bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of microRNA‐31 as a novel regulator contributing to impaired interleukin‐2 production in T cells from patients with systemic lupus erythematosus
Authors: Fan Wei , Liang Dong , Tang Yuanjia , Qu Bo , Cui Huijuan , Luo Xiaobing , Huang Xinfang , Chen Shunle , Higgs Brandon W. , Jallal Bahija , Yao Yihong , Harley John B. , Shen Nan
Published: June 2012

Objective

MicroRNAs (miRNAs) function to fine‐tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin‐2 (IL‐2)–related signaling pathways in systemic lupus erythematosus (SLE). The miR‐31 microRNA has been found to be markedly underexpressed in patients with SLE, and thus the present study was undertaken to investigate the role of miR‐31 in IL‐2 defects in lupus T cells.

Methods

Expression levels of miR‐31 were quantitated using TaqMan miRNA assays. Transfection and stimulation of cultured cells followed by TaqMan quantitative polymerase chain reaction, enzyme‐linked immunosorbent assay, and reporter gene assays were conducted to determine the biologic function of miR‐31. NF‐AT nuclear translocation and expression were quantitatively measured using an ImageStream cytometer. Bioinformatics analysis, small interfering RNA (siRNA) knockdown, and Western blotting were performed to validate miR‐31 targets and effects.

Results

The expression of miR‐31 was significantly decreased in lupus T cells, and this was positively correlated with the expression of IL‐2. Overexpression of miR‐31 in T cells increased the production of IL‐2 by altering NF‐AT nuclear expression and IL2 promoter activity, while knockdown of endogenous miR‐31 reduced IL‐2 production. RhoA expression was directly repressed by miR‐31 in T cells. Of note, siRNA‐mediated knockdown of RhoA enhanced IL2 promoter activity and, consequently, up‐regulated IL‐2 production. RhoA expression was consistently up‐regulated and negatively correlated with the levels of miR‐31 in lupus T cells. Manipulation of miR‐31 expression in lupus T cells restored the expression of IL‐2 at both the messenger RNA and protein levels.

Conclusion

MicroRNA‐31 is a novel enhancer of IL‐2 production during T cell activation. Dysregulation of miR‐31 and its target, RhoA, could be a novel molecular mechanism underlying the IL‐2 deficiency in patients with SLE.
B lymphocytes enhance interferon‐α production by plasmacytoid dendritic cells
Authors: Berggren Olof , Hagberg Niklas , Weber Gert , Alm Gunnar V. , Rönnblom Lars , Eloranta Maija‐Leena
Published: June 2012

Objective

The type I interferon (IFN) system and B cells are activated in many autoimmune diseases, such as systemic lupus erythematosus (SLE). The IFNα produced by plasmacytoid dendritic cells (PDCs) stimulates several B cell functions, including autoantibody production. However, not much is known about how B cells influence PDC function. The aim of this study was to investigate the regulatory effect of B cells on IFNα production by PDCs.

Methods

PDCs and B cells isolated from peripheral blood mononuclear cells from healthy blood donors were stimulated with RNA‐containing immune complexes (ICs) consisting of U1 small nuclear RNP and SLE IgG, herpes simplex virus, or oligonucleotide (ODN) 2216, alone or in cocultures. IFNα, several other cytokines, and PDC‐ or B cell–associated surface molecules were analyzed using immunoassays or flow cytometry.

Results

B cells enhanced IFNα production by PDCs up to 47‐fold, and the effect was most pronounced for PDCs stimulated with RNA‐containing ICs. Anti‐CD31 antibody reduced RNA‐containing IC–induced IFNα production by 80% but had no effect on IFNα production when ODN 2216 was used as an inducer. Supernatants from ODN 2216–stimulated B cells promoted IFNα production by PDCs, while supernatants from RNA‐containing IC–stimulated B cells did not.

Conclusion

Our results showed that a novel function of B cells is enhancement of type I IFN production by PDCs. Because B cells are activated by type I IFN, this PDC–B cell cross‐talk might be of fundamental importance in the etiopathogenesis of SLE and contribute to long‐term immune activation in SLE and other systemic rheumatic diseases.
Relationship between inflammation, bone destruction, and osteoproliferation in the HLA–B27/human β2‐microglobulin–transgenic rat model of spondylarthritis
Authors: van Duivenvoorde Leonie M. , Dorris Martha L. , Satumtira Nimman , van Tok Melissa N. , Redlich Kurt , Tak Paul P. , Taurog Joel D. , Baeten Dominique L.
Published: June 2012

Objective

Inhibition of inflammation and destruction, but not of osteoproliferation, in patients with spondylarthritis (SpA) treated with anti–tumor necrosis factor raises the question of how these three processes are interrelated. This study was undertaken to analyze this relationship in a rat model of SpA.

Methods

Histologic spine and joint samples from HLA–B27/human β2‐microglobulin (hβ2m)–transgenic rats were analyzed for signs of spondylitis and destructive arthritis and semiquantitatively scored as showing mild, moderate, or severe inflammation.

Results

In rats exhibiting spondylitis, mildly inflamed sections displayed lymphocyte infiltration in connective tissue adjacent to the junction of the anulus fibrosus and vertebral bone but not at the enthesis. Moderately inflamed tissue samples contained osteoclasts eroding bone outside the cartilage end plate. In sections from rats with severe inflammation, the cartilage end plate and underlying bone marrow were also affected. End‐stage disease was characterized by complete destruction of the intervertebral disc and vertebrae, with ongoing infiltration. Osteoproliferation was not observed in samples from rats with no or mild inflammation, but was present at the edge of the vertebrae in sections with moderate inflammation and persisted during severe inflammation and end‐stage destruction. Osteoproliferation occurred at the border of inflammation, at a distance from bone destruction. A strong correlation between the extent of inflammation, destruction, and osteoproliferation was observed. Sections from rats with arthritis displayed a similar pattern of synovial inflammation associated with bone destruction, and simultaneous but topographically distinct osteoproliferation starting from the periosteum.

Conclusion

SpA in B27/hβ2m–transgenic rats is characterized by destructive inflammatory pannus tissue rather than by enthesitis or osteitis. Destruction and osteoproliferation occur simultaneously but at distinct sites in joints with moderate to severe inflammation.
Modulation of STAT‐3 in rheumatoid synovial T cells suppresses Th17 differentiation and increases the proportion of Treg cells
Authors: Ju Ji Hyeon , Heo Yu‐Jung , Cho Mi‐La , Jhun Joo‐Yeon , Park Jin‐Sil , Lee Seon‐Yeong , Oh Hye‐Jwa , Moon Su‐Jin , Kwok Seung‐Ki , Park Kyung‐Su , Park Sung‐Hwan , Kim Ho‐Youn
Published: June 2012

Objective

To investigate the impact of STAT‐3–mediated regulation on Th17 differentiation in patients with rheumatoid arthritis (RA).

Methods

CD4+ T cells isolated from peripheral blood (PB) and synovial fluid (SF) were stimulated to differentiate into Th17 cells or Treg cells. The activity of STAT‐3 was knocked down by transfecting CD4+ T cells with small interfering RNA (siRNA). After 3 days in culture, the proportions of Th17 cells and Treg cells were measured by flow cytometry, and the production of interleukin‐17 (IL‐17) was measured by reverse transcriptase–polymerase chain reaction and enzyme‐linked immunosorbent assay.

Results

The levels of IL‐17, IL‐6, IL‐23, IL‐1, and tumor necrosis factor α were significantly higher in RA SF and synovial tissue than in SF and synovial tissue from osteoarthritis patients. In RA synovial tissue, the expression of STAT‐3 increased in proportion to the severity of synovitis, as shown by stromal cellularity, intimal hyperplasia, and inflammatory infiltration. The degree of Th17 differentiation was highest in RA SF, followed by RA PB, and lowest in normal subjects. In CD4+ T cells, transfection with STAT‐3 siRNA prevented Th17 differentiation of mononuclear cells from RA PB and SF but increased the proportion of Treg cells. In contrast, inhibition of STAT‐5, the transcription factor for Treg cells, increased the proportion of Th17 cells and reduced that of Treg cells.

Conclusion

Our findings indicate that modulation of STAT‐3 in CD4+ T cells affects the differentiation of Th17 cells and Treg cells in patients with RA. This role of STAT‐3 in RA synovial T cells may provide a new therapeutic target for the management of RA.
Dkk‐1 promotes angiogenic responses and cartilage matrix proteinase secretion in synovial fibroblasts from osteoarthritic joints
Authors: Weng Lin‐Hsiu , Ko Jih‐Yang , Wang Ching‐Jen , Sun Yi‐Chih , Wang Feng‐Sheng
Published: June 2012

Objective

Synovial hypervascularity is a prominent pathologic feature in osteoarthritic (OA) joints. Wnt inhibitor Dkk‐1 contributes to joint remodeling. We undertook this study to investigate whether Dkk‐1 regulates cartilage destruction activities in OA synovial fibroblasts.

Methods

Synovial tissues were harvested from knees of patients with OA and from injured knees of non‐OA patients who underwent arthroscopy. Expression of Dkk‐1, angiogenic factors (stromal cell–derived factor 1 and colony‐stimulating factor 1), and cartilage proteinases (ADAMTS‐5 and matrix metalloproteinase 3 [MMP‐3]) as well as vascularity in synovium and synovial fluid were quantified using enzyme‐linked immunosorbent assay, reverse transcription–polymerase chain reaction, and histomorphometry. Synovial fibroblasts were treated with interleukin‐1β (IL‐1β), anti–Dkk‐1 antibody, and RNA interference to characterize their angiogenic activity. Rats with OA knees were administered Dkk‐1 antisense oligonucleotide to verify synovial angiogenesis and cartilage integrity.

Results

OA synovium exhibited increased vascularity and expression of angiogenic factors and proteinases in association with up‐regulated Dkk‐1 levels. Neutralizing Dkk‐1 reduced the inhibitory effects of OA synovial fluid on aggrecan expression in chondrocyte cultures. IL‐1β induction of Dkk‐1 increased expression of hypoxia‐inducible factor 1α (HIF‐1α), angiogenic factors, ADAMTS‐5, and MMP‐3 in synovial fibroblasts and promoted angiogenesis in vascular endothelial cells. Knockdown of HIF‐1α decreased Dkk‐1 enhancement of angiogenic factor expression. Stabilization of glycogen synthase kinase 3β phosphorylated at Ser9, β‐catenin, T cell factor 4, and ERK signaling attenuated Dkk‐1 up‐regulation of angiogenic factor and proteinase expression in synovial fibroblasts. In vivo, Dkk‐1 interference reduced the expression of angiogenic factors and proteinases and ameliorated synovial vascularity and cartilage deterioration in knees of rats with OA.

Conclusion

Dkk‐1 promoted angiogenic and cartilage degradation activities in synovial fibroblasts, which accelerated synovial angiogenesis and cartilage destruction. Dkk‐1 blockade has therapeutic potential for reducing OA‐induced synovitis and joint deterioration.
Anatomical Sciences Education Vol. 5, Issue 4, 2012 Cover Image
Authors: Ang Eng‐Tat , Sugand Kapil , Hartman Mikael , Seow Choon‐Sheong , Bay Boon‐Huat , Abrahams Peter
Published: July 2012

A group of first year medical students at the Yong Loo Lin School of Medicine of the National University of Singapore study anatomy in the Anatomy Museum at this institution. Using an anatomical model, students discuss the extraocular muscles with their lecturers Drs. Boon‐Huat Bay (center) and Eng‐Tat Ang (third from left). In this issue of ASE, Dr. Ang and his colleagues review the past, present, and future of anatomy education in Singapore's three medical schools.
ε‐Optimal Value and Approximate Multidimensional Dual Dynamic Programming
Authors: Nowakowski A.
Published: June 2012

This paper develops an approximate dual dynamic programming for an ε− optimal multidimensional control problem governed by first order hyperbolic equations. The problem considered is of the Dieudonne‐Rashevsky type and contains as a particular case class‐qualified deposit and Capital theory problems. It is proven that each Lipschitz continuous function satisfying the dual Hamilton‐Jacobi inequality can be used to define an ε‐optimal value.
Iterative Learning Control for Nonlinear Systems: A Bounded‐Error Algorithm
Authors: Delchev Kamen
Published: June 2012

This paper presents a nonlinear iterative learning control (NILC) for nonlinear time‐varying systems. An algorithm of a new strategy for the NILC implementation is proposed. This algorithm ensures that trajectory‐tracking errors of the proposed NILC, when implemented, are bounded by a given error norm bound. A special feature of the algorithm is that the trial‐time interval is finite but not fixed as it is for the other iterative learning algorithms. A sufficient condition for convergence and robustness of the bounded‐error learning procedure is derived. With respect to the bounded‐error and standard learning processes applied to a virtual robot, simulation results are presented in order to verify maximal tracking errors, convergence and applicability of the proposed learning control.
Loop‐Shaping and Easy Tuning of Fractional‐Order Proportional Integral Controllers for Position Servo Systems
Authors: Lino P. , Maione G.
Published: June 2012

This paper develops simple formulas directly relating performance specifications to control parameters of fractional‐order proportional integral (PI) controllers for position servo systems. With the proposed controller settings, the open‐loop frequency response achieves a good phase margin, that remains constant in a wide range around the crossover frequency. Consequently, the tuning results in high stability robustness to gain variations in the loop. Moreover, the fractional order integration also leads to limited overshoot and short settling time. Laboratory experiments confirm simulation results.
Einsatz von technischen Textilien für den mobilen Hochwasserschutz
Authors: Heinlein Kai , Wagner Rosemarie
Published: July 2012

Der Einsatz von technischen Textilien für den mobilen Hochwasserschutz eignet sich hervorragend, vor allem wenn eine geringe Vorwarnzeit im notfallmäßigen Hochwasserfall besteht. In diesem Beitrag werden die Grundlagen des textilen Hochbaus (textile Überdachungen von Stadien und Schwimmhallen) auf die Entwicklung wassergefüllter Schutzsysteme als Alternative zu Sandsacksystemen übertragen. Es wird gezeigt, dass die Untersuchungen zum Materialverhalten von beschichteten Geweben und das typische Vorgehen bei Membrankonstruktionen in der Architektur, wie Formfindung, statische Berechnung und Zuschnitt für die Auslegung von mobilen Hochwasserschutzsystemen angewendet werden können. Im Folgenden wird dargestellt, wie diese methodische Vorgehensweise ein geeignetes Werkzeug für die Planung von zwei ausgewählten Hochwasserschutzsystemen ist und auf die speziellen Anforderungen angepasst wird. Es wird die Formfindung von Membranhüllen unter hydrostatischer Belastung näher beschrieben und eine statische Analyse eines solchen Systems veranschaulicht. Die Vorgehensweise zur Simulation solcher Probleme anhand eines tragwerksplanerischen Computerprogramms, durch Erweiterung der Randbedingungen mit dem Einsatz von Zusatztools, wird vorgestellt. Die Richtigkeit der Vorgehensweise wird durch experimentelle Verifizierung der Simulationsergebnisse sichergestellt.

Mobile flood protection by use of technical textiles

The use of technical textiles for mobile flood protection is excel, especially if there is a short warning time in case of emergency flood events. This paper describes the transmission of textile building construction basics (textile roofs of stadiums and swimming pools) to the development of water‐filled protection systems as an alternative to sand bag systems. It is shown that the investigations of material behavior of coated fabrics and the typical approach of membrane structures in architecture, such as form‐finding, structural analysis and cutting pattern can be used to develop mobile flood protection systems. The following article manifests how this methodological approach is a suitable tool for the design of two selected flood control systems and is adapted to the specific requirements. The requirements and the selection of applicable materials, technical textiles in particular, are discussed. It describes the form finding of membrane shells under hydrostatic stress and illustrates in detail a static analysis of such a system. The procedure of the simulation of such problems by means of a supporting structure planning computer program will be presented by expanding the boundary conditions with the use of additional tools. The correctness of the procedure is ensured by experimental verification of the simulation results.
Neurodevelopmental outcomes following prenatal exposure to serotonin reuptake inhibitor antidepressants: A “social teratogen” or moderator of developmental risk?
Authors: Hanley Gillian E. , Oberlander Tim F.
Published: June 2012

Understanding how prenatal serotonin reuptake inhibitors (SRIs) influence early brain development can provide critical clues to how early life experience programs developing neural systems that might contribute to risks for illness across the life span. To date, no gross SRI‐related neuroteratogenic effects have been identified, but evidence of subtle functional behavioral disturbances associated with fetal SRI exposure are emerging. Although some outcomes reflect a “main effect” for the SRI exposure, childhood development beyond infancy appears typical or continues to be influenced by life with a mother with a mood disturbance. Research shows that not all infants and children are equally affected; thus appreciating the effects of prenatal and postnatal maternal mental illness and of genetic variations that influence early serotonin signaling offers critical new insights into factors that contribute to developmental risk, plasticity, and resiliency in children with prenatal SRI exposure. Such a developmental perspective should lead us to understand what heightens or lessens neurodevelopmental vulnerability, thereby optimizing maternal pharmacotherapy and identifying who benefits and is least likely to experience neurobehavioral disturbances. Birth Defects Research (Part A) 94:651–659, 2012. © 2012 Wiley Periodicals, Inc.
Endogenous retroviruses in mammals: An emerging picture of how ERVs modify expression of adjacent genes
Authors: Isbel Luke , Whitelaw Emma
Published: June 2012

Endogenous retrovirsuses (ERVs) have long been known to influence gene expression in plants in important ways, but what of their roles in mammals? Our relatively sparse knowledge in that area was recently increased with the finding that ERVs can influence the expression of mammalian resident genes by disrupting transcriptional termination. For many mammalian biologists, retrotransposition is considered unimportant except when it disrupts the reading frame of a gene, but this view continues to be challenged. It has been known for some time that integration into an intron can create novel transcripts and integration upstream of a gene can alter the expression of the transcript, in many cases producing phenotypic consequences and disease. The new findings on transcriptional termination extend the opportunities for retrotransposons to play a role in human disease.
Luminescence properties of Tb3+ doped Sr2SnO4 green phosphor in UV/VUV regions
Authors: Srinivas M , Rao B Appa , Vithal M , Rao P Raghava
Published: June 2012

Polycrystalline Sr2SnO4 phosphors doped with Tb3+ were prepared by conventional solid‐state reaction method. Materials were characterized by powder XRD and EDS techniques. The luminescence properties of these materials were investigated under UV and VUV excitation. Upon excitation at 272 nm, phosphors exhibited intense emissions at 492 and 543 nm due to 5D4 → 7 F6 and 5D4 → 7 F5 transitions of Tb3+ ions, respectively. Materials also exhibited strong emissions from these transitions under VUV excitation at 147, 173 and 230 nm. Quantitative analysis of the spectra indicated probable applications of these phosphors for PDP and other display devices as green emitting phosphors. Copyright © 2012 John Wiley & Sons, Ltd.
Ionic liquids dispersive liquid–liquid microextraction and high‐performance liquid chromatographic determination of irbesartan and valsartan in human urine
Authors: Li Zhiling , Chen Fan , Wang Xuedong , Wang Chengjun
Published: June 2012

An environmentally friendly ionic liquids dispersive liquid–liquid microextraction (IL‐DLLME) method coupled with high‐performance liquid chromatography (HPLC) for the determination of antihypertensive drugs irbesartan and valsartan in human urine samples was developed. The HPLC separations were accomplished in less than 10 min using a reversed‐phase C18 column (250 × 4.60 mm i.d., 5 µm) with a mobile phase containing 0.3 % formic acid solution and methanol (v/v, 3:7; flow rate, 1.0 mL/min). UV absorption responses at 236 nm were linear over a wide concentration range from 50 µg/mL to the detection limits of 3.3 µg/L for valsartan and 1.5 µg/L for irbesartan. The effective parameters on IL‐DLLME, such as ionic liquid types and their amounts, disperser solvent types and their volume, pH of the sample and extraction time were studied and optimized. The developed IL‐DLLME‐HPLC was successfully applied for evaluation of the urine irbesartan and valsartan profile following oral capsules administration. Copyright © 2012 John Wiley & Sons, Ltd.
Substrates of neuropsychological functioning in stimulant dependence: a review of functional neuroimaging research
Authors: Crunelle Cleo L. , Veltman Dick J. , Booij Jan , van Emmerik – van Oortmerssen Katelijne , van den Brink Wim
Published: June 2012

Stimulant dependence is associated with neuropsychological impairments. Here, we summarize and integrate the existing neuroimaging literature on the neural substrates of neuropsychological (dys)function in stimulant dependence, including cocaine, (meth‐)amphetamine, ecstasy and nicotine dependence, and excessive caffeine use, comparing stimulant abusers (SAs) to nondrug using healthy controls (HCs). Despite some inconsistencies, most studies indicated altered brain activation in prefrontal cortex (PFC) and insula in response to reward and punishment, and higher limbic and anterior cingulate cortex (ACC)/PFC activation during craving and attentional bias paradigms in SAs compared with HCs. Impulsivity in SAs was associated with lower ACC and presupplementary motor area activity compared with HCs, and related to both ventral (amygdala, ventrolateral PFC, insula) and dorsal (dorsolateral PFC, dorsal ACC, posterior parietal cortex) systems. Decision making in SAs was associated with low dorsolateral PFC activity and high orbitofrontal activity. Finally, executive function in SAs was associated with lower activation in frontotemporal regions and higher activation in premotor cortex compared with HCs. It is concluded that the lower activations compared with HCs are likely to reflect the neural substrate of impaired neurocognitive functions, whereas higher activations in SAs compared with HCs are likely to reflect compensatory cognitive control mechanisms to keep behavioral task performance to a similar level as in HCs. However, before final conclusions can be drawn, additional research is needed using neuroimaging in SAs and HCs using larger and more homogeneous samples as well as more comparable task paradigms, study designs, and statistical analyses.
Prevalence, laterality, and comorbidity of hippocampal sclerosis in an autopsy sample
Authors: Zarow Chris , Weiner Michael W. , Ellis William G. , Chui Helena Chang
Published: June 2012

Hippocampal sclerosis (HS) is a common and often asymmetric neuropathological finding among elderly persons who experience progressive memory loss, but its cause is unknown and it is rarely diagnosed during life. In order to improve both understanding and diagnosis of late‐life HS, bilateral hippocampi and cerebral hemispheres were reviewed in 130 consecutive autopsy cases drawn from a longitudinal study of subjects with subcortical ischemic vascular dementia (IVD), Alzheimer disease (AD) and normal aging. HS was found in 31 of 130 cases (24.5%). Of these, 45% were bilateral, 32% left‐sided, and 23% right‐sided. The majority of HS cases involved the entire rostral‐caudal extent of the hippocampus. However, in 7 cases HS was focal in nature and was only found at or anterior to the lateral geniculate nucleus. In 77% of cases, HS was accompanied by other types of pathology (‘mixed’ HS), but in 23% of cases it was the sole neuropathologic finding (‘pure’ HS). TDP‐43‐positive cytoplasmic inclusions were found in dentate granule cells in 93% of all HS cases, 55% of AD cases with no HS, but 0% of IVD cases with no HS. MRI hippocampal volumes were significantly lower in bilateral HS compared to AD (p < 0.001) and in unilateral HS cases compared to cases with intact hippocampi (p < 0.001).

Since HS may occur unilaterally in approximately a quarter of cases, its prevalence may be underestimated if only one cerebral hemisphere is examined. The presence of TDP‐43 inclusions in HS cases, regardless of accompanying pathologies (e.g., AD, IVD, FTLD), is consistent with an underlying neurodegenerative pathogenetic mechanism. Further studies are warranted to determine whether greater severity of hippocampal atrophy on MRI may assist the clinical differentiation of HS from AD.
A promising randomized trial of a new therapy for obsessive–compulsive disorder
Authors: Hu Xian‐Zhang , Wen You‐Sheng , Ma Jian‐Dong , Han Dong‐Ming , Li Yu‐Xia , Wang Shu‐Fan
Published: June 2012

Pharmacotherapy and cognitive–behavioral therapy (CBT) are currently the most effective interventions for treating obsessive–compulsive disorder (OCD). These treatments, however, are time consuming and in some cases the patients do not show significant improvement. In all, 30%–60% of OCD patients do not respond adequately to pharmacotherapy and 20%–40% of OCD patients who complete CBT do not improve significantly, suggesting a more efficacious approach is needed. The objectives of this study are to demonstrate an efficacious pharmacotherapy plus psychotherapy, named cognitive–coping therapy (CCT), for OCD and to investigate the efficacy of this approach in a larger sample size. Therefore, a total of 108 patients with OCD were randomly allocated into three groups: pharmacotherapy (N = 38), pharmacotherapy plus CBT (PCBT, N = 34), and pharmacotherapy plus CCT (PCCT, N = 36). The severity of symptoms and the patients' functioning were assessed pretreatment and after 7, 14, 21 days, and 1‐, 3‐, 6‐, and 12‐month treatment using the Yale‐Brown Obsessive Compulsive Scale and Global Assessment of Functioning (GAF). Compared with the pharmacotherapy and PCBT groups, the severity of OCD symptoms was significantly reduced (P < 0.001), the rates of response (100%) and remission (85.0%) were significantly higher (P < 0.001), and relapse rate was lower (P = 0.017) in PCCT group during the 1‐year follow‐up. In addition, the GAF score was significantly higher in the PCCT group than in the other two groups (P < 0.001). Our preliminary data suggest that PCCT is a more efficacious psychotherapy for OCD patients than pharmacotherapy or PCBT.
A novel DrosophilaSOD2 mutant demonstrates a role for mitochondrial ROS in neurodevelopment and disease
Authors: Celotto Alicia M. , Liu Zhaohui , VanDemark Andrew P. , Palladino Michael J.
Published: June 2012

Reactive oxygen species (ROS) play essential roles in cell signaling, survival, and homeostasis. Aberrant ROS lead to disease and contribute to the aging process. Numerous enzymes and vigilant antioxidant pathways are required to regulate ROS for normal cellular health. Mitochondria are a major source of ROS, and mechanisms to prevent elevated ROS during oxidative phosphorylation require super oxide dismutase (SOD) activity. SOD2, also known as MnSOD, is targeted to mitochondria and is instrumental in regulating ROS by conversion of superoxides to hydrogen peroxide, which is further broken down into H2O and oxygen. Here, we describe the identification of a novel mutation within the mitochondrial SOD2 enzyme in Drosophila that results in adults with an extremely shortened life span, sensitivity to hyperoxia, and neuropathology. Additional studies demonstrate that this novel mutant, SOD2bewildered, exhibits abnormal brain morphology, suggesting a critical role for this protein in neurodevelopment. We investigated the basis of this neurodevelopmental defect and discovered an increase in aberrant axonal that could underlie the aberrant neurodevelopment and brain morphology defects. This novel allele, SOD2bewildered, provides a unique opportunity to study the effects of increased mitochondrial ROS on neural development, axonal targeting, and neural cell degeneration in vivo.
Dietary modification of metabolic pathways via nuclear hormone receptors
Authors: Caiozzi Gianella , Wong Brian S. , Ricketts Marie‐Louise
Published: July 2012

Nuclear hormone receptors (NHRs), as ligand‐dependent transcription factors, have emerged as important mediators in the control of whole body metabolism. Because of the promiscuous nature of several members of this superfamily that have been found to bind ligand with lower affinity than the classical steroid NHRs, they consequently display a broader ligand selectivity. This promiscuous nature has facilitated various bioactive dietary components being able to act as agonist ligands for certain members of the NHR superfamily. By binding to these NHRs, bioactive dietary components are able to mediate changes in various metabolic pathways, including, glucose, cholesterol and triglyceride homeostasis among others. This review will provide a general overview of the nuclear hormone receptors that have been shown to be activated by dietary components. The physiological consequences of such receptor activation by these dietary components will then be discussed in more detail. Copyright © 2012 John Wiley & Sons, Ltd.
Molecular Understanding of Enyne Hydrogenation over Palladium and Copper Catalysts
Authors: Bridier Blaise , Karhánek David , Pérez‐Ramírez Javier , López Núria
Published: June 2012

Partial hydrogenation of unsaturated hydrocarbons comprises an important family of reactions that are applied in many industrial sectors. Understanding the hydrogenation of polyunsatured and polyunsaturated compounds on heterogeneous catalysts at its molecular level remains a challenging milestone to fine‐tune the product distribution. Our study presents a detailed mechanistic analysis of the gas phase hydrogenation of vinylacetylene (1‐butene‐3‐yne) and valylene (2‐methyl‐1‐butene‐3‐yne) over palladium and copper catalysts. These two metals are selected owing to their pronounced differences in continuous flow catalytic tests at ambient pressure. The chemoselectivity, regioselectivity, isomerization, and oligomerization patterns measured in a broad range of feed hydrogen/hydrocarbon ratios are rationalized by density functional theory simulations. An extended Brønsted–Evans–Polanyi relationship for both substrates and active metals is found for the hydrogenation processes. The identified factors that govern selectivity are similar to those identified for smaller C2 and C3 compounds and, thus, a means of systematization to other polyunsaturated compounds is opened up.
High‐Surface‐Area SiO2–ZrO2 Mixed Oxides as Catalysts for the Friedel–Crafts‐Type Alkylation of Arenes with Alcohols and Tandem Cyclopropanation Reactions
Authors: Kaper Helena , Bouchmella Karim , Mutin P. Hubert , Goettmann Frédéric
Published: July 2012

The catalytic activity of SiO2–ZrO2 mixed oxides was studied for the Friedel–Crafts‐alkylation reaction between anisole and benzylic or allylic alcohols. In particular, the influence of Zr content on the catalytic activity was studied. The catalyst with the lowest Zr content (5 mol % ZrO2) showed the highest activity with high selectivity for the alkylated product and good recyclability. We used this catalyst in the reaction of 1‐phenyl‐1‐ethanol with toluene and xylene. We also studied the possibility of a tandem process that involved a Friedel–Crafts alkylation and the subsequent trans‐hydrogenation of trans‐1,3‐diphenyl‐2‐propen‐1‐ol for the synthesis of substituted cyclopropanes.
Microfluidic Solvent Extraction of Metal Ions and Complexes from Leach Solutions Containing Nanoparticles
Authors: Priest C. , Zhou J. , Klink S. , Sedev R. , Ralston J.
Published: June 2012

Solvent extraction is often hindered by the presence of particles and surfactants that increase the stability of emulsion phases, i.e., crud, thus preventing full recovery of the organic phase and the valuable metal species. It is shown that bypassing the formation of a particle‐stabilized crud using a stream‐based microfluidic extraction approach has great potential for handling these more challenging and industry‐relevant systems provided sufficient throughputs can be realized. Metal ions and complexes are extracted from copper oxide and chromite leach solutions at high efficiencies and extraction rates within the confinement of a microchannel and in the presence of silica nanoparticles. These findings and their implications for process intensification are discussed.
Chemical Looping Dry Reforming as Novel, Intensified Process for CO2 Activation
Authors: Bhavsar S. , Najera M. , Veser G.
Published: June 2012

Chemical looping dry reforming (CLDR) is a novel, intensified route for CO2 activation. Two nanostructured carriers (Fe‐BHA and Fe@SiO2) are synthesized, characterized, and evaluated with regard to activity and stability in thermogravimetric and fixed‐bed CLDR reactor studies over a temperature range of ~500–800 °C. Fe‐barium hexaaluminate (Fe‐BHA) shows fast redox kinetics and stable operation over multiple CLDR cycles, while Fe@SiO2 exhibits poor activity for CO generation due to a partial loss of the core‐shell structure and formation of silicates. While the latter could be removed via a two‐step oxidation scheme, carrier utilization remained well below that of Fe‐BHA (~ 51 % versus ~ 15 %). However, the two‐step oxidation configuration turns the net endothermic CLDR process into a net exothermic process, opening up a highly efficient autothermal process alternative.
Dispersion Characteristics and Mass Transfer in a Pilot‐Scale Gas‐Liquid Oscillatory‐Plate Column
Authors: Gomaa H. G. , Hashem N. , Al‐Taweel A. M.
Published: June 2012

Mass transfer and hydrodynamic characteristics of an oscillatory‐plate column (OPC) and their relation to energy dissipation were investigated using a 0.1‐m diameter pilot‐scale unit. The column is characterized by having plates with a small hole diameter (1.6–3.2 mm) oscillating at 180° out of phase at higher frequencies (0–30 Hz) and small amplitudes (0–3.2 mm). Using this design, it was possible to achieve gas holdup and specific interfacial areas as high as ∼0.8 and 400 m–1, respectively. The maximum gas superficial velocity achieved reaches as high as 1.7 m/s, while the axial dispersion coefficient ranged from ∼10–4 to over ∼3 × 10–3 m2s–1, which is almost one order of magnitude lower than that in bubble columns under similar flow rates. The value of gas velocity of ∼0.1 m s–1 seems to mark a transition beyond which interfacial area, holdup, and axial mixing become practically unchanged. Keeping in view its performance characteristics, the column can satisfactorily meet many of the demands posed by intensified wastewater treatment processes, namely high rates of oxygen transfer, multistage operational mode, uniform distribution of small‐scale turbulence structure, and the ability to handle sludge with relatively high concentrations of suspended solids.
Design of a Pervaporation Photocatalytic Reactor for Process Intensification
Authors: Camera‐Roda G. , Santarelli F.
Published: June 2012

The process intensification obtainable in an integrated photocatalysis‐pervaporation process can be significant, but it depends largely on the correct design of the system. Starting from the kinetic analysis of the photocatalytic reaction, the dimensions and the operative conditions of the photoreactor must be chosen to effectively utilize the radiant energy and the volume of the reactor. Then, the effects of the parameters pertinent to the integrated process are studied and discussed to ascertain the optimum values that enhance the yields in the photocatalytic synthesis of a chemical compound.
Micromixing Characteristics in a Small‐Scale Spinning Disk Reactor
Authors: Boodhoo K. V. K. , Al‐Hengari S. R.
Published: June 2012

Thin films formed under high acceleration fields in a spinning disk reactor (SDR) are characterized by high shear rates and intense surface ripples which are known to play an important role in improving the selectivity, yield, and final product quality in many mixing‐dependent processes. The micromixing efficiency of a small‐scale SDR of 10 cm disk diameter for a range of hydrodynamic conditions by means of the iodide‐iodate test reaction is determined. Under optimized conditions, the SDR exhibits a better micromixing performance than the mechanically stirred vessel and other continuous intensified reactors, such as the rotating packed bed, when processing water‐like fluids at the highest investigated flow rate of 5 mL s–1. These results highlight the potential of the SDR as an alternative intensified mixer/reactor for processes where a high degree of mixing is desirable.
Process Intensification in Stirred Tanks
Authors: Wu J. , Nguyen B. , Lane G. , Wang S. , Parthasarathy R. , Graham L. J.
Published: June 2012

A summary of methods for process intensification in stirred reactors is presented, based mainly on the experience from R&D in the minerals processing industry. The process intensification concept is broadened to include innovations which lead to dramatically increased throughput for large‐scale processing reactors, in contrast to the traditional definition of reactor size reduction, which has so far been ignored by the minerals industry. Methods enabling operating at high solids concentrations in processing tanks are reviewed to increase the throughput. It is proposed that the agitation power constraint at a high solids loading can be overcome by removal of baffles, for slowly reacting slurry systems typical in minerals processing. It is also suggested that the difficulty of pumping of high‐concentration slurry feed can be overcome by operating with stratification, such that the solids residence time is made longer than the bulk flow residence time. Production loss through tank downtime is common in the mineral process industry, thus, a need to reduce the tank downtime should not be underestimated in the context of process intensification. Methods including the swirl flow technology developed by CSIRO and Queensland Alumina Ltd in Australia to suppress the scaling growth, and agitator design principles to reduce erosion are introduced. Enhanced mass transfer toward process intensification is also discussed.
Multiscale Aspects of Modeling Gas‐Phase Nanoparticle Synthesis
Authors: Buesser B. , Gröhn A. J.
Published: June 2012

Aerosol reactors are utilized to manufacture nanoparticles in industrially relevant quantities. The development, understanding, and scale‐up of aerosol reactors can be facilitated with models and computer simulations. An overview of recent developments of models and simulations is presented and their interconnection in a multiscale approach is discussed. A short introduction of the various aerosol reactor types and gas‐phase particle dynamics is provided as a background for the later discussion of the models and simulations. Models are presented with decreasing time and length scales in sections on continuum, mesoscale, molecular dynamics, and quantum mechanics models.
Rapid Production of Biodiesel in Mesoscale Oscillatory Baffled Reactors
Authors: Phan A. N. , Harvey A. P. , Eze V.
Published: June 2012

Continuous alkali‐catalyzed transesterification of rapeseed oil with methanol was carried out in three mesoreactor designs. The induction time decreased with oscillatory Reynolds number for all three reactors. Stable steady states were achieved within induction times of 1.5, 2.5, and 4.0 residence times for the integral, wire wool, and helical baffle designs, respectively. Both experimental and simulated results indicated that under the given conditions there is an optimal residence time for homogeneous transesterification. Higher residence times resulted in reduced fatty acid methyl ester content due to the saponification side reaction. The results demonstrate that biodiesel can be produced at an industrially acceptable level of conversion (> 95 %) in < 5 min residence time. This requires a combination of high catalyst concentration and good mixing.
Process Intensification of Emulsion Polymerization Using a Compartment Reactor
Authors: Ohmura N. , Horie T. , Kumagai N. , Esaki T. , Yamazaki T.
Published: June 2012

Attempts were made to intensify continuous emulsion polymerization using a compartment reactor consisting of three well‐mixing compartments. The goal of this intensification is to obtain a stable and monodisperse particle size as well as high monomer conversion, by controlling the mixing under continuous operation. A two‐bladed paddle impeller was used in the first compartment to intensify the dispersibility and reactivity in the aqueous phase, while a rotating disk was used in the third compartment to avoid excessive flocculation of the polymer particles. In the second compartment, a two‐bladed turbine impeller or a rotating disk was used. The compartment reactor successfully obtained much higher monomer conversion and also more stable and monodisperse particles than a single continuous stirred‐tank reactor. The oscillations of the mean particle size were greatly suppressed by spatially different mixing operations.
Potential Analysis of Smart Flow Processing and Micro Process Technology for Fastening Process Development: Use of Chemistry and Process Design as Intensification Fields
Authors: Hessel V. , Vural Gürsel I. , Wang Q. , Noël T. , Lang J.
Published: June 2012

Flow processes with microstructured reactors allow paradigm changes in process development and thus can enable a faster development time to the final production plant. They do this by exploiting similarity effects along the development chain (modularity) and intensification. The final result can be a (significantly) reduced number of apparatus in the plant, a (significantly) reduced apparatus size, and a higher predictability in the scale‐out of the apparatus. So far, this was mainly achieved via transport intensification given in microstructured reactors – improved mixing and heat transfer which increase productivity and possibly improve selectivity. A more new idea is chemical intensification through deliberate use of harsh chemistries at unusual (high) pressure, temperature, concentration, and reaction environment which again increases productivity. A very new idea is the process design intensification – the reaction‐maximized flow processes need less separation expenditure and the small unit size together with the high degree in functionality gives large potential for system integration. Both means change and simplify the process scheme totally which can lead to a reduced number of apparatus and has impact on predictability. The modular nature of the small flow units allow an easy implementation to modern modular plant environments (Future Factories) which enables to perform all the testing cycles (lab, pilot, production) in one plant environment; an example are here container plants. All these measures have large potential for (much) decreased overall development time.
Semicontinuous Thermal Separation Systems
Authors: Adams T. A. , Pascall A.
Published: June 2012

Since the year 2000, semicontinuous separation processes have been studied as a unique process intensification technique for the thermal separation of chemical mixtures. Typically, a single separation unit is used for multiple purposes with the aid of an auxiliary storage tank called a middle vessel. The system is operated cyclically but without startup or shutdown phases. As a result, multiple separation steps can be carried out with fewer capital expenses. In several cases, a significant profitability advantage over continuous or batch process alternatives has been shown, particularly for intermediate production capacities. The progress in semicontinuous systems is reviewed, including the development of semicontinuous ternary distillation, liquid‐liquid extraction, azeotrope distillation, reactive distillation, and semicontinuous systems with integrated reaction and distillation or extraction. Control and operational strategies for semicontinuous systems are reviewed, as well as heuristics for modeling and simulation.
Scalable Syntheses of Both Enantiomers of DNJNAc and DGJNAc from Glucuronolactone: The Effect of N‐Alkylation on Hexosaminidase Inhibition
Authors: Glawar Andreas F. G. , Best Daniel , Ayers Benjamin J. , Miyauchi Saori , Nakagawa Shinpei , Aguilar‐Moncayo Matilde , García Fernández José M. , Ortiz Mellet Carmen , Crabtree Elizabeth V. , Butters Terry D. , Wilson Francis X. , Kato Atsushi , Fleet George W. J.
Published: June 2012

The efficient scalable syntheses of 2‐acetamido‐1,2‐dideoxy‐D‐galacto‐nojirimycin (DGJNAc) and 2‐acetamido‐1,2‐dideoxy‐D‐gluco‐nojirimycin (DNJNAc) from D‐glucuronolactone, as well as of their enantiomers from L‐glucuronolactone, are reported. The evaluation of both enantiomers of DNJNAc and DGJNAc, along with their N‐alkyl derivatives, as glycosidase inhibitors showed that DGJNAc and its N‐alkyl derivatives were all inhibitors of α‐GalNAcase but that none of the epimeric DNJNAc derivatives inhibited this enzyme. In contrast, both DGJNAc and DNJNAc, as well as their alkyl derivatives, were potent inhibitors of β‐GlcNAcases and β‐GalNAcases. Neither of the L‐enantiomers showed any significant inhibition of any of the enzymes tested. Correlation of the in vitro inhibition with the cellular data, by using a free oligosaccharide analysis of the lysosomal enzyme inhibition, revealed the following structure–property relationship: hydrophobic side‐chains preferentially promoted the intracellular access of iminosugars to those inhibitors with more‐hydrophilic side‐chain characteristics.