV hypersensitivity but did not modify antibody responses, and was associated with a selective inhibition of the TH-1 type factors T-bet, IL-12, and IFN-γ. IL-12 repression could also be induced by propargylglycine in vitro in monocytes and dendritic cells (DCs), a phenomenon not mediated by changes to nuclear factor-κ B or hydrogen sulfide but that occurred together with a modulation of intracellular cysteine content. Intracellular cysteine levels were predominantly controlled in DCs by CSE activity, together with extracellular import via the Xc− transporter. Our results indicate that CSE plays a critical role in regulating IL-12 in monocytes and DCs and is down-modulated in transplant tolerance, presumably participating in the maintenance of the tolerant state.
Osteoblastic expansion induced by parathyroid hormone receptor signaling in murine osteocytes is not sufficient to increase hematopoietic stem cells
Authors: Calvi Laura M. , Bromberg Olga , Rhee Yumie , Weber Jonathan M. , Smith Julianne N. P. , Basil Miles J. , Frisch Benjamin J. , Bellido Teresita
Published: January 2012

Microenvironmental expansion of hematopoietic stem cells (HSCs) is induced by treatment with parathyroid hormone (PTH) or activation of the PTH receptor (PTH1R) in osteoblastic cells; however, the osteoblastic subset mediating this action of PTH is unknown. Osteocytes are terminally differentiated osteoblasts embedded in mineralized bone matrix but are connected with the BM. Activation of PTH1R in osteocytes increases osteoblastic number and bone mass. To establish whether osteocyte-mediated PTH1R signaling expands HSCs, we studied mice expressing a constitutively active PTH1R in osteocytes (TG mice). Osteoblasts, osteoclasts, and trabecular bone were increased in TG mice without changes in BM phenotypic HSCs or HSC function. TG mice had progressively increased trabecular bone but decreased HSC function. In severely affected TG mice, phenotypic HSCs were decreased in the BM but increased in the spleen. TG osteocytes had no increase in signals associated with microenvironmental HSC support, and the spindle-shaped osteoblastic cells that increased with PTH treatment were not present in TG bones. These findings demonstrate that activation of PTH1R signaling in osteocytes does not expand BM HSCs, which are instead decreased in TG mice. Therefore, osteocytes do not mediate the HSC expansion induced by PTH1R signaling. Further, osteoblastic expansion is not sufficient to increase HSCs.
Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome
Authors: Giona Fiorina , Teofili Luciana , Moleti Maria Luisa , Martini Maurizio , Palumbo Giovanna , Amendola Angela , Mazzucconi Maria Gabriella , Testi Anna Maria , Pignoloni Patrizia , Orlando Sonia Maria , Capodimonti Sara , Nanni Mauro , Leone Giuseppe , Larocca Luigi Maria , Foà Robin
Published: January 2012

Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2V617F mutations were present in 47.5% of ST and in no HT. The MPLS505A mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2V617F mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches.
Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes
Authors: Laidlaw Tanya M. , Kidder Molly S. , Bhattacharyya Neil , Xing Wei , Shen Shiliang , Milne Ginger L. , Castells Mariana C. , Chhay Heng , Boyce Joshua A.
Published: January 2012

Cysteinyl leukotriene (cysLT) overproduction is a hallmark of aspirin-exacerbated respiratory disease (AERD), but its mechanism is poorly understood. Because adherent platelets can convert the leukocyte-derived precursor leukotriene (LT)A4 to LTC4, the parent cysLT, through the terminal enzyme LTC4 synthase, we investigated the contribution of platelet-dependent transcellular cysLT production in AERD. Nasal polyps from subjects with AERD contained many extravascular platelets that colocalized with leukocytes, and the percentages of circulating neutrophils, eosinophils, and monocytes with adherent platelets were markedly higher in the blood of subjects with AERD than in aspirin-tolerant controls. Platelet-adherent subsets of leukocytes had higher expression of several adhesion markers than did platelet nonadherent subsets. Adherent platelets contributed more than half of the total LTC4 synthase activity of peripheral blood granulocytes, and they accounted for the higher level of LTC4 generation by activated granulocytes from subjects with AERD compared with aspirin-tolerant controls. Urinary LTE4 levels, a measure of systemic cysLT production, correlated strongly with percentages of circulating platelet-adherent granulocytes. Because platelet adherence to leukocytes allows for both firm adhesion to endothelial cells and augmented transcellular conversion of leukotrienes, a disturbance in platelet-leukocyte interactions may be partly responsible for the respiratory tissue inflammation and the overproduction of cysLTs that characterize AERD.
Unique features of primary myelofibrosis in Chinese
Authors: Xu Zefeng , Gale Robert Peter , Zhang Yue , Qin Tiejun , Chen Huishu , Zhang Peihong , Zhang Tianjiao , Liu Liu , Qu Shiqiang , Xiao Zhijian
Published: January 2012

Clinical and laboratory features of 642 consecutive Chinese subjects with primary myelofibrosis (PMF) were analyzed and compared with those of 1054 predominately white subjects with PMF. Chinese subjects were significantly younger, fewer had constitutional symptoms, and fewer had a palpable spleen or liver. Anemia, in contrast, was significantly more common in Chinese as was an increased white blood cell count and low platelet count. The reason for these differences is unclear, but it does not seem to be correlated with delayed diagnosis. A small but significantly increased proportion of Chinese had the JAK2V617F mutation but no difference in the frequency of haplotypes associated with PMF in whites. Survival of Chinese with PMF was also significantly longer than that of whites with PMF. We found commonly used staging systems for PMF such as the International Prognostic Scoring System and the Dynamic International Prognostic Scoring System were suboptimal predictors of survival in Chinese with PMF, and we developed a revised prognostic score that should help in comparison of data between studies of PMF in different populations and planning of clinical trials.
HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients
Authors: Kasang Christa , Ulmer Albrecht , Donhauser Norbert , Schmidt Barbara , Stich August , Klinker Hartwig , Kalluvya Samuel , Koutsilieri Eleni , Rethwilm Axel , Scheller Carsten
Published: January 2012

Background

HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.

Methods

In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.

Results

CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92],p= 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70];p= 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03];p= 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26];p= 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30];p= 0.0782). Viral load in both groups was similar (0.8 × 105ng/ml [0.2-42.4 × 105] vs. 1.1 × 105[0.5-12.2 × 105];p= 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.

Conclusions

Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.
Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis
Authors: Narvaez-Rivera Rodrigo M , Rendon Adrian , Salinas-Carmona Mario C , Rosas-Taraco Adrian G
Published: January 2012

Background

Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome.

Method

We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission.

Results

Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome.

Conclusion

The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.
Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells
Authors: Rhee Yun-Hee , Jeong Soo-Jin , Lee Hyo-Jeong , Lee Hyo-Jung , Koh Wonil , Jung Ji Hoon , Kim Sun-Hee , Sung-Hoon Kim
Published: January 2012

Background

Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells.

Results

Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control.

Conclusion

These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells.
Low-mutation-rate, reduced-genome Escherichia coli: an improved host for faithful maintenance of engineered genetic constructs
Authors: Csörgő Bálint , Fehér Tamás , Tímár Edit , Blattner Frederick R , Pósfai György
Published: January 2012

Background

Molecular mechanisms generating genetic variation provide the basis for evolution and long-term survival of a population in a changing environment. In stable, laboratory conditions, the variation-generating mechanisms are dispensable, as there is limited need for the cell to adapt to adverse conditions. In fact, newly emerging, evolved features might be undesirable when working on highly refined, precise molecular and synthetic biological tasks.

Results

By constructing low-mutation-rate variants, we reduced the evolutionary capacity of MDS42, a reduced-genomeE. colistrain engineered to lack most genes irrelevant for laboratory/industrial applications. Elimination of diversity-generating, error-prone DNA polymerase enzymes involved in induced mutagenesis achieved a significant stabilization of the genome. The resulting strain, while retaining normal growth, showed a significant decrease in overall mutation rates, most notably under various stress conditions. Moreover, the error-prone polymerase-free host allowed relatively stable maintenance of a toxic methyltransferase-expressing clone. In contrast, the parental strain produced mutant clones, unable to produce functional methyltransferase, which quickly overgrew the culture to a high ratio (50% of clones in a 24-h induction period lacked functional methyltransferase activity). The surprisingly large stability-difference observed between the strains was due to the combined effects of high stress-induced mutagenesis in the parental strain, growth inhibition by expression of the toxic protein, and selection/outgrowth of mutants no longer producing an active, toxic enzyme.

Conclusions

By eliminating stress-inducible error-prone DNA-polymerases, the genome of the mobile genetic element-freeE. colistrain MDS42 was further stabilized. The resulting strain represents an improved host in various synthetic and molecular biological applications, allowing more stable production of growth-inhibiting biomolecules.
Structure of reverse microemulsion-templated metal hexacyanoferrate nanoparticles
Authors: Gutiérrez-Becerra Alberto , Barcena-Soto Maximiliano , Soto Víctor , Arellano-Ceja Jesús , Casillas Norberto , Prévost Sylvain , Noirez Laurence , Gradzielski Michael , Escalante José I
Published: January 2012

The droplet phase of a reverse microemulsion formed by the surfactant cetyltrimethylammonium ferrocyanide was used as a matrix to synthesize nanoparticles of nickel hexacyanoferrate by adding just a solution of NiCl2 to the microemulsion media. Dynamic light scattering and small-angle neutron scattering measurements show that the reverse microemulsion droplets employed have a globular structure, with sizes that depend on water content. Transmission electron microscopy and electron diffraction are used to obtain information about the structure of the synthesized nanoparticles. The results show that the size and shape of the coordination compound nanoparticles correspond with the size and shape of the droplets, suggesting that the presented system constitutes an alternative method of the synthesis of metal hexacyanoferrate nanoparticles.
Phylogenetic analysis of Chinese sheeppox and goatpox virus isolates
Authors: Zhou Tao , Jia Huaijie , Chen Guohua , He Xiaobing , Fang Yongxiang , Wang Xiaoxia , Guan Qisai , Zeng Shuang , Cui Qing , Jing Zhizhong
Published: January 2012

Background

Sheeppox virus (SPPV) and goatpox virus (GTPV), members of theCapripoxvirusgenus of thePoxviridaefamily are causative agents of sheep pox and goat pox respectively, which are important contagious diseases and endemic in central and northern Africa, the Middle and Far East, and the Indian sub-continent. Both sheep pox and goat pox can cause wool and hide damage, and reduce the production of mutton and milk, which may result in significant economic losses and threaten the stockbreeding. In this study, three SPPVs and two GTPVs were collected from China in 2009 and 2011. We described the sequence features and phylogenetic analysis of the P32 gene, GPCR gene and RPO30 gene of the SPPVs and GTPVs to reveal their genetic relatedness.

Results

Sequence and phylogenetic analysis showed that there was a close relationship among SPPV/GanS/2/2011/China, SPPV/GanS/1/2011/China and SPPV/NingX/2009/China. They were clustered on the same SPPV clade. GTPV/HuB/2009/China and GS-V1 belonged to the GTPV lineage. GS-V1 was closely related to other GTPV vaccine strains. GTPV/HuB/2009/China and GS-V1 were clustered with GTPVs from China and some southern Asian countries.

Conclusion

This study may expand the datum for spread trend research of Chinese SPPVs and GTPVs, meanwhile provide theoretical references to improve the preventive and control strategy.
A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells
Authors: Chen Eric Y , Garnica Maria , Wang Yung-Chen , Mintz Alexander J , Chen Chi-Shuo , Chin Wei-Chun
Published: January 2012

Background

Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca2+ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain.

Results

TiO2 NP exposure increased both histamine secretion and cytosolic Ca2+ concentration ([Ca2+]C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca2+ levels resulted primarily from an extracellular Ca2+ influx via membrane L-type Ca2+ channels. Unspecific Ca2+ entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca2+ signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca2+]C and histamine secretion.

Conclusion

Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.
Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions
Authors: Alvarez-Bolado Gonzalo , Paul Fabian A , Blaess Sandra
Published: January 2012

Background

The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh- expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary.

Results

Shh- expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh- expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes.

Conclusions

We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh- expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains and that there is little or no cell mixing between the tuberal and anterior or the preoptic and anterior hypothalamus. Finally, we show that, in the tuberal hypothalamus, neurons destined for every mediolateral level are produced during a period of days, in conflict with the current 'three-wave' model of hypothalamic neurogenesis. Our work sets the stage for a deeper developmental analysis of this complex and important brain region.