bluuebunny/crossref_metadata_2025 huggingface dataset:
Hominoid dispersal patterns and human evolution
Authors: Koenig Andreas , Borries Carola
Published: June 2012

Recent advances in DNA and isotope analyses have allowed tentative reconstructions of dispersal strategies of Plio‐Pleistocene hominins.1, 2 Comparing their findings to dispersal patterns of some extant apes and humans suggested groups of related males and unrelated females in Neandertals indicating patrilocality2 and Pan‐like male philopatry in australopiths.1 Here we review the demographic, ethnographic, and genetic evidence of dispersal patterns in extant apes and humans and compare the results to the suggestions for Plio‐Pleistocene hominins. We find that alternative dispersal patterns, for example among gorillas or gibbons, could explain the findings of related or natal males in a confined geographic area. Based on sexual size dimorphism, we speculate that gorillas might currently be the best model for reconstructing dispersal in robust australopiths. Given that the sexual size dimorphism in other australopiths is still hotly debated, the question of which hominoid model best matches their dispersal pattern must remain unanswered. Neandertal dispersal patterns have been compared to patrilocality of modern humans. However, the latter is related to the advent of food production. Consequently, hunter‐gatherers exhibiting primarily multilocality appear to be the better comparison for Neandertals. Overall, human‐like patrilocality and Pan‐like male philopatry appear to be poor models for the reconstruction of dispersal patterns in Plio‐Pleistocene hominins. © 2012 Wiley Periodicals, Inc.
The status of Homo heidelbergensis (Schoetensack 1908)
Authors: Stringer Chris
Published: June 2012

The species Homo heidelbergensis is central to many discussions about recent human evolution. For some workers, it was the last common ancestor for the subsequent species Homo sapiens and Homo neanderthalensis; others regard it as only a European form, giving rise to the Neanderthals. Following the impact of recent genomic studies indicating hybridization between modern humans and both Neanderthals and “Denisovans”, the status of these as separate taxa is now under discussion. Accordingly, clarifying the status of Homo heidelbergensis is fundamental to the debate about modern human origins. © 2012 Wiley Periodicals, Inc.
On the signal degradation induced by the interpolation and the sampling rate reduction in aeroacoustics hybrid methods
Authors: Cunha G. , Redonnet S.
Published: June 2012

Taking place within more extensive work that focuses on hybrid methods in aeroacoustics, the present study is devoted to the data transfer operations that are to be performed between two stages of a hybrid calculation. More precisely, the article focuses on two typical operations that usually accompany such data transfer, which are (i) the sampling rate reduction and (ii) the interpolation of the unsteady perturbations to be transmitted from one stage to the other. First part of the paper analyzes the two main issues of such operations, which are the spuriousing and the aliasing phenomena. For doing so, the usual notions of the interpolation theory are revisited before they are synthesized within an original approach. The here proposed formalism allows to understand better both the spuriousing and the aliasing phenomena, as well as to accurately predict the impact of the latter on the data to be transmitted in terms of signal degradation. Second part of the paper provides an illustration and a validation of these theoretical developments via a direct application to a typical aerodynamic noise problem (aeroacoustic emission by a 2Dcylinder cross flow). There, it is further shown how the here proposed formalism can help in improving aeroacoustics hybrid calculations by predicting (and thus possibly minimizing) the bias to be induced on the acoustic extrapolation stage because of the aliasing and/or spuriousing effects inherited from the sampling rate reduction and/or interpolation of CFD data—which is likely to occur in any hybrid scenario. Copyright © 2012 John Wiley & Sons, Ltd.
Geotechnical design and construction issues for Lines 1 and 6 of the Naples Underground / Geotechnische Planung und Ausführung der U‐Bahnlinien 1 und 6 in Neapel
Authors: Russo Gianpiero , Viggiani Carlo , Viggiani G.M.B.
Published: June 2012

Since 1839, when the historical railway Naples – Portici was inaugurated, Naples has been characterized by a significant system of urban and suburban railways. The idea of a fully integrated urban rail network dates back to the 1950s, but construction only began in the 1990s. At present, the system includes 54 km of tracks and 69 stations in operation; ten lines with 93 km of track and a further 30 km of new light rail linking 114 stations with 21 interchanges are planned with the completion of the City Transport Plan.

The present paper reports on some geotechnical aspects of the design and construction of Lines 1 and 6, which are presently underway, discussing how the experience gathered during construction of Line 1 influenced some of the design choices for Line 6.

Seit 1839, als die historische Eisenbahnstrecke Neapel – Portici eröffnet wurde, wurde Neapel durch sein umfangreiches Schienennetz im städtischen und vorstädtischen Bereich bekannt. Die Idee eines vollständig integrierten Bahnnetzes geht in die 1950er Jahre zurück, der Bau wurde jedoch erst in den 1990er Jahren aufgenommen. Derzeit umfasst das Netz 54 km Schiene und 69 Stationen; mit Vollendung des städtischen Verkehrsplans sind zehn Linien mit 93 km Schiene sowie weitere 30 km einer neuen Stadtbahn, die 114 Stationen und 21 Knotenpunkte verbindet, geplant.

Dieser Artikel beschreibt einige geotechnische Aspekte hinsichtlich Planung und Ausführung der sich derzeit im Bau befindlichen Linien 1 und 6, wobei erläutert wird, wie die beim Bau der Linie 1 gesammelten Erfahrungswerte einige Planungsentscheidungen der Linie 6 beeinflusst haben.
Design and construction aspects of Milan underground Line 5 – passing over the Bovisa‐Dateo railway tunnel / Planungs‐ und Ausführungsaspekte der Mailänder U‐Bahnlinie 5 – Überquerung des Bovisa‐Dateo Bahntunnels
Authors: Fava Adriano , Galvanin Paolo , Socci Andrea , De Sanctis Fiorenze , Gamba Francesco
Published: June 2012

The design and construction aspects related to Line 5 of the Milan Underground are presented with attention to the section of the tunnel passing the city Railway Link between Bovisa and Dateo stations. Numerical modelling was used to design the soil improvement systems around the excavation and under the buildings, and also to establish threshold values of the parameters to be monitored. At the same time, a monitoring system was implemented in order to verify the design predictions during construction and to allow, whenever necessary, the adoption of the corrective actions planned during the design stage. Following a brief description of the work, the fundamental design steps are described in conjunction with the problems that had to be solved, the technical solutions proposed and the approach adopted during construction.

In diesem Artikel werden die Planungs‐ und Ausführungsaspekte der Linie 5 des Mailänder U‐Bahnsystems vorgestellt. Besonderes Augenmerk liegt auf dem Abschnitt des Tunnels, der die städtische Bahnverbindung zwischen den Stationen Bovisa und Dateo passiert. Numerische Modellierungen wurden durchgeführt, um die Bodenverbesserungsmaßnahmen rund um die Baugruben und unter den Gebäuden zu planen, und um Grenzwerte für die zu beobachteten Parameter festzulegen. Gleichzeitig wurde ein Monitoringsystem eingeführt, das es ermöglichte, die zuvor gemachten Planungsvorhersagen während der Ausführung zu überprüfen und, wenn nötig, während der Planungsphase entworfene korrigierende Maßnahmen durchzuführen. Nach einer kurzen Beschreibung der Arbeiten werden die grundlegenden Planungsschritte vorgestellt sowie die Probleme, die während dieser Phase gelöst werden mussten. Auch die technischen Lösungen, die vorgeschlagen und während der Bauphase ausgeführt wurden, werden diskutiert.
Absolute monocytosis at diagnosis correlates with survival in diffuse large B‐cell lymphoma—possible link with monocytic myeloid‐derived suppressor cells
Authors: Tadmor Tamar , Fell Rona , Polliack Aaron , Attias Dina
Published: June 2012

Some patients with lymphoma have monocytosis at diagnosis, but its significance is unclear. The recently recognized subpopulation, monocytic myeloid‐derived suppressor cells (M‐MDSCs), has immunoregulatory function, suppresses host anti‐tumour immunity and plays a role in cancer tolerance. Data from 91 untreated patients with diffuse large B‐cell lymphoma (DLBCL) were evaluated for monocytosis >1000/mm3 at diagnosis and its significance compared with a number of well‐established prognostic factors for DLBCL including age, stage, gender, B symptoms, extranodal sites, LDH and CRP levels, bone marrow involvement and International Prognostic Index (IPI) score. In 23 of these patients with DLBCL and 15 healthy controls, the proportion of M‐MDSCs in the peripheral blood was determined by flow cytometry. Monocytosis was found in 17.6% of the patient cohort examined. In the multivariate analysis, bone marrow involvement, IPI score and monocytosis were the only independent prognostic factors seen to be associated with decreased progression free and overall survival. Patients with DLBCL had on average increased M‐MDSCs counts at diagnosis compared with controls, which returned to normal after achieving remission. In conclusion, monocytosis was identified as an independent prognostic factor in DLBCL and correlated with worse overall survival. The significant increases in the M‐MDSCs pool observed in some of the cases examined may possibly help to explain why monocytosis is associated with poor outcome in these patients. Copyright © 2012 John Wiley & Sons, Ltd.
The effects of free government health insurance among small children—evidence from the free care for children under six policy in Vietnam
Authors: Nguyen Ha , Wang Wenjuan
Published: June 2012

Over the last few years, there have been an increasing number of impact evaluations of health insurance and other demand‐side financing programs in developing countries. Yet the literature on insurance impact among small children is limited. This paper evaluates the effects of a Vietnamese government's policy in 2005, which granted free access to health services in public facilities to all children younger than 6 years. In particular, we focus on children among households who are not eligible for a program for the poor, which has been administered concurrently in the country. Using two waves of the Vietnam Household Living Standard Surveys conducted right before and after the policy started and a difference‐in‐differences method, we found a major increase in both inpatient and outpatient care in the secondary public hospitals. At the same time, there is evidence indicating a reduction in the use of tertiary hospitals. Compared with the policy's non‐beneficiaries, beneficiaries in the age group 4–5 years also experienced fewer sick days, incurred less out‐of‐pocket spending on healthcare, and were less likely to encounter catastrophic expenditure. Evidence thus suggests that insurance provided by the policy has served the function as a safety net and helped improving efficiency of the health system by reducing the use of costly tertiary care. Copyright © 2012 John Wiley & Sons, Ltd.
CONDITIONALLY HETEROSKEDASTIC FACTOR MODELS WITH SKEWNESS AND LEVERAGE EFFECTS
Authors: Dovonon Prosper
Published: June 2012

Conditional heteroskedasticity, skewness and leverage effects are well‐known features of financial returns. The literature on factor models has often made assumptions that preclude the three effects to occur simultaneously. In this paper I propose a conditionally heteroskedastic factor model that takes into account the presence of both the conditional skewness and leverage effects. This model is specified in terms of conditional moment restrictions and unconditional moment conditions are proposed allowing inference by the generalized method of moments (GMM). The model is also shown to be closed under temporal aggregation. An application to daily excess returns on sectorial indices from the UK stock market provides strong evidence for dynamic conditional skewness and leverage with a sharp efficiency gain resulting from accounting for both effects. The estimated volatilitypersistence from the proposed model is lower than that estimated from models that rule out such effects. I also find that the longer the returns' horizon, the fewer conditionally heteroskedastic factors may be required for suitable modeling and the less strong is the evidence for dynamic leverage. Some of these results are in line with the main findings of Harvey and Siddique () and Jondeau and Rockinger (), namely that accounting for conditional skewness impacts the persistence in the conditional variance of the return process. Copyright © 2012 John Wiley & Sons, Ltd.
Parallel‐ProBiS: Fast parallel algorithm for local structural comparison of protein structures and binding sites
Authors: Konc Janez , Depolli Matjaž , Trobec Roman , Rozman Kati , Janežič Dušanka
Published: June 2012

The ProBiS algorithm performs a local structural comparison of the query protein surface against the nonredundant database of protein structures. It finds proteins that have binding sites in common with the query protein. Here, we present a new parallelized algorithm, Parallel‐ProBiS, for detecting similar binding sites on clusters of computers. The obtained speedups of the parallel ProBiS scale almost ideally with the number of computing cores up to about 64 computing cores. Scaling is better for larger than for smaller query proteins. For a protein with almost 600 amino acids, the maximum speedup of 180 was achieved on two interconnected clusters with 248 computing cores. Source code of Parallel‐ProBiS is available for download free for academic users at http://probis.cmm.ki.si/download. © 2012 Wiley Periodicals, Inc.
Suppression of GLUT1; A new strategy to prevent diabetic complications
Authors: Lu Lili , Seidel Christopher P. , Iwase Takeshi , Stevens Rebecca K. , Gong Yuan‐Yuan , Wang Xinyi , Hackett Sean F. , Campochiaro Peter A.
Published: June 2012

High blood glucose results in high glucose levels in retina, because GLUT1, the sole glucose transporter between blood and retina, transports more glucose when blood glucose is high. This is the ultimate cause of diabetic retinopathy. Knockdown of GLUT1 by intraocular injections of a pool of siRNAs directed against SLC2A1 mRNA which codes for GLUT1 significantly reduced mean retinal glucose levels in diabetic mice. Systemic treatment of diabetic mice with forskolin or genistein, which bind GLUT1 and inhibit glucose transport, significantly reduced retinal glucose to the same levels seen in non‐diabetics. 1,9‐Dideoxyforskolin, which binds GLUT1 but does not stimulate adenylate cyclase had an equivalent effect to that of forskolin regarding lowering retinal glucose in diabetics indicating that cyclic AMP is noncontributory. GLUT1 inhibitors also reduced glucose and glycohemoglobin levels in red blood cells providing a peripheral biomarker for the effect. In contrast, brain glucose levels were not increased in diabetics and not reduced by forskolin. Treatment of diabetics with forskolin prevented early biomarkers of diabetic retinopathy, including elevation of superoxide radicals, increased expression of the chaperone protein β2 crystallin, and increased expression of vascular endothelial growth factor (VEGF). These data identify GLUT1 as a promising therapeutic target for prevention of diabetic retinopathy. J. Cell. Physiol. 228: 251–257, 2013. © 2012 Wiley Periodicals, Inc.
Rules of engagement for base excision repair in chromatin
Authors: Odell Ian D. , Wallace Susan S. , Pederson David S.
Published: June 2012

Most of the DNA in eukaryotes is packaged in tandemly arrayed nucleosomes that, together with numerous DNA‐ and nucleosome‐associated enzymes and regulatory factors, make up chromatin. Chromatin modifying and remodeling agents help regulate access to selected DNA segments in chromatin, thereby facilitating transcription and DNA replication and repair. Studies of nucleotide excision repair (NER), single strand break repair (SSBR), and the homology‐directed repair (HDR), and non‐homologous end‐joining (NHEJ) double strand break repair pathways have led to an “access‐repair‐restore” paradigm, in which chromatin in the vicinity of damaged DNA is disrupted, thereby enabling efficient repair and the subsequent repackaging of DNA into nucleosomes. When damage is extensive, these repair processes are accompanied by cell cycle checkpoint activation, which provides cells with sufficient time to either complete the repair or initiate apoptosis. It is not clear, however, if base excision repair (BER) of the ∼20,000 or more oxidative DNA damages that occur daily in each nucleated human cell can be viewed through this same lens. Until recently, we did not know if BER requires or is accompanied by nucleosome disruption, and it is not yet clear that anything short of overwhelming oxidative damage (resulting in the shunting of DNA substrates into other repair pathways) results in checkpoint activation. This review highlights studies of how oxidatively damaged DNA in nucleosomes is discovered and repaired, and offers a working model of events associated with BER in chromatin that we hope will have heuristic value. J. Cell. Physiol. 228: 258–266, 2013. © 2012 Wiley Periodicals, Inc.
Understanding the targeting of the RB family proteins by viral oncoproteins to defeat their oncogenic machinery
Authors: Bellacchio Emanuele , Paggi Marco G.
Published: June 2012

The retinoblastoma (RB) family consists of three genes, RB1, RBL1, and RBL2, that code for the pRb, p107, and pRb2/p130 proteins, respectively. All these factors have pivotal roles in controlling fundamental cellular mechanisms such as cell cycle, differentiation and apoptosis. The founder and the most investigated RB family protein is pRb, which is considered to be the paradigm of tumor suppressors. However, p107 and pRb2/p130 clearly display a high degree of structural and functional homology with pRb. Interestingly, these factors were first identified as physical targets of the Adenovirus E1A oncoprotein. Indeed, RB family proteins are the most important and widely investigated targets of small DNA virus oncoproteins, such as Adenovirus E1A, human papillomavirus E7 and Simian virus 40 large T antigen. By interacting with pRb and with other RB family members, these oncoproteins neutralize their growth suppressive properties, thus stimulating proliferation of the infected cells, de‐differentiation, and resistance to apoptosis. All these acquired features strongly favor the rise and selection of immortalized and mutation‐prone cells, leading to a higher propensity in undergoing transformation. Our present work aims to illustrate and delve into these protein–protein interactions. Considering that these viral oncoproteins are dispensable for normal cellular functions, they can create “oncogene addiction” in the infected/transformed cells. This makes the possibility to dismantle these interactions extremely attractive, thus promoting the development of highly specific smart molecules capable of targeting only the infected/transformed cells that express these viral factors. J. Cell. Physiol. 228: 285–291, 2013. © 2012 Wiley Periodicals, Inc.
Augmented LPS responsiveness in type 1 diabetes‐derived osteoclasts
Authors: Catalfamo Dana L. , Calderon Nadia L. , Harden Scott W. , Sorenson Heather L. , Neiva Kathleen G. , Wallet Shannon M.
Published: June 2012

Bone abnormalities are frequent co‐morbidities of type 1 diabetes (T1D) and are principally mediated by osteoblasts and osteoclasts which in turn are regulated by immunologic mediators. While decreased skeletal health in T1D involves alterations in osteoblast maturation and function, the effect of altered immune function on osteoclasts in T1D‐associated bone and joint pathologies is less understood. Here T1D‐associated osteoclast‐specific differentiation and function in the presence and absence of inflammatory mediators was characterized utilizing bone marrow‐derived osteoclasts (BM‐OCs) isolated from non‐obese diabetic (NOD) mice, a model for spontaneous autoimmune diabetes with pathology similar to individuals with T1D. Differentiation and osteoclast‐mediated bone resorption were evaluated along with cathepsin K, MMP‐9, and immune soluble mediator expression. The effect of lipopolysaccharide (LPS), a pro‐inflammatory cytokine cocktail, and NOD‐derived conditioned supernatants on BM‐OC function was also determined. Although NOD BM‐OCs cultures contained smaller osteoclasts, they resorbed more bone concomitant with increased cathepsin K, MMP‐9, and pro‐osteoclastogenic mediator expression. NOD BM‐OCs also displayed an inhibition of LPS‐induced deactivation that was not a result of soluble mediators produced by NOD BM‐OCs, although a pro‐inflammatory milieu did enhance NOD BM‐OCs bone resorption. Together these data indicate that osteoclasts from a T1D mouse model hyper‐respond to RANK‐L resulting in excessive bone degradation via enhanced cathepsin K and MMP‐9 secretion concomitant with an increased expression of pro‐osteoclastic soluble mediators. Our data also suggest that inhibition of LPS‐induced deactivation in NOD‐derived BM‐OC cultures is most likely due to NOD osteoclast responsiveness rather than LPS‐induced expression of soluble mediators. J. Cell. Physiol. 228: 349–361, 2013. © 2012 Wiley Periodicals, Inc.
On the role of retinoblastoma family proteins in the establishment and maintenance of the epigenetic landscape
Authors: Fiorentino Francesco Paolo , Marchesi Irene , Giordano Antonio
Published: June 2012

RB family members are negative regulators of the cell cycle, involved in numerous biological processes such as cellular senescence, development and differentiation. Disruption of RB family pathways are linked to loss of cell cycle control, cellular immortalization and cancer. RB family, and in particular the most studied member RB/p105, has been considered a tumor suppressor gene by more than three decades, and numerous efforts have been done to understand his molecular activity. However, the epigenetic mechanisms behind Rb‐mediated tumor suppression have been uncovered only in recent years. In this review, the role of RB family members in cancer epigenetics will be discussed. We start with an introduction to epigenomes, chromatin modifications and cancer epigenetics. In order to provide a clear picture of the involvement of RB family in the epigenetic field, we describe the RB family role in the epigenetic landscape dynamics based on the heterochromatin variety involved, facultative or constitutive. We want to stress that, despite dissimilar modulations, RB family is involved in both mammalian varieties of heterochromatin establishment and maintenance and that disruption of RB family pathways drives to alterations of both heterochromatin structures, thus to the global epigenetic landscape. J. Cell. Physiol. 228: 276–284, 2013. © 2012 Wiley Periodicals, Inc.
Retinoic acid protects cardiomyocytes from high glucose‐induced apoptosis through inhibition of NF‐κB signaling Pathway
Authors: Nizamutdinova Irina T. , Guleria Rakeshwar S. , Singh Amar B. , Kendall Jonathan A. , Baker Kenneth M. , Pan Jing
Published: June 2012

We have previously shown that retinoic acid (RA) has protective effects on high glucose (HG)‐induced cardiomyocyte apoptosis. To further elucidate the molecular mechanisms of RA effects, we determined the interaction between nuclear factor (NF)‐κB and RA signaling. HG induced a sustained phosphorylation of IKK/IκBα and transcriptional activation of NF‐κB in cardiomyocytes. Activated NF‐κB signaling has an important role in HG‐induced cardiomyocyte apoptosis and gene expression of interleukin‐6 (IL‐6), tumor necrosis factor (TNF)‐α, and monocyte chemoattractant protein‐1 (MCP‐1). All‐trans RA (ATRA) and LGD1069, through activation of RAR/RXR‐mediated signaling, inhibited the HG‐mediated effects in cardiomyocytes. The inhibitory effect of RA on NF‐κB activation was mediated through inhibition of IKK/IκBα phosphorylation. ATRA and LGD1069 treatment promoted protein phosphatase 2A (PP2A) activity, which was significantly suppressed by HG stimulation. The RA effects on IKK and IκBα were blocked by okadaic acid or silencing the expression of PP2Ac‐subunit, indicating that the inhibitory effect of RA on NF‐κB is regulated through activation of PP2A and subsequent dephosphorylation of IKK/IκBα. Moreover, ATRA and LGD1069 reversed the decreased PP2A activity and inhibited the activation of IKK/IκBα and gene expression of MCP‐1, IL‐6, and TNF‐α in the hearts of Zucker diabetic fatty rats. In summary, our findings suggest that the suppressed activation of PP2A contributed to sustained activation of NF‐κB in HG‐stimulated cardiomyocytes; and that the protective effect of RA on hyperglycemia‐induced cardiomyocyte apoptosis and inflammatory responses is partially regulated through activation of PP2A and suppression of NF‐κB‐mediated signaling and downstream targets. J. Cell. Physiol. 228: 380–392, 2013. © 2012 Wiley Periodicals, Inc.
Decolorization of textile dyes by Bjerkandera sp. BOL 13 using waste biomass as carbon source
Authors: Jonstrup Maria , Kumar Naresh , Guieysse Benoit , Murto Marika , Mattiasson Bo
Published: June 2012

BACKGROUND: Phanerochaete chrysosporium, Trametes versicolor and Bjerkandera sp BOL13 were compared for decolorization of azo dyes supplied individually or as a mixture. The dye decolorization was also evaluated during continuous treatment under non‐sterile conditions using a lignocellulosic growth substrate.

RESULTS: Bjerkandera sp BOL13 showed the highest dye decolorization potential. This fungus was also found to support high decolorization of Remazol Red RR at an initial pH of 4‐6 and when using straw as co‐substrate. The fungus was evaluated for Remazol Red RR decolorization in a continuously fed packed‐bed bioreactor operated under non‐sterile conditions with 3 days of hydraulic retention time. When glucose was supplied as growth‐substrate, decolorization efficiencies of 65‐90% were maintained for 12 days in a bioreactor packed with wooden material. The decolorization efficiency was lower when glucose was not fed to the fungus or when a plastic material was used as packing. Higher manganese peroxidase and laccase activities were also recorded when the wood packing was used. Contamination caused a drop in decolorization efficiency after 17‐19 days operation.

CONCLUSIONS: The potential of Bjerkandera sp BOL13 for decolorization of azo dyes under non‐sterile conditions using lignocellulosic growth substrates was demonstrated. Research is needed to reduce contamination under non‐sterile conditions. © 2012 Society of Chemical Industry
Methodology for advanced measurement accuracy of the overall volumetric oxygen transfer coefficient with application to hydrocarbon–aqueous dispersions
Authors: Clarke Kim G , Manyuchi Musaida M
Published: June 2012

Accurate quantification of the overall volumetric oxygen transfer coefficient (KLa) is essential for the success of aerobic bioprocesses. In hydrocarbon‐based bioprocesses where KLa is depressed at higher viscosities, this is particularly critical. In this study an accessible methodology for KLa determination has been developed and validated for alkane‐based systems under a wide range of process conditions. Critical to measurement accuracy in around 90% of the KLa values was the incorporation of the response lag. Neglect of the response lag resulted in errors greater than 5% above KLa = 0.3Kp to KLa = 0.6Kp (where Kp is the inverse response lag or probe constant), at least 1.5‐fold to 3‐fold lower than the analogous KLa in water. Further, Kp varied significantly with both alkane concentration and chain length. A sensitivity analysis confirmed − 25% to 90% error in KLa with 30% over‐ and under‐estimation of Kp respectively. When incorporating Kp values specific to the process conditions, accurate KLa values were confirmed in 0 to 20% (v/v) C10–13 and C14–20 aqueous dispersions over 600 to 1200 rpm agitation. Copyright © 2012 Society of Chemical Industry
Novel two‐in‐one bioreactor greatly improves lactic acid production from xylose by Lactobacillus pentosus
Authors: Puah Sze Min , Huynh Han Vinh , Wu Jin Chuan
Published: June 2012

BACKGROUND: Simultaneous xylose isomerization and fermentation was investigated to improve the lactic acid production from xylose by Lactobacillus pentosus in a novel two‐in‐one bioreactor constructed by packing the immobilized xylose isomerase (65 g) in a fixed bed reactor (diameter 56 mm × 66 mm, packing volume 154 mL) with a permeable wall, which was installed inside a conventional fermenter (2 L) and rotated along the axis together with the mechanical stirrer of the fermenter.

RESULTS: Xylose (20 g L−1) was completely consumed within 24 h in the novel bioreactor, compared with 72 h needed for the control without packed enzyme. The maximum cell density (17.5 g L−1) in the novel bioreactor was twice that in the control and the lactic acid productivity (0.58 g L−1 h−1) was 3.8 times higher. Repeated use of the immobilized enzyme showed that the lactic acid productivity and yield obviously dropped after the first batch fermentation but maintained almost unchanged afterwards.

CONCLUSION: Simultaneous xylose isomerization and fermentation significantly improved lactic acid production from xylose by Lactobacillus pentosus. The novel bioreactor made it easier to recycle and reuse the immobilized enzyme. © 2012 Society of Chemical Industry
A Cartesian non‐uniform grid interpolation method for fast field evaluation on elongated domains
Authors: Costa Nadav , Boag Amir
Published: June 2012

An algorithm for performing a fast evaluation on time harmonic fields radiated by two‐dimensional source constellations with elongated geometry is introduced. The suggested scheme attains a linear computational complexity. At the core of the algorithm is the idea of phase and amplitude compensation facilitating the conversion of fields radiated by spatially confined sources into bandlimited functions of the suitable coordinates. Thus, the fields or potentials are represented by their samples on sparse left‐side and right‐side non‐uniform Cartesian grids. These grids are employed both for the representation of outgoing fields and as targets for accumulating the incoming fields. Integrating this approach with the divide‐and‐conquer strategy, the algorithm relies on a binary hierarchical decomposition of the computational domain. The total field is computed via a two‐way multilevel process, which passes through all of the left‐side and right‐side grids, while systematically aggregating all subdomains' contributions, ending with the field interpolation back to the desired observation points. Copyright © 2012 John Wiley & Sons, Ltd.
Transcriptional profiling of microdissected areas of active multiple sclerosis lesions reveals activation of heat shock protein genes
Authors: Mycko Marcin P. , Brosnan Celia F. , Raine Cedric S. , Fendler Wojciech , Selmaj Krzysztof W.
Published: June 2012

Heat shock proteins (HSPs) are stress‐responsive proteins that serve as important molecules contributing to cellular “protein triage.” We and others have reported an increase of selected HSPs in multiple sclerosis (MS) lesions. However, the exact expression pattern of HSP family genes in MS is not known. The aim of our research was to assess global transcriptional changes of all gene members of the HSP families within MS lesions and associated normal‐appearing white matter (NAWM). To this end, we used laser capture microdissection (LCM) to isolate defined regions of chronic–active MS lesions (n = 5), one of the most common types of MS lesions. To identify changes in HSP genes in relation to different areas of the plaque, we used genome‐wide microarray analysis. We detected a significant change in the transcriptional profile of the demyelinated region compared with NAWM. In particular, overall expression of different HSP genes was upregulated in different areas of chronic–active lesion. These changes were linked to an upregulation of heat shock factor 4 (HSF4). This is the first global analysis of transcriptional changes in HSPs in the central nervous system during MS. The results support a relationship between HSP activation and lesion activity. © 2012 Wiley Periodicals, Inc.
Dopaminergic modulation of low‐Mg2+‐induced epileptiform activity in the intact hippocampus of the newborn mouse in vitro
Authors: Sharopov Salim , Moser Jochen , Chen Rongqing , Kolbaev Sergey N. , Bernedo Viviane E. , Werhahn Konrad J. , Luhmann Heiko J. , Kilb Werner
Published: June 2012

To investigate whether epileptiform activity in the immature brain is modulated by dopamine, we examined the effects of dopaminergic agonists and antagonists in an intact in vitro preparation of the isolated corticohippocampal formation of immature (postnatal days 3 and 4) C57/Bl6 mice using field potential recordings from CA3. Epileptiform discharges were induced by a reduction of the extracellular Mg2+ concentration to 0.2 mM. These experiments revealed that low concentrations of dopamine (<0.3 μM) attenuated epileptiform activity, whereas >3 μM dopamine enhanced epileptiform activity. The D1‐agonist SKF38393 (10 μM) had a strong proconvulsive effect, and the D2‐like agonist quinpirole (10 μM) mediated a weak anticonvulsive effect. The proconvulsive effect of 10 μM dopamine was completely abolished by the D1‐like receptor antagonist SCH39166 (2 μM) or the D2‐like antagonist sulpiride (10 μM), whereas the D2 antagonist L‐741626 (50 nM) and the D3 antagonist SB‐277011‐A (0.1 μM) were without effect. The anticonvulsive effect of 0.1 μM dopamine could be suppressed by D1‐like, D2, or D3 receptor antagonists. A proconvulsive effect of 10 μM dopamine was also observed when AMPA, NMDA, or GABAA receptors were blocked. In summary, these results suggest that 1) dopamine influences epileptiform activity already at early developmental stages; 2) dopamine can bidirectionally influence the excitability; 3) D1‐like receptors mediate the proconvulsive effect of high dopamine concentrations, although the pharmacology of the anticonvulsive effect is less clear; and 4) dopamine‐induced alterations in GABAergic and glutamatergic systems may contribute to this effect. © 2012 Wiley Periodicals, Inc.
Transgenic mice expressing yellow fluorescent protein under control of the human tyrosine hydroxylase promoter
Authors: Choi Eun Yang , Yang Jae Won , Park Myung Sun , Sun Woong , Kim Hyun , Kim Seung U. , Lee Myung Ae
Published: June 2012

Pathogenesis of Parkinson's disease and related catecholaminergic neurological disorders is closely associated with changes in the levels of tyrosine hydroxylase (TH). Therefore, investigation of the regulation of the TH gene system should assist in understanding the pathomechanisms involved in these neurological disorders. To identify regulatory domains that direct human TH expression in the central nervous system (CNS), we generated two transgenic mouse lines in which enhanced yellow fluorescent protein (EYFP) is expressed under the control of either 3.2‐kb (hTHP‐EYFP construct) human TH promoter or 3.2‐kb promoter with 2‐kb 3′‐flanking regions (hTHP‐ex3‐EYFP construct) of the TH gene. In the adult transgenic mouse brain, the hTHP‐EYFP construct directs neuron‐specific EYFP expression in various CNS areas, such as olfactory bulb, striatum, interpeduncular nucleus, cerebral cortex, hippocampus, and particularly dentate gyrus. Although these EYFP‐positive cells were identified as mature neurons, few EYFP‐positive cells were TH‐positive neurons. On the other hand, we could detect the EYFP mRNA expression in a subset of neurons in the olfactory bulb, midbrain, and cerebellum, in which expression of endogenous TH is enriched, with hTHP‐ex3‐EYFP transgenic mice. These results indicate that the 3.2‐kb sequence upstream of the TH gene is not sufficient for proper expression and that the 2‐kb sequence from the translation start site to exon 3 is necessary for expression of EYFP in a subset of catecholaminergic neurons. © 2012 Wiley Periodicals, Inc.
S‐52, a novel nootropic compound, protects against β‐amyloid induced neuronal injury by attenuating mitochondrial dysfunction
Authors: Gao Xin , Zheng Chun Yan , Qin Guo Wei , Tang Xi Can , Zhang Hai Yan
Published: June 2012

Accumulating evidence suggests that β‐amyloid (Aβ)‐induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S‐52, a novel nootropic compound, on Aβ‐induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S‐52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S‐52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ‐harmed cells but also in unharmed, normal cells. The role of S‐52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S‐52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy. © 2012 Wiley Periodicals, Inc.
Effects of vascular endothelial growth factor in ischemic stroke
Authors: Ma Yihui , Zechariah Anil , Qu Yan , Hermann Dirk M.
Published: June 2012

Vascular endothelial growth factor (VEGF) is a pleiotropic growth factor that is crucially involved in neurovascular remodeling in the ischemic brain. VEGF promotes angiogenesis, protects ischemic neurons from injury, has potent anti‐inflammatory actions, and promotes brain plasticity, in addition to enhancing the recruitment and proliferation of neural precursor cells. These broad actions make VEGF interesting as a model molecule that allows understanding endogenous responses of the brain to injuries. However, several studies indicate that the route and timing of VEGF administration are crucial for the effects of VEGF on ischemic brain tissue. Hence, systemic VEGF delivery in the very acute stroke phase may exacerbate brain damage because of the promotion of blood–brain barrier breakdown that inevitably accompanies vascular growth. Future studies aimed at the promotion of neurovascular remodeling in ischemic stroke should carefully take into consideration pleiotropic actions of angiogenic growth factors beyond vascular growth. © 2012 Wiley Periodicals, Inc.
Magnesium sulfate treatment decreases the initial brain damage alterations produced after perinatal asphyxia in fetal lambs
Authors: Goñi‐de‐Cerio Felipe , Alvarez Antonia , Lara‐Celador Idoia , Alvarez Francisco J. , Alonso‐Alconada Daniel , Hilario Enrique
Published: June 2012

The aim of this work was to analyze the effect of MgSO4 treatment in the brain after hypoxic–ischemic (HI) injury in premature fetal lambs. Injury was induced by partial occlusion of umbilical cord for 60 min, and then the preterm lambs (80–90% of gestation) were randomly assigned to one of the following groups: control group, in which the animals were managed by conventional mechanical ventilation for 3 hr; 3 hr postpartial cord occlusion (3‐hr‐PCO) group, in which injured animals were managed by ventilation and then sacrificed 3 hr after HI; and MgSO4 group, in which animals received 400 mg/kg MgSO4 for 20 min soon after HI was induced and were managed by ventilation for 3 hr. Brains were analyzed for apoptosis by TUNEL assay. Cell viability and intracellular state studies were assessed by flow cytometry. The delayed death index was significantly increased in the 3‐hr‐PCO group in comparison with control. Administration of MgSO4 elicited a delay in cell death that was similar to that in the control group. The 3‐hr‐PCO group showed a significantly higher concentration of reactive oxygen species, mitochondrial damage, and intracellular calcium in comparison with control and MgSO4‐ treated groups. Our results suggest that MgSO4 treatment might have potential therapeutic benefits after the HI event. © 2012 Wiley Periodicals, Inc.
Trauma‐specific insults to the cochlear nucleus in the rat
Authors: Sekiya Tetsuji , Viberg Agneta , Kojima Ken , Sakamoto Tatsunori , Nakagawa Takayuki , Ito Juichi , Canlon Barbara
Published: June 2012

The effect of acoustic overstimulation on the neuronal number of the cochlear nucleus (CN) was investigated by using unbiased stereological methods in rats. We found that, after 9 weeks of recovery, neurons in the anteroventral cochlear nucleus (AVCN) degenerated, whereas those in the posteroventral and dorsal cochlear nuclei (PVCN and DCN) were preserved. The noise trauma induced near complete loss of the outer hair cells throughout the cochlea, and the inner hair cells were preserved only in the more apical regions. This pattern of selective loss of AVCN neurons in this study was different from trauma induced by auditory deafferentation by mechanical compression of auditory neurons. In contrast to noise trauma, mechanical compression caused loss of neurons in the PVCN and DCN. After 5 weeks of recovery from mechanical compression, there was no loss of inner or outer hair cells. These findings indicate that auditory deprivation, induced by different experimental manipulations, can have strikingly different consequences for the central auditory system. We hypothesized that AVCN neuronal death was induced by excitotoxic mechanisms via AMPA‐type glutamate receptors and that excitatory neuronal circuits developed after acoustic overstimulation protected the PVCN and DCN against neuronal death. The results of the present study demonstrate that hearing loss from different etiologies will cause different patterns of neuronal degeneration in the CN. These findings are important for enhancing the performance of cochlear implants and auditory brainstem implants, because diverse types of hearing loss can selectively affect neuronal degeneration of the CN. © 2012 Wiley Periodicals, Inc.
Cardiovascular responses to glutamate microinjection in the dorsomedial periaqueductal gray of unanesthetized rats
Authors: Pelosi Gislaine Garcia , Busnardo Cristiane , Tavares Rodrigo Fiacadori , Corrêa Fernando Morgan Aguiar
Published: June 2012

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation. Glutamate (L‐Glu) is an abundant excitatory amino acid in the central nervous system (CNS) and is present in the rat PAG. Moreover, data in the literature indicate its involvement in central blood pressure control. Here we report on the cardiovascular effects caused by microinjection of L‐Glu into the dorsomedial PAG (dmPAG) of rats and the glutamatergic receptors as well as the peripheral mechanism involved in their mediation. The microinjection of L‐Glu into the dmPAG of unanesthetized rats evoked dose‐related pressor and bradycardiac responses. The cardiovascular response was significantly reduced by pretreatment of the dmPAG with a glutamatergic M‐methyl‐D‐aspartate (NMDA) receptor antagonist (LY235959) and was not affected by pretreatment with a non‐NMDA receptor antagonist (NBQX), suggesting a mediation of that response by the activation of NMDA receptors. Furthermore, the pressor response was blocked by pretreatment with the ganglion blocker pentolinium (5 mg/kg, intravenously), suggesting an involvement of the sympathetic nervous system in this response. Our results indicate that the microinjection of L‐Glu into the dmPAG causes sympathetic‐mediated pressor responses in unanesthetized rats, which are mediated by glutamatergic NMDA receptors in the dmPAG. © 2012 Wiley Periodicals, Inc.
Amino acid concentrations in the hamster central auditory system and long‐term effects of intense tone exposure
Authors: Godfrey Donald A. , Kaltenbach James A. , Chen Kejian , Ilyas Omer , Liu Xiaochen , Licari Frank , Sacks Justin , McKnight Darwin
Published: June 2012

Exposure to intense sounds often leads to loss of hearing of environmental sounds and hearing of a monotonous tonal sound not actually present, a condition known as tinnitus. Chronic physiological effects of exposure to intense tones have been reported for animals and should be accompanied by chemical changes present at long times after the intense sound exposure. By using a microdissection mapping procedure combined with high‐performance liquid chromatography (HPLC), we have measured concentrations of nine amino acids, including those used as neurotransmitters, in the cochlear nucleus, inferior colliculus, medial geniculate, and auditory cortex of hamsters 5 months after exposure to an intense tone, compared with control hamsters of the same age. No very large differences in amino acid concentrations were found between exposed and control hamsters. However, increases of glutamate and γ‐aminobutyrate (GABA) in some parts of the inferior colliculus of exposed hamsters were statistically significant. The most consistent differences between exposed and control hamsters were higher aspartate and lower taurine concentrations in virtually all regions of exposed hamsters, which reached statistical significance in many cases. Although these amino acids are not considered likely neurotransmitters, they indirectly have roles in excitatory and inhibitory neurotransmission, respectively. Thus, there is evidence for small, widespread, long‐term increases in excitatory transmission and decreases in inhibitory transmission after a level of acoustic trauma previously shown to produce hearing loss and tinnitus. © 2012 Wiley Periodicals, Inc.
Osteoblast and osteocyte‐specific loss of Connexin43 results in delayed bone formation and healing during murine fracture healing
Authors: Loiselle Alayna E. , Paul Emmanuel M. , Lewis Gregory S. , Donahue Henry J.
Published: June 2012

Connexin43 (Cx43) plays an important role in osteoblastic differentiation in vitro, and bone formation in vivo. Mice with osteoblast/osteocyte‐specific loss of Cx43 display decreased gap junctional intercellular communication (GJIC), bone density, and cortical thickness. To determine the role of Cx43 in fracture healing, a closed femur fracture was induced in Osteocalcin‐Cre+; Cx43flox/flox (Cx43cKO) and Cre‐; Cx43flox/flox (WT) mice. We tested the hypothesis that loss of Cx43 results in decreased bone formation and impaired healing following fracture. Here, we show that osteoblast and osteocyte‐specific deletion of Cx43 results in decreased bone formation, bone remodeling, and mechanical properties during fracture healing. Cx43cKO mice display decreased bone volume, total volume, and fewer TRAP+ osteoclasts. Furthermore, loss of Cx43 in mature osteoblasts and osteocytes results in a significant decrease in torsional rigidity between 21 and 35 days post‐fracture, compared to WT mice. These studies identify a novel role for the gap junction protein Cx43 during fracture healing, suggesting that loss of Cx43 can result in both decreased bone formation and bone resorption. Therefore, enhancing Cx43 expression or GJIC may provide a novel means to enhance bone formation during fracture healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:147–154, 2012