bluuebunny/crossref_metadata_2025 huggingface dataset:
Space–wavenumber and time–frequency analysis for damage inspection of thin-walled structures
Authors: Pai P. Frank , Sundaresan Mannur J.
Published: February 2012

This article presents a dynamics-based methodology for accurate damage inspection of thin-walled structures by combining a boundary effect evaluation method (BEEM) for space–wavenumber analysis of measured operational deflection shapes (ODSs) and a conjugate-pair decomposition (CPD) method for time–frequency analysis of time traces of measured points. BEEM is for locating and estimating small structural damages by processing ODSs measured by a full-field measurement system (e.g. a scanning laser vibrometer or a camera-based motion measurement system). BEEM is a nondestructive spatial domain method based on sliding-window processing of ODSs, and it works without using any structural model or historical data for comparison. Similar to the short-time Fourier transform and wavelet transform, CPD uses adaptive windowed regular harmonics and function orthogonality to perform time–frequency analysis of time traces by extracting time-localized regular and/or distorted harmonics. Both BEEM and CPD are local spectral analyses based on local, adaptive curve fitting. The first estimation of the wavenumber for BEEM and the frequency for CPD is obtained using a four-point Teager–Kaiser algorithm based on the use of finite difference. Numerical simulations and experimental results show that the combination of BEEM and CPD for space–wavenumber and time–frequency analyses provide an accurate tool for damage inspection of thin-walled structures.
Long-term benefits of online risk-based direct-current optimal power flow
Authors: Dai R-C , Pham H , Wang Y , McCalley J D
Published: February 2012

An online operational risk management method is presented in this paper. In this method, a risk-based direct-current (DC) optimal power flow approach is utilized to replace a traditional security-constrained DC optimal power flow approach. This risk management method is integrated into a commercial energy management system/dispatcher training simulator system to monitor and control system operation risk online. Comparison of the approach with traditional security assessment shows significant benefits over the long term via cost reduction and risk mitigation. A case study provides supporting evidence of risk mitigation in terms of steady-state angular separation reduction and cascading prevention.
F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation
Authors: Chen Bill B. , Glasser Jennifer R. , Coon Tiffany A. , Zou Chunbin , Miller Hannah L. , Fenton Moon , McDyer John F. , Boyiadzis Michael , Mallampalli Rama K.
Published: February 2012

Hematologic maligancies exhibit a growth advantage by up-regulation of components within the molecular apparatus involved in cell-cycle progression. The SCF (Skip-Cullin1-F-box protein) E3 ligase family provides homeostatic feedback control of cell division by mediating ubiquitination and degradation of cell-cycle proteins. By screening several previously undescribed E3 ligase components, we describe the behavior of a relatively new SCF subunit, termed FBXL2, that ubiquitinates and destabilizes cyclin D2 protein leading to G0 phase arrest and apoptosis in leukemic and B-lymphoblastoid cell lines. FBXL2 expression was strongly suppressed, and yet cyclin D2 protein levels were robustly expressed in acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) patient samples. Depletion of endogenous FBXL2 stabilized cyclin D2 levels, whereas ectopically expressed FBXL2 decreased cyclin D2 lifespan. FBXL2 did not bind a phosphodegron within its substrate, which is typical of other F-box proteins, but uniquely targeted a calmodulin-binding signature within cyclin D2 to facilitate its polyubiquitination. Calmodulin competes with the F-box protein for access to this motif where it bound and protected cyclin D2 from FBXL2. Calmodulin reversed FBXL2-induced G0 phase arrest and attenuated FBXL2-induced apoptosis of lymphoblastoid cells. These results suggest an antiproliferative effect of SCFFBXL2 in lymphoproliferative malignancies.
Tim-3 is an inducible human natural killer cell receptor that enhances interferon gamma production in response to galectin-9
Authors: Gleason Michelle K. , Lenvik Todd R. , McCullar Valarie , Felices Martin , O'Brien M. Shea , Cooley Sarah A. , Verneris Michael R. , Cichocki Frank , Holman Carol J. , Panoskaltsis-Mortari Angela , Niki Toshiro , Hirashima Mitsuomi , Blazar Bruce R. , Miller Jeffrey S.
Published: February 2012

NK-cell function is regulated by the integration of signals received from activating and inhibitory receptors. Here we show that a novel immune receptor, T-cell Ig and mucin-containing domain-3 (Tim-3), is expressed on resting human NK cells and is up-regulated on activation. The NK92 NK-cell line engineered to overexpress Tim-3 showed a marked increase in IFN-γ production in the presence of soluble rhGal-9 or Raji tumor cells engineered to express Gal-9. The Tim-3+ population of low-dose IL-12/IL-18–activated primary NK cells significantly increased IFN-γ production in response to soluble rhGal-9, Gal-9 presented by cell lines, and primary acute myelogenous leukemia (AML) targets that endogenously express Gal-9. This effect is highly specific as Tim-3 Ab blockade significantly decreased IFN-γ production, and Tim-3 cross-linking induced ERK activation and degradation of IκBα. Exposure to Gal-9–expressing target cells had little effect on CD107a degranulation. Reconstituted NK cells obtained from patients after hematopoietic cell transplantation had diminished expression of Tim-3 compared with paired donors. This observation correlates with the known IFN-γ defect seen early posttransplantation. In conclusion, we show that Tim-3 functions as a human NK-cell coreceptor to enhance IFN-γ production, which has important implications for control of infectious disease and cancer.
Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma
Authors: Nishikawa Hiroyoshi , Maeda Yuka , Ishida Takashi , Gnjatic Sacha , Sato Eiichi , Mori Fumiko , Sugiyama Daisuke , Ito Asahi , Fukumori Yasuo , Utsunomiya Atae , Inagaki Hiroshi , Old Lloyd J. , Ueda Ryuzo , Sakaguchi Shimon
Published: February 2012

Adult T-cell leukemia/lymphoma (ATLL) is an intractable hematologic malignancy caused by human T-lymphotropic virus type 1 (HTLV-1), which infects approximately 20 million people worldwide. Here, we have explored the possible expression of cancer/testis (CT) antigens by ATLL cells, as CT antigens are widely recognized as ideal targets of cancer immunotherapy against solid tumors. A high percentage (87.7%) of ATLL cases (n = 57) expressed CT antigens at the mRNA level: NY-ESO-1 (61.4%), MAGE-A3 (31.6%), and MAGE-A4 (61.4%). CT antigen expression was confirmed by immunohistochemistry. This contrasts with other types of lymphoma or leukemia, which scarcely express these CT antigens. Humoral immune responses, particularly against NY-ESO-1, were detected in 11.6% (5 of 43) and NY-ESO-1–specific CD8+ T-cell responses were observed in 55.6% (5 of 9) of ATLL patients. NY-ESO-1–specific CD8+ T cells recognized autologous ATLL cells and produced effector cytokines. Thus, ATLL cells characteristically express CT antigens and therefore vaccination with CT antigens can be an effective immunotherapy of ATLL.
Leukotriene C4 induces migration of human monocyte–derived dendritic cells without loss of immunostimulatory function
Authors: Dannull Jens , Schneider Tristan , Lee Walter T. , de Rosa Nicole , Tyler Douglas S. , Pruitt Scott K.
Published: February 2012

Generation of human monocyte–derived dendritic cells (DCs) for cancer vaccination involves ex vivo maturation in the presence of proinflammatory cytokines and prostaglandin E(2) (PGE2). Although the inclusion of PGE2 during maturation is imperative for the induction of DC migration, PGE2 has unfavorable effects on the immunostimulatory capacity of these cells. Like PGE2, leukotrienes (LTs) are potent mediators of DC migration. We therefore sought to characterize the migratory and immunologic properties of DCs that matured in the presence of LTB4, LTC4, LTD4, and PGE2. Here, we demonstrate that DCs matured in the presence of LTC4, but not LTB4 or LTD4, are superior to PGE2-matured DCs in stimulating CD4+ T-cell responses and in inducing antigen-specific cytotoxic T lymphocytes (CTLs) in vitro without concomitant induction or recruitment of regulatory T cells (Tregs). LTC4-matured DCs migrate efficiently through layers of extracellular matrix and secrete higher levels of immunostimulatory IL-12p70 while producing reduced levels of immune-inhibitory IL-10, IL12p40, indoleamine-2,3-dioxidase, and TIMP-1 (tissue inhibitor of matrix metalloproteinases). Intracellular calcium mobilization and receptor antagonist studies reveal that, in contrast to LTD4, LTC4 did not signal through CysLTR1 in DCs. Collectively, our data suggest that LTC4 represents a promising candidate to replace PGE2 in DC maturation protocols for cancer vaccination.
Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?
Authors: Hasselbalch Hans Carl
Published: February 2012

The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because of myelofibrosis and leukemic transformation. In the general population, chronic inflammation is considered of major importance for the development of atherosclerosis and cancer. MPNs are characterized by a state of chronic inflammation, which is proposed to be the common denominator for the development of “premature atherosclerosis,” clonal evolution, and second cancer in patients with MPNs. Chronic inflammation may both initiate clonal evolution and catalyze its expansion from early disease stage to the myelofibrotic burnt-out phase. Furthermore, chronic inflammation may also add to the severity of cardiovascular disease burden by accelerating the development of atherosclerosis, which is well described and recognized in other chronic inflammatory diseases. A link between chronic inflammation, atherosclerosis, and second cancer in MPNs favors early intervention at the time of diagnosis (statins and interferon-α2), the aims being to dampen chronic inflammation and clonal evolution and thereby also diminish concurrent disease-mediated chronic inflammation and its consequences (accelerated atherosclerosis and second cancer).
Cervical cancer cell lines expressing NKG2D-ligands are able to down-modulate the NKG2D receptor on NKL cells with functional implications
Authors: Jimenez-Perez Miriam I , Jave-Suarez Luis F , Ortiz-Lazareno Pablo C , Bravo-Cuellar Alejandro , Gonzalez-Ramella Oscar , Aguilar-Lemarroy Adriana , Hernandez-Flores Georgina , Pereira-Suarez Ana L , Daneri-Navarro Adrian , del Toro-Arreola Susana
Published: February 2012

Background

Cervical cancer represents the third most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women worldwide. Natural killer (NK) cells play an important role in the defense against viruses, intracellular bacteria and tumors. NKG2D, an activating receptor on NK cells, recognizes MHC class I chain-related molecules, such as MICA/B and members of the ULBP/RAET1 family. Tumor-derived soluble NKG2D-ligands have been shown to down-modulate the expression of NKG2D on NK cells. In addition to the down-modulation induced by soluble NKG2D-ligands, it has recently been described that persistent cell-cell contact can also down-modulate NKG2D expression. The goal of this study was to determine whether the NKG2D receptor is down-modulated by cell-cell contact with cervical cancer cells and whether this down-modulation might be associated with changes in NK cell activity.

Results

We demonstrate that NKG2D expressed on NKL cells is down-modulated by direct cell contact with cervical cancer cell lines HeLa, SiHa, and C33A, but not with non-tumorigenic keratinocytes (HaCaT). Moreover, this down-modulation had functional implications. We found expression of NKG2D-ligands in all cervical cancer cell lines, but the patterns of ligand distribution were different in each cell line. Cervical cancer cell lines co-cultured with NKL cells or fresh NK cells induced a marked diminution of NKG2D expression on NKL cells. Additionally, the cytotoxic activity of NKL cells against K562 targets was compromised after co-culture with HeLa and SiHa cells, while co-culture with C33A increased the cytotoxic activity of the NKL cells.

Conclusions

Our results suggest that differential expression of NKG2D-ligands in cervical cancer cell lines might be associated with the down-modulation of NKG2D, as well as with changes in the cytotoxic activity of NKL cells after cell-cell contact with the tumor cells.
A comparison of two distinct murine macrophage gene expression profiles in response to Leishmania amazonensisinfection
Authors: Probst Christian M , Silva Rodrigo A , B Menezes Juliana P , Almeida Tais F , Gomes Ivana N , Dallabona Andréia C , Ozaki Luiz S , Buck Gregory A , Pavoni Daniela P , Krieger Marco A , T Veras Patrícia S
Published: February 2012

Background

The experimental murine model of leishmaniasis has been widely used to characterize the immune response againstLeishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions underL. amazonensisinfection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and afterL. amazonensisinfection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite.

Results

The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as cell function. Uninfected C57BL/6 macrophages express genes involved in the deactivation pathway of macrophages at lower levels, while genes related to the activation of the host immune inflammatory response, including apoptosis and phagocytosis, have elevated expression levels. Several genes that participate in the apoptosis process were also observed to be up-regulated in C57BL/6 macrophages infected withL. amazonensis, which is very likely related to the capacity of these cells to control parasite infection. By contrast, genes involved in lipid metabolism were found to be up-regulated in CBA macrophages in response to infection, which supports the notion thatL. amazonensisprobably modulates parasitophorous vacuoles in order to survive and multiply in host cells.

Conclusion

The transcriptomic profiles of C57BL/6 macrophages, before and after infection, were shown to be involved in the macrophage pathway of activation, which may aid in the control ofL. amazonensisinfection, in contrast to the profiles of CBA cells.
A placebo-controlled trial of Korean red ginseng extract for preventing Influenza-like illness in healthy adults
Authors: Ha Ki-Chan , Kim Min-Gul , Oh Mi-Ra , Choi Eun-Kyung , Back Hyang-Im , Kim Sun-Young , Park Eun-Ok , Kwon Dae-Young , Yang Hye-Jeong , Kim Min-Jeong , Kang Hee-Joo , Lee Ju-Hyung , Choi Kyung-Min , Chae Soo-Wan , Lee Chang-Seop
Published: February 2012

Abstracts

Background

Standardized Korean red ginseng extract has become the best-selling influenza-like illness (ILI) remedy in Korea, yet much controversy regarding the efficacy of the Korean red ginseng (KRG) in reducing ILI incidence remains. The aim of the study is to assess the efficacy of the KRG extract on the ILI incidence in healthy adults.

Methods/Design

We will conduct a randomized, double-blind, placebo-controlled study at the onset of the influenza seasons. A total of 100 subjects 30-70 years of age will be recruited from the general populations. The subjects will be instructed to take 9 capsules per day of either the KRG extract or a placebo for a period of 3 months. The primary outcome measure is to assess the frequency of ILI onset in participated subjects. Secondary variable measures will be included severity and duration of ILI symptoms. The ILI symptoms will be scored by subjects using a 4-point scale.

Discussion

This study is a randomized placebo controlled trial to evaluate the efficacy of the KRG extract compared to placebo and will be provided valuable new information about the clinical and physiological effects of the KRG extract on reduction of ILI incidence including flu and upper respiratory tract infections. The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if KRG extract can be shown to be an effective reduction strategy in ILI incidence.

Trial Registration

NCT01478009.
Secreted protein acidic and rich in cysteine (SPARC) is associated with nasopharyngeal carcinoma metastasis and poor prognosis
Authors: Wang Hai-Yun , Li Yang-Yang , Shao Qiong , Hou Jing-Hui , Wang Fang , Cai Man-Bo , Zeng Yi-Xin , Shao Jian-Yong
Published: February 2012

Background

The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC) in nasopharyngeal carcinoma (NPC) specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC

Methods

NPC tissue microarrays (TMAs) were constructed from Sun Yat-sen University Cancer Center (SYSUCC), another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs) induced by Bmi-1 (NPEC2 Bmi-1). The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models.

Results

The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001). SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium.

In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001) and WHO histological classification (P = 0.023). NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P < 0.001), especially patients with advanced stage disease (log-rank, P < 0.001). Multivariate analysis suggested that the level of SPARC expression was an independent prognostic indicator for the overall survival of patients with NPC (P < 0.001).

Conclusions

SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.
Recommended number of strides for automatic assessment of gait symmetry and regularity in above-knee amputees by means of accelerometry and autocorrelation analysis
Authors: Tura Andrea , Rocchi Laura , Raggi Michele , Cutti Andrea G , Chiari Lorenzo
Published: February 2012

Background

Symmetry and regularity of gait are essential outcomes of gait retraining programs, especially in lower-limb amputees. This study aims presenting an algorithm to automatically compute symmetry and regularity indices, and assessing the minimum number of strides for appropriate evaluation of gait symmetry and regularity through autocorrelation of acceleration signals.

Methods

Ten transfemoral amputees (AMP) and ten control subjects (CTRL) were studied. Subjects wore an accelerometer and were asked to walk for 70 m at their natural speed (twice). Reference values of step and stride regularity indices (Ad1 and Ad2) were obtained by autocorrelation analysis of the vertical and antero-posterior acceleration signals, excluding initial and final strides. The Ad1 and Ad2 coefficients were then computed at different stages by analyzing increasing portions of the signals (considering both the signals cleaned by initial and final strides, and the whole signals). At each stage, the difference between Ad1 and Ad2 values and the corresponding reference values were compared with the minimum detectable difference, MDD, of the index. If that difference was less than MDD, it was assumed that the portion of signal used in the analysis was of sufficient length to allow reliable estimation of the autocorrelation coefficient.

Results

All Ad1 and Ad2 indices were lower in AMP than in CTRL (P < 0.0001). Excluding initial and final strides from the analysis, the minimum number of strides needed for reliable computation of step symmetry and stride regularity was about 2.2 and 3.5, respectively. Analyzing the whole signals, the minimum number of strides increased to about 15 and 20, respectively.

Conclusions

Without the need to identify and eliminate the phases of gait initiation and termination, twenty strides can provide a reasonable amount of information to reliably estimate gait regularity in transfemoral amputees.
Generalized anxiety modulates frontal and limbic activation in major depression
Authors: Schlund Michael W , Verduzco Guillermo , Cataldo Michael F , Hoehn-Saric Rudolf
Published: February 2012

Background

Anxiety is relatively common in depression and capable of modifying the severity and course of depression. Yet our understanding of how anxiety modulates frontal and limbic activation in depression is limited.

Methods

We used functional magnetic resonance imaging and two emotional information processing tasks to examine frontal and limbic activation in ten patients with major depression and comorbid with preceding generalized anxiety (MDD/GAD) and ten non-depressed controls.

Results

Consistent with prior studies on depression, MDD/GAD patients showed hypoactivation in medial and middle frontal regions, as well as in the anterior cingulate, cingulate and insula. However, heightened anxiety in MDD/GAD patients was associated with increased activation in middle frontal regions and the insula and the effects varied with the type of emotional information presented.

Conclusions

Our findings highlight frontal and limbic hypoactivation in patients with depression and comorbid anxiety and indicate that anxiety level may modulate frontal and limbic activation depending upon the emotional context. One implication of this finding is that divergent findings reported in the imaging literature on depression could reflect modulation of activation by anxiety level in response to different types of emotional information.
APC/C-Cdh1-dependent anaphase and telophase progression during mitotic slippage
Authors: Toda Kazuhiro , Naito Kayoko , Mase Satoru , Ueno Masaru , Uritani Masahiro , Yamamoto Ayumu , Ushimaru Takashi
Published: February 2012

Background

The spindle assembly checkpoint (SAC) inhibits anaphase progression in the presence of insufficient kinetochore-microtubule attachments, but cells can eventually override mitotic arrest by a process known as mitotic slippage or adaptation. This is a problem for cancer chemotherapy using microtubule poisons.

Results

Here we describe mitotic slippage in yeast bub2Δ mutant cells that are defective in the repression of precocious telophase onset (mitotic exit). Precocious activation of anaphase promoting complex/cyclosome (APC/C)-Cdh1 caused mitotic slippage in the presence of nocodazole, while the SAC was still active. APC/C-Cdh1, but not APC/C-Cdc20, triggered anaphase progression (securin degradation, separase-mediated cohesin cleavage, sister-chromatid separation and chromosome missegregation), in addition to telophase onset (mitotic exit), during mitotic slippage. This demonstrates that an inhibitory system not only of APC/C-Cdc20 but also of APC/C-Cdh1 is critical for accurate chromosome segregation in the presence of insufficient kinetochore-microtubule attachments.

Conclusions

The sequential activation of APC/C-Cdc20 to APC/C-Cdh1 during mitosis is central to accurate mitosis. Precocious activation of APC/C-Cdh1 in metaphase (pre-anaphase) causes mitotic slippage in SAC-activated cells. For the prevention of mitotic slippage, concomitant inhibition of APC/C-Cdh1 may be effective for tumor therapy with mitotic spindle poisons in humans.
Overexpression of DNA damage-induced 45 α gene contributes to esophageal squamous cell cancer by promoter hypomethylation
Authors: Wang Bao xiang , Yin Bang Liang , He Bin , Chen Chen , Zhao Ming , Zhang Wei xing , Xia Zhen Kun , Pan Yi zhi , Tang Jing qun , Zhou Xin min , Yin Ni
Published: February 2012

Background

Environmental factors-induced dysfunction of esophageal squamous epithelium, including genomic DNA impairment and apoptosis, play an important role in the pathogenesis of esophageal squamous cell cancer. DNA damage-induced 45α (GADD45α) has been found promoting DNA repair and removing methylation marker, Therefore, in this study we will investigate whether GADD45α expression is induced and its mechanism in esophageal squamous cell cancer.

Methods

Two human esophageal squamous cell lines (ESCC), ECA109 and KYSE510 were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS). Lipofectamine 2000 was used to transfect cells. mRNA level of GADD45α was measured by reverse transcription-quantitive PCR (RT-qPCR), protein level of GADD45α was detected by western blot and Immunohistochemistry. Global DNA methylation of tissue sample was measured using the Methylamp Global DNA Methylation Quantification Ultra kit (Epigentek Group) and promoter methylation was measured by bisulfite sequencing.

Results

GADD45a mRNA and protein levels were increased significantly in tumor tissue than that in adjacent normal tissue. Hypomethylation of global genomic DNA and GADD45α promoter were found in ESCC. The cell sensitivity to Cisplatin DDP was decreased significantly in Eca109 and Kyse510 cells, in which GADD45α expression was down-regulated by RNA interference (RNAi). In addition, silence of GADD45a expression in ESCC cells inhibited proliferation and promoted apoptosis.

Conclusion

Overexpression of GADD45α gene is due to DNA hypomethylation in ESCC. GADD45α may be a protective factor in DDP chemotherapy for esophageal squamous cell carcinoma.
Nocturnal heart rate variability parameters as potential fibromyalgia biomarker: correlation with symptoms severity
Authors: Lerma Claudia , Martinez Aline , Ruiz Natllely , Vargas Angelica , Infante Oscar , Martinez-Lavin Manuel
Published: February 2012

Introduction

At present, there is neither a laboratory test nor an imaging technique able to differentiate people with fibromyalgia (FM) from healthy controls. This lack of an objective biomarker has hampered FM recognition and research. Heart rate variability (HRV) analyses provide a quantitative marker of autonomic nervous system activity. Nighttime is a stable period in which most people are resting. Sleep is modulated by autonomic activity. Sleeping problems are prominent in FM. The objectives of this study are: 1) to explore different nocturnal HRV parameters as potential FM biomarkers and 2) to seek correlation between such HRV parameters and diverse FM symptoms.

Methods

We studied 22 women suffering from FM and 22 age-matched controls. All participants filled out several questionnaires related to FM symptoms. All participants used a Holter monitor over 24 hours while undertaking their routine activities during the day and while sleeping at their homes at night. Time-domain HRV parameters analyzed from 0000 to 0600 hours included, among others: mean normal-normal interbeat intervals (mean NN), standard deviation of the NN intervals (SDNN), and standard deviation of the successive NN differences (SDSD).

Results

Nocturnal SDNN of less than 114 ms had the greatest predictive value to set apart patients from controls with an odds ratio of 13.6 (95% confidence interval: 3.9 to 47.8). In patients, decreased nighttime HRV markers indicative of sympathetic predominance had significant correlations with several FM symptoms: SDSD was associated with pain intensity (r = - 0.65, P = 0.001). SDNN correlated with constipation (r = - 0.53, P = 0.001), and mean NN with depression (r = - 0.53, P = 0.001). Controls displayed an opposite behavior. For them, increased nighttime SDNN correlated with Fibromyalgia Impact Questionnaire scores (r = 0.69, P = 0.001) and with other FM symptoms.

Conclusions

Nocturnal HRV indices indicative of sympathetic predominance are significantly different in FM women when compared to healthy individuals. In FM patients, these HRV parameters correlated with several symptoms including pain severity. Opposite associations were seen in controls. FM may not be just one end of a continuous spectrum of common symptoms. Nocturnal HRV analyses are potential FM biomarkers.
CD66b overexpression and homotypic aggregation of human peripheral blood neutrophils after activation by a gram-positive stimulus
Authors: Schmidt Thomas , Zündorf Josef , Grüger Thomas , Brandenburg Kerstin , Reiners Ana-Lena , Zinserling Jörg , Schnitzler Norbert
Published: February 2012

Neutrophils represent the main component of innate immunity in the clearance of bacterial infections. To pass the tissue and to localize and reach the site of infection, the peripheral blood neutrophils have to pass through a complex receptor-mediated interaction with the endothelial layer. Under pathophysiological conditions, such as severe sepsis, this process is impaired and often characterized by neutrophil aggregation. In this study, we examined the impact of three different Staphylococcus aureus strains on the activation status of human peripheral blood neutrophils by coincubation of bacterial culture supernatant with whole blood. This complex interaction of a gram-positive stimulus with blood components leads to a special neutrophil activation phenotype, which is characterized by an overexpression of the cell-surface molecule CD66b. The process is accompanied by a strong increase of homotypic aggregates and seems to be initialized by a massive activation impulse caused by the interplay of plasma components. This maximum activation of neutrophils prior to the complex and highly regulated activation required for transmigration might play a key role in the neutrophil dysfunction in gram-positive sepsis.
Direct Interactions between Calcitonin-Like Receptor (CLR) and CGRP-Receptor Component Protein (RCP) Regulate CGRP Receptor Signaling
Authors: Egea Sophie C. , Dickerson Ian M.
Published: February 2012

Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling.
Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice
Authors: Xu Fen , Burk David , Gao Zhanguo , Yin Jun , Zhang Xia , Weng Jianping , Ye Jianping
Published: February 2012

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.
The role of Hes genes in intestinal development, homeostasis and tumor formation
Authors: Ueo Taro , Imayoshi Itaru , Kobayashi Taeko , Ohtsuka Toshiyuki , Seno Hiroshi , Nakase Hiroshi , Chiba Tsutomu , Kageyama Ryoichiro
Published: February 2012

Notch signaling regulates intestinal development, homeostasis and tumorigenesis, but its precise downstream mechanism remains largely unknown. Here we found that inactivation of the Notch effectors Hes1, Hes3 and Hes5, but not Hes1 alone, led to reduced cell proliferation, increased secretory cell formation and altered intestinal structures in adult mice. However, in Apc mutation-induced intestinal tumors, inactivation of Hes1 alone was sufficient for reducing tumor cell proliferation and inducing differentiation of tumor cells into all types of intestinal epithelial cells, but without affecting the homeostasis of normal crypts owing to genetic redundancy. These results indicated that Hes genes cooperatively regulate intestinal development and homeostasis and raised the possibility that Hes1 is a promising target to induce the differentiation of tumor cells.
Physical gills prevent drowning of many wetland insects, spiders and plants
Authors: Pedersen Ole , Colmer Timothy D.
Published: February 2012

Insects, spiders and plants risk drowning in their wetland habitats. The slow diffusion of O2 can cause asphyxiation when underwater, as O2 supply cannot meet respiratory demands. Some animals and plants have found a common solution to the major challenge: how to breathe underwater with respiratory systems evolved for use in air? Hydrophobic surfaces on their bodies possess gas films that act as a ‘physical gill’ to collect O2 when underwater and thus sustain respiration. In aquatic insects, this feature/process has been termed ‘plastron respiration’. Here, we demonstrate the similarities in function between underwater respiration of insect (Aphelocheirus aestivalis) plastrons and gas films on leaves of wetland plants (Phalaris arundinacea) and also show the importance of these physical gills by the resulting changes upon their removal. The gas films provide an enlarged gas–water interface to enhance O2 uptake underwater that is above that if only spiracles (insects) or stomata (plants) provided the gas-phase contact with the water. Body-surface gas films contribute to the survival of many insects, spiders and plants in aquatic and flood-prone environments.
The Effects of Housing Assistance on Labor Supply: Evidence from a Voucher Lottery
Authors: Jacob Brian A , Ludwig Jens
Published: February 2012

This study estimates the effects of means-tested housing programs on labor supply using data from a randomized housing voucher wait-list lottery in Chicago. Economic theory is ambiguous about the expected sign of any labor supply response. We find that among working-age, able-bodied adults, housing voucher use reduces labor force participation by around 4 percentage points (6 percent) and quarterly earnings by $329 (10 percent), and increases Temporary Assistance for Needy Families program participation by around 2 percentage points (15 percent). We find no evidence that the housing-specific mechanisms hypothesized to promote work, such as neighborhood quality or residential stability, are important empirically. (JEL I38, J22, R23, R38)
Overcoming Adverse Selection: How Public Intervention Can Restore Market Functioning
Authors: Tirole Jean
Published: February 2012

The paper provides a first analysis of market jump starting and its two-way interaction between mechanism design and participation constraints. The government optimally overpays for the legacy assets and cleans up the market of its weakest assets, through a mixture of buybacks and equity injections, and leaves the firms with the strongest legacy assets to the market. The government reduces adverse selection enough to let the market rebound, but not too much, so as to limit the cost of intervention. The existence of a market imposes no welfare cost. (JEL D82, D83, G01, G31, H81)
Assessing the relationship between volume and outcome in hospital services: implications for service centralization
Authors: Harrison Anthony
Published: February 2012

Proposals for centralizing services are often justified on the basis of studies linking the volume of activity to the outcomes achieved. However, the evidence of such studies is far from demonstrating a causal link between volume and outcome. This article assesses the main reasons why volume and outcome studies do not in themselves demonstrate a causal link, and therefore do not provide adequate support for proposals for centralizing hospital services. It then sets out a number of precepts to guide those responsible for proposing centralization of services.
Cartilaginous metaplasia of varicose veins: a case report
Authors: Caggiati A , Franceschini M
Published: February 2012

Cartilaginous metaplasia of superficial veins was found in a 64-year-old woman who underwent surgery for varicose veins. At operation, some varicose veins of the medial thigh were semi-rigid and fibroelastic to the touch. Histology revealed that half the lumen was occupied by chondroid tissue. The other half was obliterated by fibrous tissue, typical of post-thrombotic involution. Possible causes of cartilaginous metaplasia are briefly discussed.
Embedding Risk Attitudes in a Scheduling Model: Application to the Study of Commuting Departure Time
Authors: Li Zheng , Tirachini Alejandro , Hensher David A.
Published: February 2012

In traditional travel time reliability valuation studies, the value of travel time savings and the value of travel time reliability (or reduced time variability) are estimated within a linear utility functional form, which assumes risk-neutral attitudes for decision makers. In this paper, we develop nonlinear scheduling models to address both risk attitude and preference in the context of a stated choice experiment of car commuters facing risky choices where the risk is associated with the trip time. We also investigate unobserved between-individual heterogeneity in time-related parameters and risk attitudes using a mixed multinomial logit model. The willingness-to-pay values for reducing the mean travel time and variability (earlier/later than the preferred arrival time) are also estimated within the nonlinear scheduling framework. The model is then used to estimate preferred departure times for commuters, assuming that random link capacities are the source of travel time variability. Results show that the more variable travel times are, the earlier commuters depart and that the nonlinear scheduling model predicts earlier optimal departure times than the linear scheduling model does. The application in this paper helps to bridge the gap between theory and practice.
Profit Maximizing Distributed Service System Design with Congestion and Elastic Demand
Authors: Aboolian Robert , Berman Oded , Krass Dmitry
Published: February 2012

In this paper we develop a service network design model that explicitly takes into account the elasticity of customer demand with respect to travel distance and congestion delays. The model incorporates a feedback loop between customer demand and congestion at the facilities. The problem is to determine the number of facilities, their locations, their service capacity, and the assignment of customers to facilities so as to maximize the overall profit of the system. Two versions of the problem are presented. In one, each facility is modeled as an M/M/1 queuing system where the service rate is a decision variable; in the other one, the facility is modeled as an M/M/k queuing model where the service rate is given, but the number k is a decision variable. An exact algorithm and heuristics are developed and tested via computational experiments. Although our model is of the “directed choice” type where the assignment of customers to facilities is controlled by the decision maker, computational results show that in the vast majority of cases the customers are assigned to the utility-maximizing facility, indicating that there is no conflict between the customers' and decision makers' goals. A case study of locating preventive medicine clinics in Toronto, Ontario, illustrates the model.
Feasibility of the Pickup and Delivery Problem with Fixed Partial Routes: A Complexity Analysis
Authors: Berbeglia Gerardo , Pesant Gilles , Rousseau Louis-Martin
Published: February 2012

In the pickup and delivery problem (PDP) a fleet of vehicles must serve customers' requests, which consist of transporting objects from their origins to their destinations. We introduce the PDP with fixed partial routes (PDP-FPR), in which some partial routes are given, and the problem consists in obtaining a solution (a set of routes) that includes those partial routes. We have analyzed the complexity of determining whether or not a feasible solution exists for this problem as well as for some relaxations of it. Checking the feasibility of the PDP-FPR and some of its relaxations is shown to be NP-complete, whereas for other relaxations, the problem was proved to be polynomial-time solvable.
An Adaptive Variable Neighborhood Search Algorithm for a Vehicle Routing Problem Arising in Small Package Shipping
Authors: Stenger Andreas , Vigo Daniele , Enz Steffen , Schwind Michael
Published: February 2012

In this paper, we investigate a routing problem arising in the last-mile delivery of small packages. The problem, called Multi-Depot Vehicle Routing Problem with Private fleet and Common carriers (MDVRPPC), is an extension of the Multi-Depot Vehicle Routing Problem (MDVRP) where customers can either be served by the private fleet based at self-owned depots or by common carriers, i.e., subcontractors. We develop an effective Variable Neighborhood Search algorithm based on the use of cyclic-exchange neighborhoods that incorporates an adaptive mechanism to bias the random shaking step. The approach is successfully used to solve MDVRPPC as well as closely related problems, such as the MDVRP and the single-depot VRP with Private fleet and Common carriers (VRPPC), obtaining high quality solutions within short computing time. Our extensive testing on these problems shows the positive impact of the adaptive mechanism with respect to a standard VNS algorithm.
Mixing and matching causing taper wear
Authors: Chana R. , Esposito C. , Campbell P. A. , Walter W. K. , Walter W. L.
Published: February 2012

We report a case of a male patient presenting with bilateral painful but apparently well-positioned and -fixed large-diameter metal-on-metal hip replacements four years post-operatively. Multiple imaging modes revealed a thick-walled, cystic expansile mass in communication with the hip joint (a pseudotumour). Implant retrieval analysis and tissue culture eliminated high bearing wear or infection as causes for the soft-tissue reaction, but noted marked corrosion of the modular neck taper adaptor and corrosion products in the tissues. Therefore, we believe corrosion products from the taper caused by mismatch of the implant components led to pseudotumour formation requiring revision.
Early results of a novel technique using multiple small tantalum pegs for the treatment of osteonecrosis of the femoral head
Authors: Malizos K. N. , Papasoulis E. , Dailiana Z. H. , Papatheodorou L. K. , Varitimidis S. E.
Published: February 2012

The introduction of a trabecular tantalum rod has been proposed for the management of early-stage osteonecrosis of the femoral head but serves as a single-point of support of the necrotic lesion. We describe a technique using two or three 4.2 mm (or later 4.7 mm) tantalum pegs for the prevention of collapse of the necrotic lesion. We prospectively studied 21 patients (26 hips) with non-traumatic osteonecrosis of the femoral head treated in this manner. Of these, 21 patients (24 hips) were available for radiological and clinical evaluation at a mean follow-up of 46 months (18 to 67). Radiological assessment showed that only eight hips deteriorated according to the Association Research Circulation Osseous classification, and four hips according to the Classification of the Japanese Investigation Committee of Health and Welfare. Functional improvement was obtained with an improvement in the mean Harris hip score from 65.2 (33.67 to 95) to 88.1 (51.72 to 100), the mean Merle D’Aubigné-Postel score from 13 (6 to 18) to 16 (11 to 18), a mean visual analogue score for pain from 5.2 (0 to 9.5) to 2.6 (0 to 7), and the mean Short-Form 36 score from 80.4 (56.8 to 107.1) to 92.4 (67.5 to 115.7). Of these 24 hips followed for a minimum of 18 months, three were considered as failures at the final follow-up, having required total hip replacement. One of the hips without full follow-up was also considered to be a failure. In more than two-thirds of the surviving hips a satisfactory clinical outcome was achieved with promising radiological findings. The estimated mean implant survival was 60 months (95% confidence interval 53.7 to 66.3).
The 15° face-changing acetabular component for treatment of osteoarthritis secondary to developmental dysplasia of the hip
Authors: Zahos K. , Mehendale S. , Ward A. J. , Smith E. J. , Nichols M.
Published: February 2012

We report the use of a 15° face-changing cementless acetabular component in patients undergoing total hip replacement for osteoarthritis secondary to developmental dysplasia of the hip. The rationale behind its design and the surgical technique used for its implantation are described. It is distinctly different from a standard cementless hemispherical component as it is designed to position the bearing surface at the optimal angle of inclination, that is, < 45°, while maximising the cover of the component by host bone.