bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered neutrophil maturation patterns that limit identification of myelodysplastic syndromes
Authors: Monaghan Sara A. , Surti Urvashi , Doty Ketah , Craig Fiona E.
Published: March 2012

Background:

Altered neutrophil maturation patterns have been reported useful for identification of myelodysplastic syndromes (MDS).

Methods:

Neutrophil maturation patterns based on CD11b, CD13, and CD16 were visually and numerically evaluated in 19 control, 23 MDS, 37 nondiagnostic for MDS (NDM) specimens, and 19 also processed 1 and 2 days subsequently.

Results:

In contrast to maturation patterns illustrated previously by others as “normal,” 84% of controls displayed diminished acquisition of CD16, imparting a contracted appearance. Such divergence from published “normal” patterns was usually mild‐moderate, considered nonspecific, and associated with delayed processing: longer intervals between collection and processing (median 20.5 vs. 5.2 h), and following 1 and 2 days delay. Findings restricted to nonspecific contraction were found in 56% MDS and 78% NDM specimens. Evaluation for aberrant patterns was still performed with mild‐moderate contraction present, but concern for over interpretation led to use of an equivocal‐aberrant category. Nine cases had aberrant or equivocal‐aberrant patterns (seven MDS, two NDM) with distinct visual alterations that differed from nonspecific contraction and had numerical evidence for a left shift: myeloblasts increased (67%) and least mature neutrophils (CD11b‐/low, CD16‐/low) increased (78%). Although evidence for a left shift was associated with MDS, it was also seen in NDM specimens with a synchronous left shift.

Conclusions:

Neutrophil maturation patterns that diverge from previously illustrated “normal” patterns, not specific for MDS, may be common in some settings. Laboratories seeking to implement FC evaluation for MDS must determine which findings have sufficient specificity for MDS within their own practice and patient population. © 2012 International Clinical Cytometry Society
Psychosocial risk factors of loss of control eating in primary school children: A retrospective case‐control study
Authors: Hartmann Andrea Sabrina , Czaja Julia , Rief Winfried , Hilbert Anja
Published: March 2012

Objective:

To provide a comprehensive investigation of the retrospective correlates of loss of control (LOC) over eating in children close to the onset of their first LOC eating episodes.

Method:

A community‐based, case‐control design was used to compare matched groups of 60 children with and without LOC eating. Retrospective correlates were assessed using a child‐adapted version of the Oxford Risk Factor Interview.

Results:

Children with LOC eating revealed greater levels of exposure to parental problems, (e.g., underinvolvement, arguments, and depression of family members) and dieting‐related risk factors than children without LOC eating. Predictors of LOC eating were risk correlates parental underinvolvement, and critical comments by the family and the critical life event change of school.

Discussion:

Results underline the influence of parental behavior and the impact of dieting behavior on the development of non‐normative eating in middle childhood. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012; 45:751–758)
Efficient and General Protocol for Sonogashira Cross‐Coupling Reactions of Maleimides
Authors: Souffrin Agathe , Croix Cécile , Viaud‐Massuard Marie‐Claude
Published: March 2012

Maleimides are involved for the first time in Sonogashira cross‐coupling reactions. Sonogashira conditions have been developed to allow subsequent coupling of various terminal alkynes at room temperature in moderate to excellent yields. These results open the way to innovative synthesis strategies for various difunctionalized maleimide derivatives.
Total Syntheses of D‐xylo‐ and D‐arabino‐Phytosphingosine Based on the Syntheses of Chiral 1,3‐Oxazines
Authors: Mu Yu , Jin Tian , Kim Gun‐Woo , Kim Jin‐Seok , Kim Sung‐Soo , Tian Yong‐Shou , Oh Chang‐Young , Ham Won‐Hun
Published: March 2012

An efficient, stereocontrolled, and short synthetic method for the preparation D‐xylo‐ and D‐arabino‐phytosphingsine was achieved utilizing chiral oxazines. The key features of this strategy are the stereoselective intramolecular oxazine formation catalyzed by palladium(0) and an intermolecular olefin cross‐metathesis reaction.
Quantitative impurity analysis of monoclonal antibody size heterogeneity by CE‐LIF: Example of development and validation through a quality‐by‐design framework
Authors: Michels David A. , Parker Monica , Salas‐Solano Oscar
Published: March 2012

This paper describes the framework of quality by design applied to the development, optimization and validation of a sensitive capillary electrophoresis‐sodium dodecyl sulfate (CE‐SDS) assay for monitoring impurities that potentially impact drug efficacy or patient safety produced in the manufacture of therapeutic MAb products. Drug substance or drug product samples are derivatized with fluorogenic 3‐(2‐furoyl)quinoline‐2‐carboxaldehyde and nucleophilic cyanide before separation by CE‐SDS coupled to LIF detection. Three design‐of‐experiments enabled critical labeling parameters to meet method requirements for detecting minor impurities while building precision and robustness into the assay during development. The screening design predicted optimal conditions to control labeling artifacts while two full factorial designs demonstrated method robustness through control of temperature and cyanide parameters within the normal operating range. Subsequent validation according to the guidelines of the International Committee of Harmonization showed the CE‐SDS/LIF assay was specific, accurate, and precise (RSD ≤ 0.8%) for relative peak distribution and linear (R > 0.997) between the range of 0.5–1.5 mg/mL with LOD and LOQ of 10 ng/mL and 35 ng/mL, respectively. Validation confirmed the system suitability criteria used as a level of control to ensure reliable method performance.
Kir4.1 channels mediate a depolarization of hippocampal astrocytes under hyperammonemic conditions in situ
Authors: Stephan Jonathan , Haack Nicole , Kafitz Karl W. , Durry Simone , Koch Daniel , Hochstrate Peter , Seifert Gerald , Steinhäuser Christian , Rose Christine R.
Published: March 2012

Increased ammonium (NH4
+) concentration in the brain is the prime candidate responsible for hepatic encephalopathy (HE), a serious neurological disorder caused by liver failure and characterized by disturbed glutamatergic neurotransmission and impaired glial function. We investigated the mechanisms of NH4
+‐induced depolarization of astrocytes in mouse hippocampal slices using whole‐cell patch‐clamp and potassium‐selective microelectrodes. At postnatal days (P) 18–21, perfusion with 5 mM NH4
+ evoked a transient increase in the extracellular potassium concentration ([K+]o) by about 1 mM. Astrocytes depolarized by on average 8 mV and then slowly repolarized to a plateau depolarization of 6 mV, which was maintained during NH4
+ perfusion. In voltage‐clamped astrocytes, NH4
+ induced an inward current and a reduction in membrane resistance. Amplitudes of [K+]o transients and astrocyte depolarization/inward currents increased from P3–4 to P18–21. Perfusion with 100 μM Ba2+ did not alter [K+]o transients but strongly reduced both astrocyte depolarization and inward currents. NH4
+‐induced depolarization and inward currents were also virtually absent in slices from Kir4.1 −/− mice, while [K+]o transients were unaltered. Blocking Na+/K+‐ATPase with ouabain caused an immediate and complex increase in [K+]o. Taken together, our results are in agreement with the hypothesis that reduced uptake of K+ by the Na+, K+‐ATPase in the presence of NH4
+ disturbs the extracellular K+ homeostasis. Furthermore, astrocytes depolarize in response to the increase in [K+]o and by influx of NH4
+ through Kir4.1 channels. The depolarization reduces the astrocytes' capacity for channel‐mediated flux of K+ and for uptake of glutamate and might hereby contribute to the pathology of HE. © 2012 Wiley Periodicals, Inc.
Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy
Authors: Yang Tianhua , Luo Cheng , Li Qifu , Guo Zhiwei , Liu Ling , Gong Qiyong , Yao Dezhong , Zhou Dong
Published: March 2012

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Representation and propagation of epileptic activity in absences and generalized photoparoxysmal responses
Authors: Moeller Friederike , Muthuraman Muthuraman , Stephani Ulrich , Deuschl Günther , Raethjen Jan , Siniatchkin Michael
Published: March 2012

Although functional imaging studies described networks associated with generalized epileptic activity, propagation patterns within these networks are not clear. In this study, electroencephalogram (EEG)‐based coherent source imaging dynamic imaging of coherent sources (DICS) was applied to different types of generalized epileptiform discharges, namely absence seizures (10 patients) and photoparoxysmal responses (PPR) (eight patients) to describe the representation and propagation of these discharges in the brain. The results of electrical source imaging were compared to EEG‐functional magnetic resonance imaging (fMRI) which had been obtained from the same data sets of simultaneous EEG and fMRI recordings. Similar networks were described by DICS and fMRI: (1) absence seizures were associated with thalamic involvement in all patients. Concordant results were also found for brain areas of the default mode network and the occipital cortex. (2) Both DICS and fMRI identified the occipital, parietal, and the frontal cortex in a network associated with PPR. (3) However, only when PPR preceded a generalized tonic‐clonic seizure, the thalamus was involved in the generation of PPR as shown by both imaging techniques. Partial directed coherence suggested that during absences, the thalamus acts as a pacemaker while PPR could be explained by a cortical propagation from the occipital cortex via the parietal cortex to the frontal cortex. In conclusion, the electrical source imaging is not only able to describe similar neuronal networks as revealed by fMRI, including deep sources of neuronal activity such as the thalamus, but also demonstrates interactions interactions within these networks and sheds light on pathogenetic mechanisms of absence seizures and PPR. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Dynamic brain structural changes after left hemisphere subcortical stroke
Authors: Fan Fengmei , Zhu Chaozhe , Chen Hai , Qin Wen , Ji Xunming , Wang Liang , Zhang Yujin , Zhu Litao , Yu Chunshui
Published: March 2012

This study aimed to quantify dynamic structural changes in the brain after subcortical stroke and identify brain areas that contribute to motor recovery of affected limbs. High‐resolution structural MRI and neurological examinations were conducted at five consecutive time points during the year following stroke in 10 patients with left hemisphere subcortical infarctions involving motor pathways. Gray matter volume (GMV) was calculated using an optimized voxel‐based morphometry technique, and dynamic changes in GMV were evaluated using a mixed‐effects model. After stroke, GMV was decreased bilaterally in brain areas that directly or indirectly connected with lesions, which suggests the presence of regional damage in these “healthy” brain tissues in stroke patients. Moreover, the GMVs of these brain areas were not correlated with the Motricity Index (MI) scores when controlling for time intervals after stroke, which indicates that these structural changes may reflect an independent process (such as axonal degeneration) but cannot affect the improvement of motor function. In contrast, the GMV was increased in several brain areas associated with motor and cognitive functions after stroke. When controlling for time intervals after stroke, only the GMVs in the cognitive‐related brain areas (hippocampus and precuneus) were positively correlated with MI scores, which suggests that the structural reorganization in cognitive‐related brain areas may facilitate the recovery of motor function. However, considering the small sample size of this study, further studies are needed to clarify the exact relationships between structural changes and recovery of motor function in stroke patients. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
The benefits of peer leader programs: An overview from the literature
Authors: Shook Jaime L. , Keup Jennifer R.
Published: March 2012

This chapter provides a review of the literature on peer leadership with specific emphasis on the benefits of these programs to the students being served, to those who engage as peer leaders, and to the institution.
Integrating technology into peer leader responsibilities
Authors: Johnson Melissa L.
Published: March 2012

This chapter focuses on the emerging role of technology as part of peer leader positions on college campuses and describes how peer leaders can apply technological skills to their formal and informal job responsibilities.
Adult‐born hippocampal neurons promote cognitive flexibility in mice
Authors: Burghardt Nesha S. , Park Eun Hye , Hen René , Fenton André A.
Published: March 2012

The hippocampus is involved in segregating memories, an ability that utilizes the neural process of pattern separation and allows for cognitive flexibility. We evaluated a proposed role for adult hippocampal neurogenesis in cognitive flexibility using variants of the active place avoidance task and two independent methods of ablating adult‐born neurons, focal X‐irradiation of the hippocampus, and genetic ablation of glial fibrillary acidic protein positive neural progenitor cells, in mice. We found that ablation of adult neurogenesis did not impair the ability to learn the initial location of a shock zone. However, when conflict was introduced by switching the location of the shock zone to the opposite side of the room, irradiated and transgenic mice entered the new shock zone location significantly more than their respective controls. This impairment was associated with increased upregulation of the immediate early gene Arc in the dorsal dentate gyrus, suggesting a role for adult neurogenesis in modulating network excitability and/or synaptic plasticity. Additional experiments revealed that irradiated mice were also impaired in learning to avoid a rotating shock zone when it was added to an initially learned stationary shock zone, but were unimpaired in learning the identical simultaneous task variant if it was their initial experience with place avoidance. Impaired avoidance could not be attributed to a deficit in extinction or an inability to learn a new shock zone location in a different environment. Together these results demonstrate that adult neurogenesis contributes to cognitive flexibility when it requires changing a learned response to a stimulus‐evoked memory. © 2012 Wiley Periodicals, Inc.
Synaptic underpinnings of altered hippocampal function in glutaminase‐deficient mice during maturation
Authors: Gaisler‐Salomon Inna , Wang Yvonne , Chuhma Nao , Zhang Hong , Golumbic Yaela N. , Mihali Andra , Arancio Ottavio , Sibille Etienne , Rayport Stephen
Published: March 2012

Glutaminase‐deficient mice (GLS1 hets), with reduced glutamate recycling, have a focal reduction in hippocampal activity, mainly in CA1, and manifest behavioral and neurochemical phenotypes suggestive of schizophrenia resilience. To address the basis for the hippocampal hypoactivity, we examined synaptic plastic mechanisms and glutamate receptor expression. Although baseline synaptic strength was unaffected in Schaffer collateral inputs to CA1, we found that long‐term potentiation was attenuated. In wild‐type (WT) mice, GLS1 gene expression was highest in the hippocampus and cortex, where it was reduced by about 50% in GLS1 hets. In other brain regions with lower WT GLS1 gene expression, there were no genotypic reductions. In adult GLS1 hets, NMDA receptor NR1 subunit gene expression was reduced, but not AMPA receptor GluR1 subunit gene expression. In contrast, juvenile GLS1 hets showed no reductions in NR1 gene expression. In concert with this, adult GLS1 hets showed a deficit in hippocampal‐dependent contextual fear conditioning, whereas juvenile GLS1 hets did not. These alterations in glutamatergic synaptic function may partly explain the hippocampal hypoactivity seen in the GLS1 hets. The maturity‐onset reduction in NR1 gene expression and in contextual learning supports the premise that glutaminase inhibition in adulthood should prove therapeutic in schizophrenia. © 2012 Wiley Periodicals, Inc.
Role of transformational leadership in effective organizational knowledge creation practices: Mediating effects of employees' work engagement
Authors: Hoon Song Ji , Kolb Judith A. , Hee Lee Ung , Kyoung Kim Hye
Published: March 2012

Engagement as an area of increasing interest has been discussed in terms of a wide array of organizational policies, practices, and outcomes. This study focuses on a specific aspect of work engagement and its relationship with leadership practices and the outcome of knowledge creation. The mediating effect of employees' work engagement level was assessed to explain the relationship between transformational leadership and organizational knowledge creation practices in the Korean business context. A total of 432 cases were collected from Korean for‐profit organizations. Hierarchical multiple regression analysis and structural equation modeling were used along with basic descriptive analysis and interconstruct correlation analysis to examine the structural relationships and the mediating effect among the constructs. Results found transformational leadership to be a statistically significant construct that has an impact on employees' work engagement and organizational knowledge creation practices. Additionally, employees' work engagement was found to be a statistically significant mediator that explains the relationship between transformational leadership and organizational knowledge creation practices.
Evolution of approaches in conducting total diet studies
Authors: Betsy A. , Sudershan Rao V. , Polasa K.
Published: March 2012

One of the main routes of human exposure to contaminants is through food. To assess the health impact, it is necessary to determine the levels of contaminants in foods and evaluate the exposure estimates. Many countries regularly conduct total diet studies as a method of assessing the exposure of the population to various contaminants present in foods. It is a comprehensive approach and is based on determination of contaminants in foods. The risk assessment is done by taking into account the actual quantity consumed by specific age–sex groups of a population. The approach has developed through multiple changes since its inception. This article aims to review and summarize the changes that have occurred in different countries. Some of the attempts include the addition of analytes and the use of sophisticated instrumentation in conjunction with better extraction and types of food commodities. The present analytical methods have reduced the limits of detection for many analytes in many food matrices, making this approach much more accurate and sensitive. Copyright © 2012 John Wiley & Sons, Ltd.
Gene expression profiling reveals potential key pathways involved in pyrazinamide‐mediated hepatotoxicity in Wistar rats
Authors: Zhang Yun , Jiang Zhenzhou , Su Yijing , Chen Mi , Li Fu , Liu Li , Sun Lixin , Wang Yun , Zhang Shuang , Zhang Luyong
Published: March 2012

Pyrazinamide (PZA) is an important sterilizing prodrug that shortens the duration of tuberculosis therapy. However, hepatotoxicity has been reported during clinical trials investigating PZA. To determine the hepatotoxic effects of PZA in vivo and to further investigate the underlying cellular mechanism, we profiled the gene expression patterns of PZA‐treated rat livers by microarray analysis. Wistar rats of both sexes were orally administered PZA at doses of 0.5, 1.0 and 2.0 g kg−1 for 28 days. Body weight, absolute and relative liver weight, biochemical analysis, histopathology, oxidative stress parameters in liver homogenates and changes in global transcriptomic expression were evaluated to study the hepatotoxic effects of PZA. Our results confirm the dose‐dependent and sex‐related hepatotoxicity of PZA. Female rats were more sensitive to PZA‐induced hepatotoxicity than males. Furthermore, changes in the activity of major antioxidant enzymes and nonenzymatic antioxidants (superoxide dismutase, total antioxidant capacity, glutathione and malondialdehyde), indicating the development of oxidative stress, were more significant in the PZA‐treated group. PZA‐induced gene expression changes were related to pathways involved in drug metabolism, peroxisome proliferator‐activated receptor (PPAR) signaling, oxidative stress and apoptosis. Real‐time polymerase chain reaction confirmed the regulation of selected genes involved in PZA‐hepatotoxicity (Ephx1, Cyp2b1, Gstm1, Gstp1, Fabp7, Acaa1, Cpt‐1b, Cyp8b1, Hmox1 and Ntrk1). We observed for the first time that these genes have effects on PZA‐induced hepatotoxicity. In addition, drug metabolism and PPAR signaling pathways may play an important role in PZA hepatotoxicity. Taken together, these findings will be useful for future PZA hepatotoxicity studies. Copyright © 2012 John Wiley & Sons, Ltd.
Runx1 dose-dependently regulates endochondral ossification during skeletal development and fracture healing
Authors: Soung Do Y , Talebian Laleh , Matheny Christina J , Guzzo Rosa , Speck Maren E , Lieberman Jay R , Speck Nancy A , Drissi Hicham
Published: March 2012

Runx1 is expressed in skeletal elements, but its role in fracture repair has not been analyzed. We created mice with a hypomorphic Runx1 allele (Runx1L148A) and generated Runx1L148A/− mice in which >50% of Runx1 activity was abrogated. Runx1L148A/− mice were viable but runted. Their growth plates had extended proliferating and hypertrophic zones, and the percentages of Sox9-, Runx2-, and Runx3-positive cells were decreased. Femoral fracture experiments revealed delayed cartilaginous callus formation, and the expression of chondrogenic markers was decreased. Conditional ablation of Runx1 in the mesenchymal progenitor cells of the limb with Prx1-Cre conferred no obvious limb phenotype; however, cartilaginous callus formation was delayed following fracture. Embryonic limb bud–derived mesenchymal cells showed delayed chondrogenesis when the Runx1 allele was deleted ex vivo with adenoviral-expressed Cre. Collectively, our data suggest that Runx1 is required for commitment and differentiation of chondroprogenitor cells into the chondrogenic lineage. © 2012 American Society for Bone and Mineral Research.
Time to onset of antifracture efficacy and year-by-year persistence of effect of zoledronic acid in women with osteoporosis
Authors: Boonen Steven , Eastell Richard , Su Guoqin , Mesenbrink Peter , Cosman Felicia , Cauley Jane A , Reid Ian R , Claessens Frank , Vanderschueren Dirk , Lyles Kenneth W , Black Dennis M
Published: March 2012

Oral bisphosphonates reduce fracture risk in osteoporotic patients but are often associated with poor compliance, which may impair their antifracture effects. This post hoc analysis assessed the time to onset and persistence of the antifracture effect of zoledronic acid, a once-yearly bisphosphonate infusion, in women with osteoporosis. Data from 9355 women who were randomized in two placebo-controlled pivotal trials were included. Endpoints included reduction in the rate of any clinical fracture at 6, 12, 18, 24, and 36 months in the zoledronic acid group compared with placebo, and the year-by-year incidence of all clinical fractures over 3 years. Cox proportional hazards regression was used to determine the timing of onset of antifracture efficacy. A generalized estimating equation model was used to assess fracture reduction for the 3 consecutive years of treatment, thereby evaluating persistence of effect. Safety results from women in the two studies were collated. Zoledronic acid reduced the risk of all clinical fractures at 12 months (hazard ratio [HR] = 0.75, 95% confidence interval [CI] 0.61–0.92, p = 0.0050) with significant reductions maintained at all subsequent time points. Year-by-year analysis showed that zoledronic acid reduced the risk for all clinical fractures compared with the placebo group in each of the 3 years (year 1: odds ratio [OR] = 0.74, 95% CI 0.60–0.91, p = 0.0044; year 2: OR = 0.53, 95% CI 0.42–0.66, p < 0.0001; year 3: OR = 0.61, 95% CI 0.48–0.77, p < 0.0001). This antifracture effect was persistent over 3 years, with the reductions in years 2 and 3 slightly larger than in year 1 (p = 0.097). This analysis shows that zoledronic acid offered significant protection from clinical fractures as early as 12 months. When administered annually, its beneficial effects persisted for at least 3 years. © 2012 American Society for Bone and Mineral Research.
Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX
Authors: McCloskey Eugene V , Johansson Helena , Oden Anders , Austin Matt , Siris Ethel , Wang Andrea , Lewiecki E Michael , Lorenc Roman , Libanati Cesar , Kanis John A
Published: March 2012

Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX. © 2012 American Society for Bone and Mineral Research.
Partitions of V(n, q) into 2‐ and s‐Dimensional Subspaces
Authors: Seelinger G. , Sissokho P. , Spence L. , Eynden C. Vanden
Published: March 2012

Let denote a vector space of dimension n over the field with q elements. A set of subspaces of V is a (vector space) partition of V if every nonzero element of V is contained in exactly one subspace in . Suppose that is a partition of V with subspaces of dimension for . Then we call the type of the partition . Which possible types correspond to actual partitions is in general an open question. We prove that for any odd integer and for any integer , the existence of partitions of across a suitable range of types guarantees the existence of partitions of of essentially all the types for any integer . We then apply this result to construct new classes of partitions of V. © 2012 Wiley Periodicals, Inc. J. Combin. Designs 20: 467‐482, 2012
Simple Signed Steiner Triple Systems
Authors: Ghorbani E. , Khosrovshahi G. B.
Published: March 2012

LetXbe av‐set,be a set of 3‐subsets (triples) ofX, andbe a partition ofwith. The pairis called a simple signed Steiner triple system, denoted by ST, if the number of occurrences of every 2‐subset ofXin triplesis one more than the number of occurrences in triples. In this paper, we prove thatexists if and only if,, and, whereand for,. © 2012 Wiley Periodicals, Inc. J. Combin. Designs 20: 332–343, 2012
Four Mutually Orthogonal Latin Squares of Order 14
Authors: Todorov D. T.
Published: March 2012

The paper gives example of orthogonal array OA(6, 14) obtained from a difference matrix . The construction is equivalent to four mutually orthogonal Latin squares (MOLS) of order 14. © 2012 Wiley Periodicals, Inc. J. Combin. Designs 20: 363–367, 2012
Liquid velocity in a high‐solids‐loading three‐phase external‐loop airlift reactor
Authors: Milivojevic Milan , Pavlou Stavros , Bugarski Branko
Published: March 2012

BACKGROUND: Airlift reactors are of interest for many different processes, especially for three‐phase systems. In this study the behavior of a high‐loading three‐phase external‐loop airlift reactor was examined. In particular, the effect of parameters such as airflow rate (riser superficial gas velocities between 0.003 and 0.017 m s−1), solids loading (up to 50%, v/v) on liquid circulation velocity in the air‐water‐alginate beads system as a crucial hydrodynamic parameter was studied.

RESULTS: It was observed that increase of the airflow rate resulted in increase of the liquid velocity in the system. The same result but less pronounced was observed by introducing small amounts of solid particles up to 7.5% v/v. However, further introduction of solids caused decrease of the liquid velocity. Laminar regime for the liquid circulation was observed for low gas velocities. Minimum gas velocities for recirculation initiation in the reactor were determined for all solid loadings and linear dependence on the solid content was found. Gas holdups for the three‐phase system were larger than for the two‐phase system in all experiments. A simple model for predicting the liquid circulation velocity in the three‐phase system with high solid loading of low‐density particles was developed. This model is based on the viscosity of integrated medium (solid + liquid) which is a new aspect to analyze this phenomenon.

CONCLUSIONS: The developed model shows very good agreement with the experimental results for all solid loadings. It also includes the influence of reactor geometry on the liquid circulation velocity thus enabling optimization. Copyright © 2012 Society of Chemical Industry
Anaerobic co‐digestion of food waste leachate and piggery wastewater for methane production: statistical optimization of key process parameters
Authors: Han Man Jae , Behera Shishir Kumar , Park Hung‐Suck
Published: March 2012

BACKGROUND: Anaerobic co‐digestion of refractory liquid organic wastes is an alternative environmental management strategy with economic benefits arising out of biogas production. Laboratory‐scale experimental investigations were carried out on the anaerobic co‐digestion of two liquid organic wastes, food waste leachate (FWL) and piggery wastewater (PWW). Three important parameters affecting methane yield were chosen for this study, namely, mixing ratio, alkalinity and salinity, which were optimized using response surface methodology.

RESULTS: The results were analyzed statistically and the optimum conditions identified as: mixing ratio (FWL: PWW) 33 (in terms of volatile solid, w/w) (2 on v/v), alkalinity 2850 mg CaCO3 L−1, and salinity 3.4 g NaCl L−1. Under the optimum conditions, a cumulative methane yield (CMY) of 310 mL CH4 g−1 VSadded and VS reduction (VSR) of 54% were predicted. Mixing ratio and alkalinity showed the greatest individual and interactive effects on CMY and VSR (P < 0.05). A confirmation experiment under optimum conditions showed a CMY and VSR of 323 mL CH4 g−1 VSadded and 50%, respectively. This was only 1.04% and 1.1%, respectively, different from the predicted values.

CONCLUSION: Anaerobic co‐digestion of FWL and PWW carried out under the optimum condition may be a feasible and efficient treatment option for methane production. Copyright © 2012 Society of Chemical Industry
On Cyclic Decompositions of Complete Graphs into Tripartite Graphs
Authors: Bunge Ryan C. , Chantasartrassmee Avapa , El-Zanati Saad I. , Eynden Charles Vanden
Published: March 2012

We introduce two new labelings for tripartite graphs and show that if a graph G with n edges admits either of these labelings, then there exists a cyclic G‐decomposition of for every positive integer x. We also show that if G is the union of two vertext‐disjoint cycles of odd length, other than , then G admits one of these labelings.
Pebbling Graphs of Diameter Three and Four
Authors: Postle Luke , Streib Noah , Yerger Carl
Published: March 2012

Given a configuration of pebbles on the vertices of a connected graph G, a pebbling move is defined as the removal of two pebbles from some vertex and the placement of one of these on an adjacent vertex. The pebbling number of a graph G is the smallest integer k such that for each vertex v and each configuration of k pebbles on G there is a sequence of pebbling moves that places at least one pebble on v. We improve on a bound of Bukh by showing that the pebbling number of a graph of diameter three on n vertices is at most , and this bound is best possible. Further, we obtain an asymptotic bound of for the pebbling number of graphs of diameter four. Finally, we prove an asymptotic bound for pebbling graphs of arbitrary diameter, namely that the pebbling number for a diameter d graph on n vertices is at most , where is a constant depending upon d. This also improves another bound of Bukh.
A Class of Three‐Colorable Triangle‐Free Graphs
Authors: Radovanović Marko , Vušković Kristina
Published: March 2012

The chromatic number of a triangle‐free graph can be arbitrarily large. In this article, we show that if all subdivisions of K2, 3 are also excluded as induced subgraphs, then the chromatic number becomes bounded by 3. We give a structural characterization of this class of graphs, from which we derive an coloring algorithm, where n denotes the number of vertices and m the number of edges of the input graph.
PARP‐1 deletion promotes subventricular zone neural stem cells toward a glial fate
Authors: Plane Jennifer M. , Grossenbacher Steven K. , Deng Wenbin
Published: March 2012

Identification of critical factors involved in oligodendroglial fate specification from endogenous neural stem cells is relevant to the development of therapeutic interventions that aim to promote remyelination. Here we report a novel role of the DNA repair protein poly‐ADP‐ribose polymerase‐1 (PARP‐1) in regulating the neural stem cell profile in the postnatal mouse forebrain subventricular zone (SVZ). We observed increased expression of Sox2 and Sox10 in the SVZ of postnatal day 11 (P11) PARP‐1 knockout mice. This increase corresponded to increased Olig2 expression in Sox2‐positive cells of the PARP‐1 knockout mouse SVZ and decreased Map2abc expression compared with Sox2/Olig2 and Sox2/Map2abc expression in wild‐type mice. We noted enhanced expression of proliferating oligodendrocyte progenitor cells (OPCs) at the expense of proliferating neuroblasts in the SVZ of PARP‐1 knockout mice, by using Olig1/Ki67/DCX, NG2/Ki67/DCX, and PDGFR/BrdU/TuJ1 immunofluorescence labeling. In addition, the percentage of BrdU/Olig2 double‐labeled cells increased in the SVZ and corpus callosum of PARP‐1 knockout mice compared with wild‐type mice. We also observed a decrease in DCX‐positive cells without a decrease in the overall SVZ area in PARP‐1 knockout mice, further indicating a switch from neuroblast to OPC fate. PARP‐1 knockout mice displayed thinning of MBP expression in the corpus callosum and external capsule, suggesting that the enhanced OPC proliferation in the SVZ might compensate for deficiency in myelination. Together, our results show that PARP‐1 deletion promotes SVZ neural stem cells toward a glial fate and suggest that future studies target PARP‐1 as a potential therapeutic strategy for demyelinating diseases. © 2012 Wiley Periodicals, Inc.
Extreme monthly precipitation pattern in China and its dependence on Southern Oscillation
Authors: Wan Shiquan , Hu Yuling , You Zhiyuan , Kang Jianpeng , Zhu Jianguo
Published: March 2012

Using the generalized Pareto distribution (GPD) and a spatial scheme of parameter estimation, spatial patterns of extreme monthly precipitation (EMP) in China were studied using 740 stations' data from 1960 to 2007. The spatial patterns of EMP are described by the GPD's scale and shape parameters, whose regional features depend on ENSO activities. The results show that the scale parameter (representing variability) in monsoon areas, such as southern China, is greater than that of non‐monsoon areas, such as northern China, and that it is greater in summer than that in autumn. The shape parameter (representing record‐breaking probability) reaches a maximum in non‐monsoon areas and a minimum in monsoon areas. For the time scale, record‐breaking events would occur more easily in the seasons other than summer. The regional difference in terms of dependence of EMP's variability on Southern Oscillation (SO) was also related to the monsoon transition zone. The variability with great dependence on SO was in the Qinghai–Tibet Plateau and in the region between the Yangtze and Yellow rivers, which are dry–wet transition zones. The response of EMP's record‐breaking probability to SO is apparent in most regions of China, and its spatial pattern becomes the largest in summer and much smaller in spring and autumn. Copyright © 2012 Royal Meteorological Society
NMR‐based metabonomics detection of differences in the metabolism of hydrolysed versus intact protein of similar amino acid profile
Authors: Hindmarsh Jason P , Awati Ajay , Edwards Patrick JB , Moughan Paul
Published: March 2012

BACKGROUND: Proton nuclear magnetic resonance (NMR)‐based metabonomics has only recently been applied to nutritional research. The limitation of any analytical technique is its sensitivity in detecting the smallest variation. Alterations in nutrition often produce only subtle metabolic modulations. The objective of this study was to determine if NMR‐based metabonomics could detect variations in the metabolic profile of urine from pigs digesting either native casein (NC) or the same casein that had been enzymatically hydrolysed (EHC). NMR permits simultaneous detection of a large number of metabolites, thus allowing detection of unanticipated metabolic fluctuations that may otherwise have gone undetected with the use of only targeted analysis.

RESULTS: Partial least squares discriminant analysis identified significantly (P < 0.05) higher urinary excretions of leucine, valine, taurine and glycine by pigs on the EHC‐based diet.

CONCLUSION: NMR‐based metabonomics is a sensitive method that can uncover unanticipated metabolic changes brought about by physicochemical changes to the feedstock (i.e. hydrolysis). The data show a lower efficiency of retention by the kidney of some amino acids following ingestion of a hydrolysed protein. Copyright © 2012 Society of Chemical Industry
The effect of cocoa, soy, oats and fish oil on metabolic syndrome in rats
Authors: Barrios‐Ramos Juan P , Garduño‐Siciliano Leticia , Loredo Maria , Chamorro‐Cevallos German , Jaramillo‐Flores Maria E
Published: March 2012

BACKGROUND: The effect of functional foods alone or in combination (cocoa + soy + oats + fish oil) on hepatic damage in rats affected with metabolic syndrome was investigated.

RESULTS: Rats that were given cocoa showed a decrease in the levels of triglycerides (TGs) and glucose (63 and 32% respectively) as well as a decrease in blood pressure (15%). Animals fed with soy showed a reduction of 21% in total cholesterol, 15% in blood pressure and 44% in TGs, while feeding oats reduced the concentration of TGs by 53% (P < 0.5). Fish oil caused a reduction in TGs (56%) and glucose (26%). The effect on blood pressure was statistically significant for the groups supplemented with cocoa, soy, cocoa + oats and the total mix. The main finding was a reduction in liver steatosis in animals supplemented with cocoa + oats (from 30 to 4.7% steatosis). Cocoa or fish oil alone did not protect the liver from damage, while cocoa + fish oil did.

CONCLUSION: The most relevant effects were that the cocoa + oats mix decreased steatosis by a very large percentage, as did the cocoa + fish oil mix and the mix of all four functional foods. Copyright © 2012 Society of Chemical Industry
Influence of rootstock on drought response in young ‘Gale Gala’ apple (Malus domestica Borkh.) trees
Authors: Liu Bing‐hua , Cheng Liang , Ma Feng‐wang , Liang Dong , Zou Yang‐jun
Published: March 2012

BACKGROUND: Drought is a major environmental stress limiting plant growth, productivity, and survival worldwide. Rootstocks are widely used to enhance plants resistance to drought stresses. This study determined influence of rootstock on drought responses in 1‐year‐old ‘Gale Gala’ apple trees grafted onto Malus sieversii or M. hupehensis.

RESULTS: Choice of rootstock resulted in differential response to drought stress. Specifically, M. sieversii caused less drought‐induced reduction in relative growth rate, biomass accumulation, leaf area, leaf chlorophyll content, relative water content, photosynthesis rate and maximum chlorophyll fluorescence yield but greater increase in whole‐plant water use efficiency compared to M. hupehensis. Secondly, compared with M. hupehensis, M. sieversii caused less drought‐induced accumulation of reactive oxygen species but more increase in activities of antioxidant enzymes. In addition, xylem sap abscisic acid concentration was greater in trees grafted onto M. hupehensis than in those grafted onto M. sieversii under drought stress.

CONCLUSION: ‘Gale Gala’ trees' response to drought stress was associated with the rootstock's genotype onto which it was grafted. Trees with M. sieversii as rootstock are more drought resistant than trees with M. hupehensis as rootstock, which suggests that M. sieversii can be widely used as rootstock in arid and semi‐arid regions. Copyright © 2012 Society of Chemical Industry
Three‐dimensional optical laser lithography beyond the diffraction limit
Authors: Fischer Joachim , Wegener Martin
Published: March 2012

Direct laser writing has become a versatile and routine tool for the mask‐free fabrication of polymer structures with lateral linewidths down to less than 100 nm. In contrast to its planar counterpart, electron‐beam lithography, direct laser writing also allows for the making of three‐dimensional structures. However, its spatial resolution has been restricted by diffraction. Clearly, linewidths and resolutions on the scale of few tens of nanometers and below are highly desirable for various applications in nanotechnology. In visible‐light far‐field fluorescence microscopy, the concept of stimulated emission depletion (STED) introduced in 1994 has led to spectacular record resolutions down to 5.6 nm in 2009. This review addresses approaches aiming at translating this success in optical microscopy to optical lithography. After explaining basic principles and limitations, possible depletion mechanisms and recent lithography experiments by various groups are summarized. Today, Abbe's diffraction barrier as well as the generalized two‐photon Sparrow criterion have been broken in far‐field optical lithography. For further future progress in resolution, the development of novel tailored photoresists in combination with attractive laser sources is of utmost importance.
A role for the Warburg effect in preimplantation embryo development: Metabolic modification to support rapid cell proliferation
Authors: Krisher Rebecca L. , Prather Randall S.
Published: March 2012

In this essay, we propose that embryos express a metabolic phenotype necessarily different from that of differentiated somatic cells and more like that of rapidly proliferating cancer cells. This metabolic adaptation, known as the Warburg effect, supports rapid cell proliferation. One of the hallmarks of the Warburg effect is that pyruvate is directed away from the tri‐carboxylic acid cycle and metabolized to lactate, resulting in a buildup of glycolytic intermediates. Although this is a comparatively inefficient way to generate ATP, this adaptation allows the cell to meet other critical metabolic requirements, including biomass production and redox regulation. Thus, utilization of WE gives proliferating cells a selective growth advantage. This model represents a completely new understanding of embryo metabolism in the context of a broad, interconnected network of metabolic mechanisms that influence viability, versus the current dogma of carbohydrate metabolism via oxidative phosphorylation. A more complete understanding of embryo metabolism is critical to better support embryo viability in vitro, and to avoid forcing embryos to adapt to suboptimal culture conditions at a significant cost to future growth and development. Mol. Reprod. Dev. 79: 311–320, 2012. © 2012 Wiley Periodicals, Inc.