bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of quinolinic acid on human astrocytes morphology and functions: implications in Alzheimer's disease
Authors: Ting Ka Ka , Brew Bruce J , Guillemin Gilles J
Published: December 2009

The excitotoxin quinolinic acid (QUIN) is synthesized through the kynurenine pathway (KP) by activated monocyte lineage cells. QUIN is likely to play a role in the pathogenesis of several major neuroinflammatory diseases including Alzheimer's disease (AD). The presence of reactive astrocytes, astrogliosis, increased oxidative stress and inflammatory cytokines are important pathological hallmarks of AD. We assessed the stimulatory effects of QUIN at low physiological to high excitotoxic concentrations in comparison with the cytokines commonly associated with AD including IFN-γ and TNF-α on primary human astrocytes. We found that QUIN induces IL-1β expression, a key mediator in AD pathogenesis, in human astrocytes. We also explored the effect of QUIN on astrocyte morphology and functions. At low concentrations, QUIN treatment induced concomitantly a marked increase in glial fibrillary acid protein levels and reduction in vimentin levels compared to controls; features consistent with astrogliosis. At pathophysiological concentrations QUIN induced a switch between structural protein expressions in a dose dependent manner, increasing VIM and concomitantly decreasing GFAP expression. Glutamine synthetase (GS) activity was used as a functional metabolic test for astrocytes. We found a significant dose-dependent reduction in GS activity following QUIN treatment. All together, this study showed that QUIN is an important factor for astroglial activation, dysregulation and cell death with potential relevance to AD and other neuroinflammatory diseases.
Molecular evolution of measles viruses circulated in Taiwan 1992-2008
Authors: Cheng Wen-Yueh , Lee Lili , Rota Paul A , Yang Dustin Chen-Fu
Published: December 2009

Genetic analyses of viral samples from 74 laboratory confirmed measles cases occurring in Taiwan during 1992-2008 identified six viral genotypes D3, D5, D9, G2, H1 and H2. The most frequently detected genotype, H1, was associated with outbreaks in 1994 and 2002, and was the likely indigenous genotype in 1992. In response to the outbreaks, two catch-up campaigns were launched and a routine second dose of measles, mumps, and rubella vaccine at entry to elementary school was introduced. The vaccination campaigns successfully reduced the number of measles cases in Taiwan, and many of the more recent cases can be traced to importations, primarily from other Asian countries. A number of measles genotypes which were associated with outbreaks in other Asian countries were detected among the more recent cases. The more recent genotype H1 viruses had sequences that were identical to those currently circulating in China or associated with international importation of virus.
Protocol for the Osteoporosis Choice trial. A pilot randomized trial of a decision aid in primary care practice
Authors: Pencille Laurie J , Campbell Megan E , Van Houten Holly K , Shah Nilay D , Mullan Rebecca J , Swiglo Brian A , Breslin Maggie , Kesman Rebecca L , Tulledge-Scheitel Sidna M , Jaeger Thomas M , Johnson Ruth E , Bartel Gregory A , Wermers Robert A , Melton L Joseph , Montori Victor M
Published: December 2009

Background

Bisphosphonates can reduce fracture risk in patients with osteoporosis, but many at-risk patients do not start or adhere to these medications. The aims of this study are to: (1) preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid (O

STEOPOROSIS CHOICE
) for postmenopausal women at risk for osteoporotic fractures; and (2) assess the feasibility and validity (i.e., absence of contamination) of patient-level randomization (vs. cluster randomization) in pilot trials of decision aid efficacy.

Methods/Design

This is a protocol for a parallel, 2-arm, randomized trial to compare an intervention group receiving O

STEOPOROSIS CHOICE
to a control group receiving usual primary care. Postmenopausal women with bone mineral density T-scores of <-1.0, not receiving bisphosphonate therapy, and receiving care at participating primary care practices in and around Rochester, Minnesota, USA will be eligible to participate in the trial. We will measure the effect of OSTEOPOROSIS CHOICE on five outcomes: (a) patient knowledge regarding osteoporosis risk factors and treatment; (b) quality of the decision-making process for both the patient and clinician; (c) patient and clinician acceptability and satisfaction with the decision aid; (d) rate of bisphosphonate use and adherence, and (e) trial processes (e.g., ability to recruit participants, collect patient outcomes). To capture these outcomes, we will use patient and clinician surveys following each visit and video recordings of the clinical encounters. These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients (i.e., contamination). Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months.

Discussion

This pilot trial will provide evidence of feasibility, validity of patient randomization, and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures. The results will inform the design of a larger trial that could provide more precise estimates of the efficacy of the decision aid.

Trial registration

Clinical Trials.gov Identifier: NCT00578981
In silico approaches to study mass and energy flows in microbial consortia: a syntrophic case study
Authors: Taffs Reed , Aston John E , Brileya Kristen , Jay Zackary , Klatt Christian G , McGlynn Shawn , Mallette Natasha , Montross Scott , Gerlach Robin , Inskeep William P , Ward David M , Carlson Ross P
Published: December 2009

Background

Three methods were developed for the application of stoichiometry-based network analysis approaches including elementary mode analysis to the study of mass and energy flows in microbial communities. Each has distinct advantages and disadvantages suitable for analyzing systems with different degrees of complexity and a priori knowledge. These approaches were tested and compared using data from the thermophilic, phototrophic mat communities from Octopus and Mushroom Springs in Yellowstone National Park (USA). The models were based on three distinct microbial guilds: oxygenic phototrophs, filamentous anoxygenic phototrophs, and sulfate-reducing bacteria. Two phases, day and night, were modeled to account for differences in the sources of mass and energy and the routes available for their exchange.

Results

The in silico models were used to explore fundamental questions in ecology including the prediction of and explanation for measured relative abundances of primary producers in the mat, theoretical tradeoffs between overall productivity and the generation of toxic by-products, and the relative robustness of various guild interactions.

Conclusion

The three modeling approaches represent a flexible toolbox for creating cellular metabolic networks to study microbial communities on scales ranging from cells to ecosystems. A comparison of the three methods highlights considerations for selecting the one most appropriate for a given microbial system. For instance, communities represented only by metagenomic data can be modeled using the pooled method which analyzes a community's total metabolic potential without attempting to partition enzymes to different organisms. Systems with extensive a priori information on microbial guilds can be represented using the compartmentalized technique, employing distinct control volumes to separate guild-appropriate enzymes and metabolites. If the complexity of a compartmentalized network creates an unacceptable computational burden, the nested analysis approach permits greater scalability at the cost of more user intervention through multiple rounds of pathway analysis.
Inhibition of trypsin expression in Lutzomyia longipalpis using RNAi enhances the survival of Leishmania
Authors: Sant'Anna Mauricio RV , Diaz-Albiter Hector , Mubaraki Murad , Dillon Rod J , Bates Paul A
Published: December 2009

Background

Leishmania parasites must overcome several barriers to achieve transmission by their sand fly vectors. One of the earliest threats is exposure to enzymes during blood meal digestion. Trypsin-like enzymes appear to be detrimental to parasite survival during the very early phase of development as amastigotes transform into promastigote stages. Here, we investigate whether parasites can affect trypsin secretion by the sand fly midgut epithelium and if inhibition of this process is of survival value to the parasites.

Results

Infections of Lutzomyia longipalpis with Leishmania mexicana were studied and these showed that infected sand flies produced less trypsin-like enzyme activity during blood meal digestion when compared to uninfected controls. RNA interference was used to inhibit trypsin 1 gene expression by micro-injection into the thorax, as trypsin 1 is the major blood meal induced trypsin activity in the sand fly midgut. Injection of specific double stranded RNA reduced trypsin 1 expression as assessed by RT-PCR and enzyme assays, and also led to increased numbers of parasites in comparison with mock-injected controls. Injection by itself was observed to have an inhibitory effect on the level of infection, possibly through stimulation of a wound repair or immune response by the sand fly.

Conclusion

Leishmania mexicana was shown to be able to modulate trypsin secretion by Lutzomyia longipalpis to its own advantage, and direct inhibition of trypsin gene expression led to increased parasite numbers in the midguts of infected flies. Successful application of RNA interference methodology to Leishmania-infected sand flies now opens up the use of this technique to study a wide range of sand fly genes and their role in the parasite-vector interaction.
Carotid body tumors: radioguided surgical approach
Authors: Martinelli Ombretta , Irace Luigi , Massa Rita , Savelli Sara , Giannoni Fabrizia , Gattuso Roberto , Gossetti Bruno , Benedetti-Valentini Fabrizio , Izzo Luciano
Published: December 2009

Background

Carotid body tumours (CBTs) are very rare lesions which should be treated as soon as possible even when benign since small tumour size permits easier removal and lower incidence of perioperative complications and recurrence. Malignant forms are rare and they can be identified by lymph node invasion and metastases in distant locations. The need of reliable and effective diagnostic modalities for both primary CBTs and its metastases or recurrence is evident.

The present study reviews our experience and attempt to define the role of colour coded ultrasound (CCU) and Somatostatin receptor scintigraphy (SRS) with Indium-111-DTPA-pentetretide (Octreoscan®) using both planar and single photon emission tomography (SPECT) technique in the diagnosis and follow-up of these uncommon lesions within a multidisciplinary approach.

Methods

From 1997 to 2008, 12 patients suffering from 16 CBTs (4 bilateral) were investigated by CCU and SRS-SPECT before and after surgery. All tumours were grouped according to Shamblin's classification in order to assess the technical difficulties and morbidity of surgical resection on the ground of their size and relationship with the carotid arteries. Intraoperative radiocaptation by Octreoscan®) was also carried out in all cases to evaluate the radicality of surgery. All perioperative scans were evaluated by the same nuclear medicine physician.

Results

Preoperatively CCU showed CBTs (four were not palpable) with a sensitivity of 100%. Radioisotope imaging identified the CBTs as chemodectomas in 15 cases while no radioisotopic uptake was detected in 1 vagus nerve neurinoma. No evidence of metastasis or multicentricity were seen by total body radioisotopic scans. Combined data from CCU and SRS-SPECT allowed to determine tumour size in order to select 7 larger tumours which were submitted to selective preoperative embolization.

Intraoperatively Octreoscan demonstrated microscopic tumour leftovers promptly removed in 1 case and an unresectable remnant at the base of the skull in another case.

During follow-up CCI and radioisotope scans showed no recurrence in 14 cases and a slightly enlargement of the intracranial residual as detected during surgery in 1 patient.

Conclusion

CCU may allow an early and noninvasive detection of CBTs and hence safer operations. The combined use of CCU and SRS-SPECT provide useful data to identify those tumours and to evaluate their extent and carotid arteries infiltration. Radioisotope imaging is a sensitive modality to detect metastases and lymph node involvement that are markers of CBT malignancy. After surgery CCU and SRS-SPECT can be accurate modalities for surveillance for an early detection of CBTs recurrence.
Comparison of linear discriminant analysis methods for the classification of cancer based on gene expression data
Authors: Huang Desheng , Quan Yu , He Miao , Zhou Baosen
Published: December 2009

Background

More studies based on gene expression data have been reported in great detail, however, one major challenge for the methodologists is the choice of classification methods. The main purpose of this research was to compare the performance of linear discriminant analysis (LDA) and its modification methods for the classification of cancer based on gene expression data.

Methods

The classification performance of linear discriminant analysis (LDA) and its modification methods was evaluated by applying these methods to six public cancer gene expression datasets. These methods included linear discriminant analysis (LDA), prediction analysis for microarrays (PAM), shrinkage centroid regularized discriminant analysis (SCRDA), shrinkage linear discriminant analysis (SLDA) and shrinkage diagonal discriminant analysis (SDDA). The procedures were performed by software R 2.80.

Results

PAM picked out fewer feature genes than other methods from most datasets except from Brain dataset. For the two methods of shrinkage discriminant analysis, SLDA selected more genes than SDDA from most datasets except from 2-class lung cancer dataset. When comparing SLDA with SCRDA, SLDA selected more genes than SCRDA from 2-class lung cancer, SRBCT and Brain dataset, the result was opposite for the rest datasets. The average test error of LDA modification methods was lower than LDA method.

Conclusions

The classification performance of LDA modification methods was superior to that of traditional LDA with respect to the average error and there was no significant difference between theses modification methods.
Comparative, double-blind, controlled study of intra-articular hyaluronic acid (Hyalubrix®) injections versus local anesthetic in osteoarthritis of the hip
Authors: Migliore Alberto , Massafra Umberto , Bizzi Emanuele , Vacca Francesca , Martin-Martin Severino , Granata Mauro , Alimonti Andrea , Tormenta Sandro
Published: December 2009

Introduction

Comparison of intra-articular bacterial-derived hyaluronic acid (Hyalubrix®) (HA) with local analgesia (mepivacaine) for osteoarthritis (OA) of the hip.

Methods

A pilot prospective, double-blind, 6-month randomized trial of 42 patients with hip OA. HA or mepivacaine was administered twice (once a month) under ultrasound guidance. Efficacy measurements included the Lequesne's algofunctional index, a visual analog scale for pain, concomitant use of analgesia, patient and physician global measurement, and safety.

Results

Patients in the HA group exhibited a significantly reduced Lequesne's algofunctional index 3 and 6 months after treatment (P < 0.001) and significantly reduced visual analog scale pain scores 3 and 6 months after treatment (P < 0.05) compared with the local anesthetic group. All primary and secondary measures were significantly improved versus baseline, but other than the above were not different from each other at 3 or 6 months. Adverse effects were minimal.

Conclusions

This comparative study suggests a beneficial effect and safety of intra-articular HA in the management of hip OA.

Trial registration number

ISRCTN39397064.
A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis
Authors: Le Goff Benoit , Soltner Elise , Charrier Céline , Maugars Yves , Rédini Françoise , Heymann Dominique , Berthelot Jean-Marie
Published: December 2009

Introduction

Osteoclasts play a key role in the pathogenesis of bone erosion and systemic bone mass loss during rheumatoid arthritis (RA). In this study, we aimed to determine the effect of methotrexate (MTX) and zoledronic acid (ZA), used alone or in combination, on osteoclast-mediated bone erosions and systemic bone mass loss in a rat model of collagen induced arthritis (CIA). We hypothesized that MTX and ZA could have an additive effect to prevent both bone erosion and systemic bone loss.

Methods

Arthritis was induced in 64 female Sprague-Dawley rats. After the clinical onset of CIA, rats were assigned to treatment with MTX (1 mg/kg/week), ZA (100 μg/kg twice weekly), both treatments at the same regimens, or vehicle. Arthritis score and paw thickness were recorded twice weekly. The rats were sacrificed on D28 and hind paws were removed for radiographic, histological and immunohistochemical analysis. The effects of treatments on osteoclastogenesis were determined by Tartrate resistant acid phosphatase (TRAP) staining. Micro-CT of the tibia was carried out for histomorphometric analysis. Bone mass density was evaluated by densitometry.

Results

MTX significantly decreased the severity of CIA, whereas ZA slightly exacerbated it. When these two drugs were used in combination, MTX prevented the pro-inflammatory effect of ZA. The combination of ZA with MTX was more effective than MTX alone for reducing structural joint damage with a dramatic decrease of osteoclasts' number in the eroded joints. However, MTX alone also significantly reduced the number of osteoclasts and the number of CD68+ mononuclear cells. ZA alone, or ZA with MTX, significantly increased the systemic bone mass density measured by densitometry and bone volume on histomorphometric analysis.

Conclusions

A combination of MTX and ZA prevented both bone erosion and systemic bone loss in a rat model of arthritis. Both treatments independently decreased the number of osteoclasts in the eroded joint. However, while MTX probably acts mainly through a decrease of inflammation, ZA has a direct effect on osteoclasts, allowing a dramatic down-regulation of these cells in inflamed joints. These two different mechanisms of action provide support for the use of a combination of these two drugs to improve the prevention of structural joint damage in RA.
Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast
Authors: Maia Ana-Teresa , Spiteri Inmaculada , Lee Alvin JX , O'Reilly Martin , Jones Linda , Caldas Carlos , Ponder Bruce AJ
Published: December 2009

Introduction

Normal gene expression variation is thought to play a central role in inter-individual variation and susceptibility to disease. Regulatory polymorphisms in cis-acting elements result in the unequal expression of alleles. Differential allelic expression (DAE) in heterozygote individuals could be used to develop a new approach to discover regulatory breast cancer susceptibility loci. As access to large numbers of fresh breast tissue to perform such studies is difficult, a suitable surrogate test tissue must be identified for future studies.

Methods

We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1, TP53 and TRXR2) in breast tissue (n = 40) and fresh blood (n = 170) of healthy individuals and EBV-transformed lymphoblastoid cells (n = 19). Differential allelic expression ratios were determined by Taqman assay. Ratio distributions were compared using t-test and Wilcoxon rank sum test, for mean ratios and variances respectively.

Results

We show that differential allelic expression is common among these 12 candidate genes and is comparable between breast and blood (fresh and transformed lymphoblasts) in a significant proportion of them. We found that eight out of nine genes with DAE in breast and fresh blood were comparable, as were 10 out of 11 genes between breast and transformed lymphoblasts.

Conclusions

Our findings support the use of differential allelic expression in blood as a surrogate for breast tissue in future studies on predisposition to breast cancer.
Towards accurate imputation of quantitative genetic interactions
Authors: Ulitsky Igor , Krogan Nevan J , Shamir Ron
Published: December 2009

Recent technological breakthroughs have enabled high-throughput quantitative measurements of hundreds of thousands of genetic interactions among hundreds of genes in Saccharomyces cerevisiae. However, these assays often fail to measure the genetic interactions among up to 40% of the studied gene pairs. Here we present a novel method, which combines genetic interaction data together with diverse genomic data, to quantitatively impute these missing interactions. We also present data on almost 190,000 novel interactions.
Reduced T cell expansion by a superantigen as a result of impaired B cell development in mice deficient for the p85α regulatory subunit of PI3K
Authors: Arimura Yutaka , Ezaki Taichi , Koyanagi Madoka , Uchiyama Takehiko , Koyasu Shigeo , Yagi Junji
Published: December 2009

PI3K p85α subunit alters the superantigen presentation capacity of B cells and indirectly modulates the magnitude of the T cell response.

PI3K plays crucial roles in the immune system. Mice deficient for p85α, a major regulatory subunit of class IA PI3K, show various defects and alterations in B cells, mast cells, macrophages, and DCs, and peripheral T cells are reportedly normal, at least in vitro. In normal mice, long-term exposure to a SAg, SEA, in vivo induced a high level of the protracted expansion of SEA-reactive Vβ3+CD4+ T cells, whereas the same treatment induced T cell expansion in p85α-deficient mice but to a much lesser extent than in normal mice. However, mixed bone marrow chimera mice, which have normal and p85α-deficient T and B cells, demonstrated equal responses of both T cells following stimulation with a SEA pump. In reciprocal cotransfer experiments of T and B cells from normal and p85α-deficient mice into Rag2-deficient mice, followed by SEA stimulation, p85α-deficient T cells revealed much higher proliferative capacity in the presence of normal B cells than did normal T cells with p85α-deficient B cells. Histologically, a marked B cell reduction was observed in the follicles and MZ of the spleen, and DCs accumulated in the MZ. In addition, p85α-deficient B cells had a low level of MHC class II expression. Collectively, these data suggested that the PI3K p85α subunit alters the SAg presentation capacity of B cells and indirectly modulates the magnitude of the T cell response, which may affect the protection against SEA-containing bacteria.
A GMCSF-neuroantigen fusion protein is a potent tolerogen in experimental autoimmune encephalomyelitis (EAE) that is associated with efficient targeting of neuroantigen to APC
Authors: Blanchfield J Lori , Mannie Mark D
Published: December 2009

This study shows that a DC-targeting, antigen-specific therapeutic is capable of inhibiting an ongoing inflammatory autoimmune disease.

Cytokine-NAg fusion proteins represent an emerging platform for specific targeting of self-antigen to particular APC subsets as a means to achieve antigen-specific immunological tolerance. This study focused on cytokine-NAg fusion proteins that targeted NAg to myeloid APC. Fusion proteins contained GM-CSF or the soluble extracellular domain of M-CSF as the N-terminal domain and the encephalitogenic 69–87 peptide of MBP as the C-terminal domain. GMCSF-NAg and MCSF-NAg fusion proteins were ∼1000-fold and 32-fold more potent than NAg in stimulating antigenic proliferation of MBP-specific T cells, respectively. The potentiated antigenic responses required cytokine-NAg covalent linkage and receptor-mediated uptake. That is, the respective cytokines did not potentiate antigenic responses when cytokine and NAg were added as separate molecules, and the potentiated responses were inhibited specifically by the respective free cytokine. Cytokine-dependent targeting of NAg was specific for particular subsets of APC. GMCSF-NAg and MCSF-NAg targeted NAg to DC and macrophages; conversely, IL4-NAg and IL2-NAg fusion proteins, respectively, induced an ∼1000-fold enhancement in NAg reactivity in the presence of B cell and T cell APC. GMCSF-NAg significantly attenuated severity of EAE when treatment was completed before encephalitogenic challenge or alternatively, when treatment was initiated after onset of EAE. MCSF-NAg also had significant tolerogenic activity, but GMCSF-NAg was substantially more efficacious as a tolerogen. Covalent GMCSF-NAg linkage was required for prevention and treatment of EAE. In conclusion, GMCSF-NAg was highly effective for targeting NAg to myeloid APC and was a potent, antigen-specific tolerogen in EAE.
Proteome bioprofiles distinguish between M1 priming and activation states in human macrophages
Authors: Brown Joseph N , Wallet Mark A , Krastins Bryan , Sarracino David , Goodenow Maureen M
Published: December 2009

Intracellular macrophage protein bioprofiles are shown as an effective new approach to fingerprint distinct cellular activation states.

Macrophage activation is a dynamic process that results in diverse functional outcomes ranging from immunoregulation to inflammation. The proinflammatory, or M1, response is a complex, bimodal progression composed of a “prime,” classically through IFN-γ, and “trigger,” such as LPS. To characterize the physiological response of M1 activation, a systems biology approach was applied to determine the intracellular proteome bioprofiles of IFN-γ- and LPS-treated primary human macrophages. Our goal was to develop intracellular proteomic fingerprints to serve as novel correlates of macrophage priming and/or activation to augment the existing approaches of analyzing secreted cytokines and cell-surface protein expression. The majority of the proteome, ∼78%, remained stable during activation, representing the core proteome. In contrast, three distinct patterns defined response proteomes: IFN-γ-specific, LPS-specific, or IFN-γ- and LPS-shared or M1-specific. Although steady-state expression levels of proteins involved in energy metabolism and immune response were increased during priming and triggering, changes in protein and fatty acid metabolism, signaling, and transport pathways were most apparent. Unique proteomic fingerprints distinguish among IFN-γ-specific, LPS-specific, or M1-specific activation states and provide a clear molecular, archeological profile to infer recent history of cells, as well as correlates for chronic macrophage activation in health and disease.
β2-Integrins in demyelinating disease: not adhering to the paradigm
Authors: Hu Xianzhen , Wohler Jillian E , Dugger Kari J , Barnum Scott R
Published: December 2009

Experimental autoimmune encephalomyelitis as a model for demyelinating disease challenges the mindset that β2-integrins are redundant in function and potential therapeutic targets for multiple sclerosis.

The β2-integrins are a subfamily of integrins expressed on leukocytes that play an essential role in leukocyte trafficking, activation, and many other functions. Studies in EAE, the animal model for multiple sclerosis, show differential requirements for β2-integrins in this disease model, ranging from critical in the case of LFA-1 (CD11a/CD18) to unimportant in the case of CD11d/CD18. Importantly, expression of β2-integrins on T cell subsets provides some clues as to the function(s) these adhesion molecules play in disease development. For example, transferred EAE studies have shown that Mac-1 (CD11b/CD18) expression on αβ T cells is critical for disease development, and the absence of LFA-1 on Tregs in recipient mice results in exacerbated disease. In this review, we summarize recent findings regarding the role of β2-integrins in demyelinating disease and new information about the role of β2-integrins with respect to alterations in Treg numbers and function. In addition, we discuss the potential for targeting β2-integrins in human demyelinating disease in light of the recent animal model studies.
Working in theAndZone: Comparative Literature and Translation
Authors: BERMANN SANDRA
Published: December 2009

“Working in the And Zone: Comparative Literature and Translation” argues that in conjunction with translation and translation studies comparative literature can offer new energy and purpose to the humanities today. The paper considers the changing roles of comparative literature in the twentieth century, as well as the recent importance of translation and translation studies to our field. Pointing to some deep similarities of method and aim between the two areas of study—particularly their dependence upon the analogical and abductive methods associated with and—it also underscores some key differences. I argue above all for the gains to be had in “thinking translation” as we go about our increasingly transnational and interdisciplinary teaching and writing in comparative literature. These gains include a range of new questions affecting what we mean by “text,” and “close reading,” as well as political, religious, and commercial issues connected to the writing and transmission of literary works. They also include an invigorated awareness of the ways in which questions of “foreign” and “home,” other and same, might find a place in a more dialogic and responsive mode of reading. In ways such as these, thinking translation in tandem with comparative literature will encourage the kind of collaborative re-imaginings especially important to the humanities of the twenty-first century.
Decision-Theoretic Paradoxes as Voting Paradoxes
Authors: Briggs Rachael
Published: December 2009

It is a platitude among decision theorists that agents should choose their actions so as to maximize expected value. But exactly how to define expected value is contentious. Evidential decision theory (henceforth EDT), causal decision theory (henceforth CDT), and a theory proposed by Ralph Wedgwood that this essay will call benchmark theory (BT) all advise agents to maximize different types of expected value. Consequently, their verdicts sometimes conflict. In certain famous cases of conflict—medical Newcomb problems—CDT and BT seem to get things right, while EDT seems to get things wrong. In other cases of conflict, including some recent examples suggested by Andy Egan, EDT and BT seem to get things right, while CDT seems to get things wrong. In still other cases, EDT and CDT seems to get things right, while BT gets things wrong.

It's no accident, this essay claims, that all three decision theories are subject to counterexamples. Decision rules can be reinterpreted as voting rules, where the voters are the agent's possible future selves. The problematic examples have the structure of voting paradoxes. Just as voting paradoxes show that no voting rule can do everything we want, decision-theoretic paradoxes show that no decision rule can do everything we want. Luckily, the so-called “tickle defense” establishes that EDT, CDT, and BT will do everything we want in a wide range of situations. Most decision situations, this essay argues, are analogues of voting situations in which the voters unanimously adopt the same set of preferences. In such situations, all plausible voting rules and all plausible decision rules agree.
Epistemic Invariantism and Speech Act Contextualism
Authors: Turri John
Published: December 2009

In this essay I show how to reconcile epistemic invariantism with the knowledge account of assertion. My basic proposal is that we can comfortably combine invariantism with the knowledge account of assertion by endorsing contextualism about speech acts. My demonstration takes place against the backdrop of recent contextualist attempts to usurp the knowledge account of assertion, most notably Keith DeRose's influential argument that the knowledge account of assertion spells doom for invariantism and enables contextualism's ascendancy.
The Free Officers and the Comrades: The Sudanese Communist Party and Nimeiri Face-to-Face, 1969–1971
Authors: Gresh Alain
Published: December 2009

Africa's largest country, Sudan, is first and foremost part of the Arab world, sensitive to the political tides that sweep the Arab peoples from the Atlantic to the Persian Gulf. Like other members of the Arab League, Sudan was taken by surprise by the defeat of 1967. It was shaken by the tidal wave that later engulfed Libya, Lebanon, Iraq, and Syria, and on May 25, 1969, a military regime took over in Khartoum. Its ideology was Arab nationalism infused with socialism; its social base, the army and the urban classes; and its model, the Nasserist experiment.
Darfur and the Crisis of Governance in Sudan: A Left Perspective
Authors: Hassan Salah M.
Published: December 2009

This essay highlights the selective ways in which the conflict in Darfur has been presented, represented, and used by a range of actors in and outside of Sudan to promote their own agendas and interests. It draws attention to the urgency of apprehending the politics of representation around Darfur “from within.” Focusing on Sudan's historically strong civil society, the essay elucidates how the Sudanese civil society's analysis of the country's conflicts eschews oversimplified binary oppositions, such as “Arab North” versus “Christian/animist South” or “Arab” versus “African,” as in the case of Darfur. Hassan argues in favor of looking at the origins of these conflicts as manifestations of unequal development and historic injustices perpetrated against the margins by the ruling class of Arabized elites. In the process, Hassan reveals the vigorous engagement of Sudanese at all levels in the Darfur crisis, as well as other areas of conflict currently engulfing the country. The essay urges the need to foreground Sudanese voices if a genuine resolution to the country's manifold conflicts is to be pursued.
It Is Time for Change
Authors: Adlan al-Khatim
Published: December 2009

In this critical essay on the Sudanese Communist Party (SCP), the late philosopher and former SCP member al-Khatim Adlan maps out the multiple histories of the efforts of Sudanese Marxists to transform the SCP into a massive social and populist movement at the national level. Drawing on Abdel Khaliq Mahgoub's powerful articulations of Marxism, political economy, leadership, and labor theories, Adlan addresses the rich experiences of the SCP in its relentless efforts at beating the odds of conservative politics. His misgivings about the SCP at the time of his resignation embody the spirit of critical debate among Sudanese Marxists in relation to principles of democratic centralism, the role of intellectuals, and the linkages of theory to praxis that they helped to create. Adlan also thoroughly analyzes the principles and mechanisms surrounding the fundamental premises for revamping the SCP.
The Dilemma of the Southern Intellectual: Is It Justified?
Authors: Garang Joseph U.
Published: December 2009

In this 1971 essay, Joseph Garang, a leading Sudanese Marxist intellectual and activist in the 1960s and early 1970s, makes a case for a united Sudan. He draws from the wealth of Marxist theory to elucidate the political economy of power and marginality that undergirds the ethnic nationalism that plagued the country and silenced the voices of those who attempted to reckon with structural inequality. In addition to their obvious contributions to Sudanese leftist historiography, Garang's views are as relevant today as they were decades ago. Garang scrupulously examines multicultural identities, justice and marginality, and ethnic secessionist politics.
Finding Our Way
Authors: Bogavac Milena , Lolić Miloš
Published: December 2009

Tom Sellar speaks with two of Serbia's leading young theater artists—playwright Milena Bogavac and director Miloš Lolić, both in their twenties. In this interview, he asks them about the aesthetic and political aspirations of the next generation of theatermakers in Serbia.
Bambiland
Authors: Jelinek Elfriede
Published: December 2009

Translated by Lilian Friedberg

Original title: bambiland © 2004 by Rowohlt Verlag GmbH, Reinbek bei Hamburg. Stage rights: Rowohlt Theater Verlag, Reinbek bei Hamburg. English translation © 2005 by Lilian Friedberg. All rights reserved. No part of this play may be reproduced in any form or by any means, electronic or mechanical, including photocopying, recording, and information storage and retrieval systems, without permission.

caution: Professionals and amateurs are hereby warned that, being fully protected under the copyright laws of the United States of America, the British Commonwealth, including the Dominion of Canada, and all other countries of the Copyright Union, this play is subject to royalty. All rights, including professional, amateur, motion picture, recitation, lecturing, public reading, radio and television broadcasting, and translation into foreign languages, are strictly reserved. Particular emphasis is laid on the questions of readings, permission for which must be secured from the authors. This translation was completed with the generous support of the Goethe Institute.
Rap1 and its effector KRIT1/CCM1 regulate β-catenin signaling
Authors: Glading Angela J. , Ginsberg Mark H.
Published: December 2009

KRIT1, also called CCM1, is a member of a multiprotein complex that contains the products of the CCM2 and PDCD10 (also known as CCM3) loci. Heterozygous loss of any of the genes that encode these proteins leads to cerebral cavernous malformations (CCM), which are vascular lesions that are found in around 0.5% of humans. KRIT1 mediates the stabilization of β-catenin-containing endothelial cell-cell junctions downstream of the Rap1 GTPase. Here, we report that Rap1 and KRIT1 are negative regulators of canonical β-catenin signaling in mice and that hemizygous Krit1 deficiency exacerbates β-catenin-driven pathologies. Depletion of endothelial KRIT1 caused β-catenin to dissociate from vascular endothelial (VE)-cadherin and to accumulate in the nucleus with consequent increases in β-catenin-dependent transcription. Activation of Rap1 inhibited β-catenin-dependent transcription in confluent endothelial cells; this effect required the presence of intact cell-cell junctions and KRIT1. These effects of KRIT1 were not limited to endothelial cells; the KRIT1 protein was expressed widely and its depletion increased β-catenin signaling in epithelial cells. Moreover, a reduction in KRIT1 expression also increased β-catenin signaling in vivo. Hemizygous deficiency of Krit1 resulted in a ~1.5-fold increase in intestinal polyps in the ApcMin/+ mouse, which was associated with increased β-catenin-driven transcription. Thus, KRIT1 regulates β-catenin signaling, and Krit1+/− mice are more susceptible to β-catenin-driven intestinal adenomas.
Plastic loads for 90° thick-walled elbows under combined pressure and bending
Authors: Kim Y-J , Je J-H , Oh C-S , Han J-J , Budden P J
Published: December 2009

This paper extends plastic load solutions proposed by the authors for 90° thin-walled elbows, to thick-walled elbows, based on three-dimensional finite element analyses using the large geometry change option. For loading, internal pressure, in-plane, and out-of-plane bending, as well as combined pressure and bending, are considered. As no experimental data are available for thick-walled elbows, the proposed solutions are indirectly validated by comparing thin-walled solutions with exiting experimental data.
Deformation characteristics and mechanisms of the cold rotary forging of a ring workpiece
Authors: Han X H , Hua L
Published: December 2009

Cold rotary forging is an advanced but very complex incremental metal plastic-forming technology under coupled effects with multifactors. Previous research concentrates mainly on the study of the cold rotary forging process of a cylindrical workpiece and thus it is essential to explore the deformation characteristics and mechanisms of the cold rotary forging of a ring workpiece in order to use rotary forging presses with maximum efficiency. In the current paper, numerous simulations have been carried out based on a valid three-dimensional elastic-plastic dynamic explicit finite element model developed using ABAQUS software. Through these simulations, the interactive effects of three main processing parameters, the feed rate v of the lower die, rotational speed n, and inclination angle γ of the upper die on the cold rotary forging process of a ring workpiece, have been thoroughly explored. Furthermore, a comprehensive and decisive factor in cold rotary forging, namely the equivalent feed amount per revolution Q, is put forward, and its effects on the forming process have also been thoroughly revealed. The results obtained are explained with regard to the plastic penetrating states of the deformed ring workpiece. The results of this research thoroughly reveal the deformation characteristics and mechanisms of cold rotary forging of a ring workpiece, and provide valuable guidelines for optimizing the processing parameters so as to control precisely the cold rotary forging process of a ring workpiece.
Estimation of the radial force using a disturbance force observer for a magnetically levitated centrifugal blood pump
Authors: Pai C N , Shinshi T , Shimokohbe A
Published: December 2009

Evaluation of the hydraulic forces in a magnetically levitated (maglev) centrifugal blood pump is important from the point of view of the magnetic bearing design. Direct measurement is difficult due to the absence of a rotor shaft, and computational fluid dynamic analysis demands considerable computational resource and time. To solve this problem, disturbance force observers were developed, using the radial controlled magnetic bearing of a centrifugal blood pump, to estimate the radial forces on the maglev impeller. In order to design the disturbance observer, the radial dynamic characteristics of a maglev impeller were evaluated under different working conditions. It was observed that the working fluid affects the additional mass and damping, while the rotational speed affects the damping and stiffness of the maglev system. Based on these results, disturbance force observers were designed and implemented. The designed disturbance force observers present a bandwidth of 45 Hz. In non-pulsatile conditions, the magnitude of the estimated radial thrust increases in proportion to the flowrate, and the rotational speed has little effect on the force direction. At 5 l/min against 100 mmHg, the estimated radial thrust is 0.95 N. In pulsatile conditions, this method was capable of estimating the pulsatile radial thrust with good response.
Modelling cement augmentation: A comparative experimental and finite element study at the continuum level
Authors: Zhao Y , Jin Z M , Wilcox R K
Published: December 2009

Subject-specific computational models of anatomical components can now be generated from image data and used in the assessment of orthopaedic interventions. However, little work has been undertaken to model cement-augmented bone using these methods. The purpose of this study was to investigate different methods of representing a trabecular-like material (open-cell polyurethane foam, Sawbone, Sweden) augmented with poly(methyl methacrylate) (PMMA) bone cement in a finite element (FE) model. Three sets of specimens (untreated, fully augmented with cement, partially augmented with cement) were imaged using micro computed tomography (μCT) and tested under axial compression. Subject-specific continuum level FE models were built based on the μCT images. Using the first two sets of models, the material conversion factors between image greyscale and mechanical properties for the pure synthetic bone and cement-augmented composite were determined iteratively by matching the FE predictions to the experimental measurements. By applying these greyscale related mechanical properties to the FE models of the partially augmented specimens, the predicted stiffness was found to be more accurate (∼ 5 per cent error) than using homogeneous properties for the augmented and synthetic bone regions (∼ 18 per cent error). It was also found that the predicted stiffness using the modulus of pure cement to define the augmented region was overestimated, and generally the apparent elastic modulus was dominated by the properties of the synthetic bone.
Molecular Simulations of Photoaddition Selectivity and Chirality in Challenging Photochemical Reactions
Authors: Somekawa Kenichi , Odo Yuka , Shimo Tetsuro
Published: December 2009

The origins of cycloaddition selectivities and chirality controls in particular and challenging photochemical reactions were examined. The profiles of the energies and stereochemical changes of the photoreactions were characterized by molecular simulations using dynamic molecular orbital methods. The photoreactions possess particular factors which are not explained by the frontier molecular orbital (FMO) theory. Particular photoreactions are examined by following the addition selectivities and two chiral controls by use of chiral hosts. (1) Species-(singlet or triplet), peri-, site-, regio-, and stereo-selectivities in the [2 + 2]cycloadditions and [4 + 4]cycloadditions of 2-pyridone (1). (2) Inversion of regioselectivity (hh/ht ratio) by the linkage-length in intramolecular [2 + 2]cycloadditions of α,β-unsaturated furanones 7 and by the alkene ring-size in intermolecular [2 + 2]cycloadditions of cycloalkenecarboxylates 11–13 with 2-cyclohexenone (10). (3) The occurrence of the hydrogen-shift reaction in the [2 + 2]photocycloaddition system between 4-hydoxycoumarin (17) and 3,4-dihydro-2H-pyran (18o). (4) Chiral control of selective [4π]-electrocyclic isomerizations of 1 to photopyridone 20 by hydrogen-bonding of chiral amide hosts 21. The singlet excited state, 1* was inferred to be enantiomeric conformers, 1*(+) and 1*(−), and the complex 1·(l)-21 proceeds to 1*(+)·(l)-21, followed by quenching to (R)-20. (5) Sensational chiral isomerization of (Z)-cyclooctene (28Z) to chiral (E)-cyclooctene (29E) by chiral benzenepolycarboxylates (30). 28Z was inferred to accompany asymmetric 28Z and the diastereomeric exciplexes Ex1 (28Z·30*) and proceeds with chiral isomerization via the one-sided rotation to Ex2 (29E*·30), followed by quenching to chiral 29E. The molecular simulations for the photoreactions by MOPAC-PM5, (PM3 for hydrogen-bonding), UCIS (for singlets), and UB3LYP (for triplets) are found to be successful and show that the origin of the photoreaction selectivities is essentially determined by the first step (TS1) energies and the stereochemistries are dependent on the excited species presented in the Concluding Remarks. We also propose some applications of the molecular simulations.
Low-Frequency Isotropic Raman Spectra of Concentrated Aqueous KX (X: Cl, Br, NO3, and SCN) Solutions
Authors: Kameda Yasuo , Ishikawa Marie , Amo Yuko , Usuki Takeshi
Published: December 2009

Polarized Raman spectra for concentrated aqueous KX solutions (X: Cl, Br, NO3, and SCN) were measured in the frequency range of 30 ≤−1 in order to find the totally symmetric stretching vibrational mode of hydrated K+. The observed polarized peak intensities of the intermolecular vibrational mode at−1 in the isotropic spectra for KCl and KBr solutions exhibit systematic increase with increasing solute content. Polarized components at−1 were observed in the isotropic spectra for 5 mol % KNO3 and 7 mol % KSCN solutions, respectively. The position of these polarized peaks were found to shift to lower frequency by 7–15 cm−1 in D2O solutions, which is consistent with the expected value of the H/D isotopic shift calculated for the totally symmetric vibrational mode of the hydrated K+, K+(H2O)6.≤ 1000 cm= 160–180 cm= 166 and 167 cm