bluuebunny/crossref_metadata_2025 huggingface dataset:
Sintering Behavior, Microstructure, and Mechanical Properties: A Comparison among Pressureless Sintered Ultra-Refractory Carbides
Authors: Silvestroni Laura , Sciti Diletta
Published: December 2010

Nearly fully dense carbides of zirconium, hafnium, and tantalum were obtained by pressureless sintering at 1950°C with the addition of 5–20 vol% of MoSi2. Increasing the amount of sintering aid, the final density increased too, thanks to the formation of small amounts of liquid phase constituted by M-Mo-Si-O-C, where M is either Zr, Hf, or Ta. The matrices of the composites obtained with the standard procedure showed faceted squared grains; when an ultrasonication step was introduced in the powder treatment, the grains were more rounded and no exaggerated grains growth occurred. Other secondary phases observed in the microstructure were SiC and mixed silicides of the transition metals. Among the three carbides prepared by pressurless sintering, TaC-based composites had the highest mechanical properties at room temperature (strength 590 MPa, Young's modulus 480 GPa, toughness 3.8 MPa·m1/2). HfC-based materials showed the highest sinterability (in terms of final density versus amount of sintering aid) and the highest high-temperature strength (300 MPa at 1500  °C).
Unified Dark Matter Scalar Field Models
Authors: Bertacca Daniele , Bartolo Nicola , Matarrese Sabino
Published: December 2010

We analyze and review cosmological models in which the dynamics
of a single scalar field accounts for a unified description of the Dark Matter and Dark Energy sectors, dubbed Unified Dark Matter (UDM) models. In this framework, we consider the general Lagrangian of
k‐essence, which allows to find solutions around which the scalar field describes the desired mixture of Dark Matter and Dark Energy. We also discuss static and spherically symmetric solutions of Einstein′s equations for a scalar field with noncanonical kinetic term, in connection with galactic halo rotation curves.
Effects ofFlos carthamion CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats
Authors: Liu Gaofeng , Liu Yan , Liu Rui , Dong Feng , Zhang Zhiren
Published: November 2010

Flos carthamiis a traditional Chinese herbal medicine. Clinically, theFlos carthamiInjection has been used concomitantly with other Western drugs and may be used concomitantly withβ‐blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether there is an effect ofFlos carthamion CYP2D6 and the consequences of such an effect. Concern is raised regarding the possible herb‐drug interaction. In this report, the effects ofFlos carthamion the activity of CYP2D6in vivoandin vitroand on the pharmacokinetics of metoprolol, in rats, are investigated. To assess the inhibitory potency ofFlos carthami, the concentration associated with 50% inhibition (IC50) of dextromethorphan metabolism was determined based on the concentration‐inhibition curves. The inhibitory effect ofFlos carthamion CYP2D6 was also compared with cimetidinein vitro.Flos carthamicould significantly inhibit CYP2D6 in rats bothin vitroandin vivo(P< .05) and could slow down the metabolic rate of metoprolol as suggested by prolonged t1/2(67.45%), by increasedCmax(74.51%) and AUC0−∞(76.89%). These results suggest that CYP2D6 is a risk factor whenFlos carthamiis administered concomitantly with metoprolol or other CYP2D6 substrates.
Flow Cytometric Detection of the Classical Hodgkin Lymphoma: Clinical and Research Applications
Authors: Roshal Mikhail , Wood Brent L. , Fromm Jonathan R.
Published: November 2010

Classical Hodgkin lymphoma (CHL) is a relatively uncommon B cell-derived neoplasm that presents with rare malignant cells in an abundant reactive background. The diagnosis of CHL currently relies on a combination of morphologic findings and immunohistochemical stains. With the exception of rare cases with dramatically increased malignant populations, isolation of pure viable tumor cells has not been historically possible. Recently, a reliable flow cytometric assay for direct detection and isolation of the malignant cells in this disease has been developed. This assay has proven useful diagnostically and has been clinically validated to have a very high sensitivity and nearly absolute specificity for the diagnosis of CHL in routine clinical samples. This paper describes the methodology for the flow cytometric detection of CHL in clinical samples as well as current state of evaluation of background lymphocytes as an adjunct diagnostic test. Also discussed are exciting research applications of the direct isolation of viable tumor cells in CHL. The current state of flow cytometric evaluation of nodular lymphocyte predominant Hodgkin lymphoma and T cell-rich large B cell lymphoma is also briefly discussed.
Activation of Mitogen-Activated Protein Kinase in Descending Pain Modulatory System
Authors: Imbe Hiroki , Senba Emiko , Kimura Akihisa , Donishi Tomohiro , Yokoi Isao , Kaneoke Yoshiki
Published: December 2010

The descending pain modulatory system is thought to undergo plastic changes following peripheral tissue injury and exerts bidirectional (facilitatory and inhibitory) influence on spinal nociceptive transmission. The mitogen-activated protein kinases (MAPKs) superfamily consists of four main members: the extracellular signal-regulated protein kinase1/2 (ERK1/2), the c-Jun N-terminal kinases (JNKs), the p38 MAPKs, and the ERK5. MAPKs not only regulate cell proliferation and survival but also play important roles in synaptic plasticity and memory formation. Recently, many studies have demonstrated that noxious stimuli activate MAPKs in several brain regions that are components of descending pain modulatory system. They are involved in pain perception and pain-related emotional responses. In addition, psychophysical stress also activates MAPKs in these brain structures. Greater appreciation of the convergence of mechanisms between noxious stimuli- and psychological stress-induced neuroplasticity is likely to lead to the identification of novel targets for a variety of pain syndromes.
Reduction of Collimator Correction Artefacts with Bayesian Reconstruction in Spect
Authors: Kangasmaa Tuija , Sohlberg Antti , Kuikka Jyrki T.
Published: December 2010

Poor resolution of single photon emission computed tomography (SPECT) has degraded its use in clinical practice. Collimator correction has been shown to improve the reconstructed resolution, but the correction can generate ringing artefacts, which lower image quality. This paper investigates whether Bayesian reconstruction methods could reduce these artefacts. We have applied and tested three Bayesian reconstruction methods: smoothing prior, median root prior, and anatomical prior. To demonstrate the efficacy of these methods, we compared their physical and visual performance both in phantom and patient studies. All the three Bayesian reconstruction methods reduced the collimator correction artefacts. Images reconstructed using the smoothing prior and the median root prior had slightly lower contrast than the standard reconstruction with collimator correction, whereas the anatomical prior produced images with good resolution and contrast.
Osteoid Osteoma: Can Impedance Levels in Radiofrequency Thermocoagulation Predict Recurrence?
Authors: Ockendon Matthew , Gregory Jonathan J. , Cribb Gillian L. , Cool W. Paul , Mangham D. Charles , Lalam Radhesh
Published: November 2010

Objective. To evaluate rise in impedance during percutaneous radiofrequency thermocoagulation (PRFTC) of osteoid osteomas as a predictor of local recurrence.Design and Patients. A prospective study of 23 patients (24 PRFTC procedures) with minimum of 2.25-year followup (average 3.3 years). Average age 19.6 years (range 4–44), sex ratio 15 : 8 (male : female), 16 nondiaphyseal, 7 diaphyseal.Results. In 19 procedures, an increase in impedance was measured—no recurrences have occurred in this group to date. In 5 procedures, no increase in impedance was seen (3 non-diaphyseal, 2 diaphyseal), and 1 recurrence has been seen in this group to date. This difference is statistically significant with aPvalue of .05.
Power Prior Elicitation in Bayesian Quantile Regression
Authors: Alhamzawi Rahim , Yu Keming
Published: December 2010

We address a quantile dependent prior for Bayesian quantile regression. We extend the idea of the power prior distribution in Bayesian quantile regression by employing the likelihood function that is based on a location‐scale mixture representation of the asymmetric Laplace distribution. The propriety of the power prior is one of the critical issues in Bayesian analysis. Thus, we discuss the propriety of the power prior in Bayesian quantile regression. The methods are illustrated with
both simulation and real data.
The Tale of Protein Lysine Acetylation in the Cytoplasm
Authors: Sadoul Karin , Wang Jin , Diagouraga Boubou , Khochbin Saadi
Published: November 2010

Reversible posttranslational modification of internal lysines in many cellular or viral proteins is now emerging as part of critical signalling processes controlling a variety of cellular functions beyond chromatin and transcription. This paper aims at demonstrating the role of lysine acetylation in the cytoplasm driving and coordinating key events such as cytoskeleton dynamics, intracellular trafficking, vesicle fusion, metabolism, and stress response.
Targeting STAT3 in Adoptively Transferred T Cells Promotes Their In Vivo Expansion and Antitumor Effects
Authors: Kujawski Maciej , Zhang Chunyan , Herrmann Andreas , Reckamp Karen , Scuto Anna , Jensen Michael , Deng Jiehui , Forman Stephen , Figlin Robert , Yu Hua
Published: December 2010

Adoptive cell therapy with engineered T cells to improve natural immune response and antitumor functions has shown promise for treating cancer. However, the requirement for extensive ex vivo manipulation of T cells and the immunosuppressive effects of the tumor microenvironment limit this therapeutic modality. In the present study, we investigated the possibility to circumvent these limitations by engineering Stat3 -deficient CD8+ T cells or by targeting Stat3 in the tumor microenvironment. We show that ablating Stat3in CD8+ T cells prior to their transfer allows their efficient tumor infiltration and robust proliferation, resulting in increased tumor antigen-specific T-cell activity and tumor growth inhibition. For potential clinical translation, we combined adoptive T-cell therapy with a Food and Drug Administration–approved tyrosine kinase inhibitor, sunitinib, in renal cell carcinoma and melanoma tumor models. Sunitinib inhibited Stat3 in dendritic cells and T cells and reduced conversion of transferred FoxP3− T cells to tumor-associated regulatory T cells while increasing transferred CD8+ T-cell infiltration and activation at the tumor site, leading to inhibition of primary tumor growth. These data show that adoptively transferred T cells can be expanded and activated in vivo either by engineering Stat3-silenced T cells or by targeting Stat3 systemically with small-molecule inhibitors. Cancer Res; 70(23); 9599–610. ©2010 AACR.
CDB-4124, a Progesterone Receptor Modulator, Inhibits Mammary Carcinogenesis by Suppressing Cell Proliferation and Inducing Apoptosis
Authors: Wiehle Ronald , Lantvit Daniel , Yamada Tohru , Christov Konstantin
Published: December 2010

CDB-4124 (Proellex or telapristone acetate) is a modulator of progesterone receptor (PR) signaling, which is currently employed in preclinical studies for prevention and treatment of breast cancer and has been used in clinical studies for treatment of uterine fibroids and endometriosis. Here we provide evidence for its action on steroid hormone-signaling, cell cycle–regulated genes and in vivo on mammary carcinogenesis. When CDB-4124 is given to rats at 200 mg/kg for 24 months, it prevents the development of spontaneous mammary hyperplastic and premalignant lesions. Also, CDB-4124 given as subcutaneous pellets at two different doses suppressed, dose dependently, N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis. The high dose (30 mg, over 84 days) increased tumor latency from 66 ± 24 days to 87 ± 20 days (P < 0.02), decreased incidence from 85% to 35% (P < 0.001), and reduced multiplicity from 3.0 to 1.1 tumors/animal (P < 0.001). Tumor burden decreased from 2.6 g/animal to 0.26 g/animal (P < 0.01). CDB-4124 inhibited cell proliferation and induced apoptosis in MNU-induced mammary tumors, which correlated with a decreased proportion of PR+ tumor cells and with decreased serum progesterone. CDB-4124 did not affect serum estradiol. In a mechanistic study employing T47D cells we found that CDB-4124 suppressed G1/G0–S transition by inhibiting CDK2 and CDK4 expressions, which correlated with inhibition of estrogen receptor (ER) expression. Taken together, these data indicate that CDB-4124 can suppress the development of precancerous lesions and carcinogen-induced ER+ mammary tumors in rats, and may have implications for prevention and treatment of human breast cancer. Cancer Prev Res; 4(3); 414–24. ©2011 AACR.
Función neuropsicológica en la fenilcetonuria tratada precozmente: Una revisión
Authors: Crossley Louise H. , Anderson Peter J.
Published: December 2010

La fenilcetonuria (FCU) es un error metabólico congénito que implica una deficiencia de la enzima fenilalanina hidroxilasa. Este proceso da lugar a niveles elevados de fenilalanina y niveles bajos de tirosina. Si no se administra tratamiento aparecen graves secuelas neuropatológicas y neuroconductuales. La puesta en práctica de la detección sistemática de recién nacidos y el tratamiento dietético precoz ha reducido significativamente esta morbilidad. A pesar de una función intelectual general relativamente conservada, en los pacientes con FCU tratados precozmente se detectan todavía sutiles deficiencias cognitivas y conductuales. Este trabajo aporta una revisión de los datos del deterioro de la elaboración de información, la función ejecutiva, la memoria, el aprendizaje, el aprovechamiento escolar y la conducta. En este trabajo también revisamos las dos teorías principales propuestas hasta la fecha en relación con los mecanismos subyacentes de las deficiencias cognitivas y conductuales halladas en pacientes con FCU tratados, concretamente la disfunción prefrontal y las anomalías de la sustancia blanca. Aunque es necesario ampliar la investigación, la literatura disponible hasta la fecha da a entender que los pacientes afectados de FCU tratados precozmente presentan un riesgo de deficiencias neuroconductuales insidiosas en toda una gama de dominios neuropsicológicos. Por lo tanto, los pacientes con FCU tienen que ser monitorizados minuciosamente para detectar precozmente estos problemas y aplicar intervenciones apropiadas capaces de asegurar que estos pacientes alcancen su pleno potencial.
Guidance for Removal of Fetal Bovine Serum from Cryopreserved Heart Valve Processing
Authors: Brockbank Kelvin G.M. , Heacox Albert E. , Schenke-Layland Katja
Published: December 2010

Bovine serum is commonly used in cryopreservation of allogeneic heart valves; however, bovine serum carries a risk of product adulteration by contamination with bovine-derived infectious agents. In this study, we compared fresh and cryopreserved porcine valves that were processed by 1 of 4 cryopreservation formulations, 3 of which were serum-free and 1 that utilized bovine serum with 1.4 M dimethylsulfoxide. In the first serum-free group, bovine serum was simply removed from the cryopreservation formulation. The second serum-free formulation had a higher cryoprotectant concentration, i.e. 2 M dimethylsulfoxide, in combination with a serum-free solution. A colloid, dextran 40, was added to the third serum-free group with 2 M dimethylsulfoxide due to theoretical concerns that removal of serum might increase the incidence of tissue cracking. Upon rewarming, the valves were inspected and subjected to a battery of tests. Gross pathology revealed conduit cracking in 1 of 98 frozen heart valves. Viability data for the cryopreserved groups versus the fresh group demonstrated a loss of viability in half of the comparisons (p < 0.05). No significant differences were observed between any of the cryopreserved groups, with or without bovine serum. Neither routine histology, autofluorescence-based multiphoton imaging nor semiquantitative second-harmonic generation microscopy of extracellular matrix components revealed any statistically significant differences. Biomechanics analyses also revealed no significant differences. Our results demonstrate that bovine serum can be safely removed from heart valve processing and that a colloid to prevent cracking was not required. This study provides guidance for the assessment of changes in cryopreservation procedures for tissues.
Inactivation of Bmp4 from the Tbx1 Expression Domain Causes Abnormal Pharyngeal Arch Artery and Cardiac Outflow Tract Remodeling
Authors: Nie Xuguang , Brown Christopher B. , Wang Qin , Jiao Kai
Published: December 2010

Maldevelopment of outflow tract and aortic arch arteries is among the most common forms of human congenital heart diseases. Both Bmp4 and Tbx1 are known to play critical roles during cardiovascular development. Expression of these two genes partially overlaps in pharyngeal arch areas in mouse embryos. In this study, we applied a conditional gene inactivation approach to test the hypothesis that Bmp4 expressed from the Tbx1 expression domain plays a critical role for normal development of outflow tract and pharyngeal arch arteries. We showed that inactivation of Bmp4 from Tbx1-expressing cells leads to the spectrum of deformities resembling the cardiovascular defects observed in human DiGeorge syndrome patients. Inactivation of Bmp4 from the Tbx1 expression domain did not cause patterning defects, but affected remodeling of outflow tract and pharyngeal arch arteries. Our further examination revealed that Bmp4 is required for normal recruitment/differentiation of smooth muscle cells surrounding the PAA4 and survival of outflow tract cushion mesenchymal cells.
Longevity Analysis of Currently Available Deep Brain Stimulation Devices
Authors: Halpern Casey H. , McGill Kathryn R. , Baltuch Gordon H. , Jaggi Jurg L.
Published: December 2010

Objective: There continues to be debate about the surgical technique, electrophysiology, and hardware used in deep brain stimulation (DBS), despite its widespread use in medically intractable Parkinson’s disease and essential tremor. This article is the first, to our knowledge, to compare the longevity of the available internal pulse generators (IPGs) of DBS (Kinetra and Soletra, Medtronics). Methods: We compared the elapsed time from the initial surgery to the first replacement of IPGs in patients with bilateral Soletra IPGs to those with the unilateral Kinetra IPG and analyzed the various stimulation parameters of each device. Results: The battery life of the Soletra system was significantly longer than that of the Kinetra and also allowed for higher voltages, longer use of monopolar mode, and a greater number of electrode contacts. Conclusions: Our findings support superior battery life and a greater capacity for titration to symptom control with bilateral Soletra IPGs.
Altered Expression of Tight Junction Proteins in Cyclosporine Nephrotoxicity
Authors: Lee Chang Hwa , Kim Sua , Kang Chong Myung , Kim Wan Young , Kim Jin , Kim Gheun-Ho
Published: December 2010

Background/Aims: The increased permeability of chloride in the distal cortical nephron in cyclosporine nephrotoxicity may involve the transcellular pathway mediated by the thiazide-sensitive Na+-Cl– cotransporter and/or the paracellular pathway mediated by the tight junctions (TJs). Methods: Cyclosporine was subcutaneously administered to Sprague-Dawley rats for 6 (7.5 mg/kg body weight) and 2 (25 mg/kg body weight) weeks, and immunoblot analysis and immunohistochemistry were carried out from the kidneys. Electrically tight epithelial Madin-Darby canine kidney (MDCK) I cells were exposed to cyclosporine for 72 h to measure changes in transepithelial electrical resistance (ΔTER). Results: Cyclosporine treatment induced a decrease in Na+-Cl– cotransporter in rat renal cortex. WNK4 protein was increased in both rat kidneys and MDCK I cells. Occludin was also increased in rat kidneys and MDCK I cells exposed to 100 ng/ml cyclosporine. In contrast, cyclosporine treatment induced a decrease in zonula occludens 1 protein abundance and no changes in claudin-1 and claudin-4 in both rat kidneys and MDCK I cells. As a measure of the barrier to small ions, ΔTER of MDCK monolayers was decreased by 100 ng/ml cyclosporine. Conclusion: Renal TJ proteins are affected by cyclosporine treatment. Changes in TJ protein assembly induced by altered expression of WNK4, occludin, and zonula occludens 1 may affect paracellular permeability.
Geropsychology: The Gender Gap in Human Aging – A Mini-Review
Authors: Kryspin-Exner Ilse , Lamplmayr Elisabeth , Felnhofer Anna
Published: December 2010

Differences between women and men in terms of gender gaps at late stages of their lives are the focus of this mini-review. We approach the matter by taking up the position of complex yet promising standpoints, the bio-psycho-social perspective on the one hand and approaches of developmental psychology on the other. Lifespan perspectives and the brain-behavior relationship are integrated and applied to geropsychological models. Research on gender differences is presented and examined, particularly regarding physiological and psychological differences between aging men and women; additionally, gender discrepancies in psychopathology are discussed. Prevailing concepts of ‘active aging’ are introduced and their implications for the review of divergent gender differences are considered.
Recent Developments in EU Environmental Policy and Law
Authors: Mertens Kathleen
Published: December 2010

This section briefly describes the significant political initiatives and acts of legislation adopted in the environmental field between December 2009 and June 2010.
The Dialectical Self-Concept II
Authors: Boucher Helen C.
Published: December 2010

Although there is growing evidence that dialectical thinkers express more inconsistency within the global self-concept, whether this holds true for inconsistency across roles and within specific roles has received little attention. I examine whether dialectical thinking is associated with less cross-role and within-role consistency and whether dialecticism moderates the relationship between self-consistency and subjective well-being, self-concept certainty, and felt authenticity. Participants completed measures of the above outcomes, a measure of dialectical thinking, and a self-description measure for both the global self-concept and within two roles (e.g., friend), from which I derived both cross-role and within-role consistency scores. Dialectical thinking predicted lower scores on both types of consistency, and in general dialecticism moderated the relationship between self-concept consistency and both subjective well-being and self-concept certainty. Dialecticism also moderated the relationship between cross-role consistency and authenticity, and the relationship between authenticity and subjective well-being. I conclude by discussing directions for future research.
Continuing Education Course #2: Current Understanding of Hemostasis
Authors: Gale Andrew J.
Published: December 2010

The goal of this review is to briefly summarize the two primary pathways of hemostasis, primary hemostasis and secondary hemostasis, as well as to summarize anticoagulant mechanisms and fibrinolysis. In addition, this review will discuss pathologies of hemostasis and the mechanisms of the various drugs that are available to impact these pathways to prevent either thrombosis or bleeding. While many of the main drugs that are used to treat disorders of hemostasis have been used for decades, greater understanding of hemostasis has led to development of various new drugs that have come onto the market recently or are close to coming onto the market. Thus, improved understanding of hemostasis continues to lead to benefits for patients.
Mycobacterium liflandii Outbreak in a Research Colony of Xenopus (Silurana) tropicalis Frogs
Authors: Fremont-Rahl J. J. , Ek C. , Williamson H. R. , Small P. L. C. , Fox J. G. , Muthupalani S.
Published: December 2010

A research colony of Xenopus ( Silurana) tropicalis frogs presented with nodular and ulcerative skin lesions. Additional consistent gross findings included splenomegaly with multiple tan-yellow nodular foci in the spleen and liver of diseased frogs. Copious acid-fast positive bacteria were present in touch impression smears of spleen, skin, and livers of diseased frogs. Histologically, necrotizing and granulomatous dermatitis, splenitis, and hepatitis with numerous acid-fast bacilli were consistently present, indicative of systemic mycobacteriosis. Infrequently, granulomatous inflammation was noted in the lungs, pancreas, coelomic membranes, and rarely reproductive organs. Ultrastructurally, both extracellular bacilli and intracellular bacilli within macrophages were identified. Frogs in the affected room were systematically depopulated, and control measures were initiated. Cultured mycobacteria from affected organs were identified and genetically characterized as Mycobacterium liflandii by polymerase chain reaction amplification of the enoyl reductase domain and specific variable numbers of tandem repeats. In recent years, M. liflandii has had a devastating impact on research frog colonies throughout the United States. This detailed report with ultrastructural description of M. liflandii aids in further understanding of this serious disease in frogs.
Coal, Identity, and the Gendering of Environmental Justice Activism in Central Appalachia
Authors: Bell Shannon Elizabeth , Braun Yvonne A.
Published: December 2010

Women generally initiate, lead, and constitute the rank and file of environmental justice activism. However, there is little research on why there are comparatively so few men involved in these movements. Using the environmental justice movement in the Central Appalachian coalfields as a case study, we examine the ways that environmental justice activism is gendered, with a focus on how women’s and men’s identities both shape and constrain their involvement in gendered ways. The analysis relies on 20 interviews with women and men grassroots activists working for environmental justice in the coalfields of Appalachia. We find that women draw on their identities as “mothers” and “Appalachians” to justify their activism, while the hegemonic masculinity of the region, which is tied to the coal industry, has the opposite effect on men, deterring their movement involvement. We explore the implications of these findings for understanding the relationship of gender to environmental justice activism.
Subversive Property: Reshaping Malleable Spaces of Belonging
Authors: Keenan Sarah
Published: December 2010

Despite a wide field of scholarship critiquing the idea and workings of property, most understandings still centre on the propertied subject. This article spatializes property in order to shift the focus away from the propertied subject and onto the broader networks of relations that interact to form property. It draws on critical geography, phenomenology and empirical socio-legal work to argue that property can be understood as a relationship of belonging that is held up by the surrounding space — a relationship that is not fixed or essential but temporally and spatially contingent. Building on Davina Cooper’s analysis of ‘property practices’, I argue that when analysed spatially, the two types of belonging she discusses — belonging between a subject and an object and between a part and a whole — become indistinguishable. As such, characteristics generally associated with identity politics can be understood as property in the same way that owning an object can — in terms of belonging in space. This spatialized understanding shows the breadth of property’s political potential. Although property tends to be (re)productive of the status quo, it can also be subversive. Property can unsettle spaces too.
Financial Development and Economic Growth in India
Authors: Chakraborty Indrani
Published: December 2010

This article examines the impact of the developments in the financial sector on economic growth in India in the post-reform period. The model of Mankiw et al. (1992) was extended to establish a relationship between financial development and economic growth. The model was then estimated using quarterly data for the period 1993 to 2005 for India, using the techniques of cointegration and vector error correction method. Cointegration results show that capital–output ratio and rate of growth of human capital have positive effects on real rate of growth of GDP, irrespective of the indicator of stock market development. An increase in the market capitalization dampens economic growth, whereas turnover has no significant effect, and an increase in the money market rate of interest has a positive effect on economic growth. Real wealth, debt burden, real effective exchange rate and the rate of growth of labour have negative effects. Vector error correction method shows that the ECM term relating to market capitalization and inflation help adjust short-run dynamics of economic growth when we use market capitalization as the indicator of the stock market development. The findings lend no support to the theoretical prediction that the stock market development would play an important role in enhancing economic growth in India. On the contrary, reform measures on the market rate of interest that were introduced in the Indian banking system appear to have promoted economic growth significantly.
Deregulation of TWIST-1 in the CD34+ compartment represents a novel prognostic factor in chronic myeloid leukemia
Authors: Cosset Erika , Hamdan Ghassan , Jeanpierre Sandrine , Voeltzel Thibault , Sagorny Karen , Hayette Sandrine , Mahon François-Xavier , Dumontet Charles , Puisieux Alain , Nicolini Franck E. , Maguer-Satta Véronique
Published: December 2010

The mechanisms of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) often remain obscure. Analysis of patient samples during disease progression revealed the up-regulation of the oncogene TWIST-1, also measured in primary samples from TKI-resistant patients. Moreover, we found that TWIST-1 was overexpressed in CML diagnostic samples of patients who later developed cytogenetic resistance to imatinib, even those without any detectable resistance mechanism. We confirmed the up-regulation of TWIST-1 at both RNA and protein levels in imatinib-resistant cell lines, irrespective of any other resistance mechanism. Analysis with specific small interfering RNA suggested TWIST-1 involvement in the resistance phenotype. Finally, the kinetics of TWIST-1 expression during the individual medical histories of CML patients indicated that TWIST-1 expression is down-regulated by TKIs and up-regulated with TKI resistance. We hypothesize that the overexpression of the TWIST-1 oncogene represents a novel key prognostic factor potentially useful for optimizing CML management in the TKI era.
Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells
Authors: Kanada Shunsuke , Nishiyama Chiharu , Nakano Nobuhiro , Suzuki Ryuyo , Maeda Keiko , Hara Mutsuko , Kitamura Nao , Ogawa Hideoki , Okumura Ko
Published: December 2010

In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow–derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow–derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow–derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cytokines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases.
SYK regulates B-cell migration by phosphorylation of the F-actin interacting protein SWAP-70
Authors: Pearce Glen , Audzevich Tatsiana , Jessberger Rolf
Published: December 2010

B-cell migration into and within lymphoid tissues is not only central to the humoral immune response but also for the development of malignancies and autoimmunity. We previously demonstrated that SWAP-70, an F-actin-binding, Rho GTPase-interacting protein strongly expressed in activated B cells, is necessary for normal B-cell migration in vivo. SWAP-70 regulates integrin-mediated adhesion and cell attachment. Here we show that upon B-cell activation, SWAP-70 is extensively posttranslationally modified and becomes tyrosine phosphorylated by SYK at position 517. This phosphorylation inhibits binding of SWAP-70 to F-actin. Phospho-site mutants of SWAP-70 disrupt B-cell polarization in a dominant-negative fashion in vitro and impair migration in vivo. After CXCL12 stimulation of B cells SYK becomes activated and SWAP-70 is phosphorylated in a SYK-dependent manner. Use of the highly specific SYK inhibitor BAY61-3606 showed SYK activity is necessary for normal chemotaxis and B-cell polarization in vitro and for entry of B cells into lymph nodes in vivo. These findings demonstrate a novel requirement for SYK in migration and polarization of naive recirculating B cells and show that SWAP-70 is an important target of SYK in this pathway.
When a gold standard is made of tin
Authors: Schiller Gary J.
Published: December 2010

In this issue of Blood, Kantarjian and colleagues analyze the outcome of intensive, cytarabine-based induction chemotherapy in the management of elderly patients with newly diagnosed AML treated over an 18-year period, and challenge whether standard, available therapy should ever be offered to a vulnerable population of patients with both adverse clinical- and disease-related characteristics.1
Double-hit B-cell lymphomas
Authors: Aukema Sietse M. , Siebert Reiner , Schuuring Ed , van Imhoff Gustaaf W. , Kluin-Nelemans Hanneke C. , Boerma Evert-Jan , Kluin Philip M.
Published: December 2010

In many B-cell lymphomas, chromosomal translocations are biologic and diagnostic hallmarks of disease. An intriguing subset is formed by the so-called double- hit (DH) lymphomas that are defined by a chromosomal breakpoint affecting the MYC/8q24 locus in combination with another recurrent breakpoint, mainly a t(14;18)(q32;q21) involving BCL2. Recently, these lymphomas have received increased attention, which contributed to the introduction of a novel category of lymphomas in the 2008 WHO classification, “B cell lymphoma unclassifiable with features intermediate between DLBCL and BL.” In this review we explore the existing literature for the most recurrent types of DH B-cell lymphomas and the involved genes with their functions, as well as their pathology and clinical aspects including therapy and prognosis. The incidence of aggressive B-cell lymphomas other than Burkitt lymphoma with a MYC breakpoint and in particular a double hit is difficult to assess, because screening by methods like FISH has not been applied on large, unselected series, and the published cytogenetic data may be biased to specific categories of lymphomas. DH lymphomas have been classified heterogeneously but mostly as DLBCL, the majority having a germinal center phenotype and expression of BCL2. Patients with DH lymphomas often present with poor prognostic parameters, including elevated LDH, bone marrow and CNS involvement, and a high IPI score. All studies on larger series of patients suggest a poor prognosis, also if treated with RCHOP or high-intensity treatment modalities. Importantly, this poor outcome cannot be accounted for by the mere presence of a MYC/8q24 breakpoint. Likely, the combination of MYC and BCL2 expression and/or a related high genomic complexity are more important. Compared to these DH lymphomas, BCL6+/MYC+ DH lymphomas are far less common, and in fact most of these cases represent BCL2+/BCL6+/MYC+ triple-hit lymphomas with involvement of BCL2 as well. CCND1+/MYC+ DH lymphomas with involvement of 11q13 may also be relatively frequent, the great majority being classified as aggressive variants of mantle cell lymphoma. This suggests that activation of MYC might be an important progression pathway in mantle cell lymphoma as well. Based on clinical significance and the fact that no other solid diagnostic tools are available to identify DH lymphomas, it seems advisable to test all diffuse large B-cell and related lymphomas for MYC and other breakpoints.
ITP: Tregs come to the rescue
Authors: Chong Beng H.
Published: December 2010

In this issue of Blood, Bao et al report an increase in regulatory T-cell activity in patients with ITP treated with thrombopoietin receptor (TPO-R) agonists.1 This finding implies that TPO-R agonists may have an unexpected immune-regulatory activity. If this is indeed the case, the mechanism by which TPO-R agonists could perform such a function is currently unclear.
Challenges and perspectives for improved management of HIV/Mycobacterium tuberculosisco-infection
Authors: Sester M. , Giehl C. , McNerney R. , Kampmann B. , Walzl G. , Cuchí P. , Wingfield C. , Lange C. , Migliori G.B. , Kritski A.L. , Meyerhans A.
Published: December 2010

HIV andMycobacterium tuberculosis(MTB) are two widespread and highly successful microbes whose synergy in pathogenesis has created a significant threat for human health globally. In acknowledgement of this fact, the European Union (EU) has funded a multinational support action, the European Network for global cooperation in the field of AIDS and TB (EUCO-Net), that brings together experts from Europe and those regions that bear the highest burden of HIV/MTB co-infection. Here, we summarise the main outcome of the EUCO-Net project derived from an expert group meeting that took place in Stellenbosch (South Africa) (AIDS/TB Workshop on Research Challenges and Opportunities for Future Collaboration) and the subsequent discussions, and propose priority areas for research and concerted actions that will have impact on future EU calls.
The use of thoracic computed tomography scanning and EBUS-TBNA to diagnose tuberculosis of the central nervous system: two case reports
Authors: Mehta M.R. , Connell D.W. , Wickremasinghe M.I. , Kon O.M.
Published: December 2010

Herein, we report two cases of tuberculosis (TB) of the central nervous system where accessing the cerebrospinal fluid for diagnostic purposes was relatively or absolutely contraindicated at presentation.

The finding of mediastinal lymphadenopathy on thoracic computed tomography scans, which was not visible on plain chest radiography, allowed endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of these lymph nodes to support the diagnosis of TB in each patient and rule out other disease processes.

EBUS-TBNA is a new bronchoscopic technique and in this case report appears to be a safe and useful option in the diagnosis of TB. Moreover, it proved to be so in cases where the main focus of disease was outside the thorax.
The role of echocardiography in the diagnosis and management of patients with pulmonary hypertension
Authors: Habib G. , Torbicki A.
Published: December 2010

Pulmonary hypertension (PH) is defined as an increased mean pulmonary artery pressure (P̄pa) >25 mmHg at rest as assessed by right heart catheterisation (RHC). However, this technique is invasive and noninvasive alternatives are desirable for early diagnosis of PH. Although estimation of systolic pulmonary arterial pressure is easily obtained using Doppler echocardiography, cases of under- and over-estimations are not rare and direct measurement ofP̄pais not possible using this method. Therefore, echocardiography should be considered as a tool for assessment of the likelihood rather than the definite presence or absence of PH. Transthoracic echocardiography may be useful for noninvasive screening of patients at risk of PH. On the basis of an echocardiographic assessment, patients showing signs suggestive of PH can be referred for a confirmatory RHC. A number of variables measured during echocardiography reflect the morphological and functional consequences of PH and have prognostic value. The presence of pericardial effusion, reduced tricuspid annular plane excursion and right atrial enlargement are associated with a poorer prognosis. Echocardiography is also an important procedure for monitoring the response of patients to therapy, and is recommended 3−4 months after initiation of, or a change in, therapy. Echocardiographic assessment as part of a goal-oriented approach to therapy is essential for the effective management of PH patients.
Treat-to-target strategies in pulmonary arterial hypertension: the importance of using multiple goals
Authors: Sitbon O. , Galiè N.
Published: December 2010

Major advances have occurred in the treatment of pulmonary arterial hypertension (PAH) over the past decade. The advent of PAH-specific pharmacological treatments has offered hope to patients with a debilitating, progressive disease and a poor prognosis. Combined drug treatment offers improved benefits over monotherapy, and current treatment guidelines for PAH recommend a sequential add-on approach to combination therapy for patients in New York Heart Association (NYHA)/World Health Organization functional class (WHO FC) II–IV.

Goal-oriented therapy determines the timing of treatment escalation by inadequate response to known prognostic indicators. Close monitoring of patients aids the early identification of inadequate response, so that treatment can be escalated promptly and before the patient's condition deteriorates further. Existing treatment goals are based on baseline values of prognostic indicators, but it is vital to identify risk factors that are both relevant during treatment and that can be assessed during follow-up appointments. Data from different PAH aetiologies indicate that NYHA/WHO FC is the most appropriate prognostic marker, with 6-min walk distance and several haemodynamic parameters representing alternatives.

Future refinement of goal-oriented therapy could include the use of multiple prognostic markers, while additional, large clinical trials will answer questions concerning choice and combination of treatment goals.
Issues related to the management and therapy of paediatric pulmonary hypertension
Authors: Schulze-Neick I. , Beghetti M.
Published: December 2010

An increasing number of medical services dedicated to the diagnosis, treatment and follow-up of pulmonary hypertension (PH) in children are being established. This has, in turn, increased the need to adapt current guidelines for the treatment of PH to be more relevant to paediatric patients with PH. This article will summarise the data obtained so far from paediatric registries, national cohorts and clinical trials and discuss the best approach for developing a treatment algorithm designed for children with different types of PH. The many unanswered questions, challenges and issues relating to the PH in the paediatric population will also be discussed.
High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5
Authors: Ching Yung-Hao , Munroe Robert J , Moran Jennifer L , Barker Anna K , Mauceli Evan , Fennell Tim , diPalma Frederica , Lindblad-Toh Kerstin , Abcunas Lindsay M , Gilmour Joyanna F , Harris Tanya P , Kloet Susan L , Luo Yunhai , McElwee John L , Mu Weipeng , Park Hyo K , Rogal David L , Schimenti Kerry J , Shen Lishuang , Shindo Mami , Shou James Y , Stenson Erin K , Stover Patrick J , Schimenti John C
Published: December 2010

Background

Forward genetic screens in mice provide an unbiased means to identify genes and other functional genetic elements in the genome. Previously, a large scale ENU mutagenesis screen was conducted to query the functional content of a ~50 Mb region of the mouse genome on proximal Chr 5. The majority of phenotypic mutants recovered were embryonic lethals.

Results

We report the high resolution genetic mapping, complementation analyses, and positional cloning of mutations in the target region. The collection of identified alleles include several with known or presumed functions for which no mutant models have been reported (Tbc1d14, Nol14, Tyms, Cad, Fbxl5, Haus3), and mutations in genes we or others previously reported (Tapt1, Rest, Ugdh, Paxip1, Hmx1, Otoe, Nsun7). We also confirmed the causative nature of a homeotic mutation with a targeted allele, mapped a lethal mutation to a large gene desert, and localized a spermiogenesis mutation to a region in which no annotated genes have coding mutations. The mutation in Tbc1d14 provides the first implication of a critical developmental role for RAB-GAP-mediated protein transport in early embryogenesis.

Conclusion

This collection of alleles contributes to the goal of assigning biological functions to all known genes, as well as identifying novel functional elements that would be missed by reverse genetic approaches.