bluuebunny/crossref_metadata_2025 huggingface dataset:
Mast Cells and Histamine: Do They Influence Placental Vascular Network and Development in Preeclampsia?
Authors: Szewczyk Grzegorz , Pyzlak Michał , Klimkiewicz Jakub , Śmiertka Wacław , Miedzińska-Maciejewska Magdalena , Szukiewicz Dariusz
Published: June 2012

The physiological course of pregnancy is closely related to adequate development of the placenta. Shallow invasion of trophoblast as well as decreased development of the placental vascular network are both common features of preeclampsia. To better understand the proangiogenic features of mast cells, in this study we aim to identify the potential relationship between the distribution of mast cells within the placenta and vascular network development.Material and Methods. Placentas from preeclampsia-complicated pregnancies () and from physiological pregnancies () were acquired after cesarean section. The concentration of histamine was measured, and immunohistochemical staining for mast cell tryptase was performed. Morphometric analysis was then performed.Results. We noticed significant differences between the examined groups. Notably, in the preeclampsia group compared to the control group, we observed a higher mean histamine concentration, higher mast cell density (MCD), lower mean mast cell (MMCA) and lower vascular/extravascular (V/EVT) index. In physiological pregnancies, a positive correlation was observed between the histamine concentration and V/VEVT index as well as MCD and the V/VEVT index. In contrast, a negative correlation was observed between MMCA and the V/EVT index in physiological pregnancies.Conclusions. Based on the data from our study, we suggest that a differential distribution of mast cells and corresponding changes in the concentration of histamine are involved in the defective placental vascularization seen in preeclamptic placentas.
Entropy-Based Clutter Rejection for Intrawall Diagnostics
Authors: Solimene Raffaele , D'Alterio Antonietta
Published: June 2012

The intrawall diagnostic problem of detecting localized inhomogeneities possibly present within the wall is addressed. As well known, clutter arising from masonry structure can impair detection of embedded scatterers due to high amplitude reflections that wall front face introduces. Moreover, internal multiple reflections also can make it difficult ground penetrating radar images (radargramms) interpretation. To counteract these drawbacks, a clutter rejection method, properly tailored on the wall features, is mandatory. To this end, here we employ a windowing strategy based on entropy measures of temporal traces “similarity.” Accordingly, instants of time for which radargramms exhibit entropy values greater than a prescribed threshold are “silenced.” Numerical results are presented in order to show the effectiveness of the entropy-based clutter rejection algorithm. Moreover, a comparison with the standard average trace subtraction is also included.
Topical Application of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) Accelerates Wound Healing in Diabetic Rabbits
Authors: Al-Elq Abdulmohsen H. , Sadat-Ali Mir , Elsharawy Mohamed , Al-Habdan Ibrahim , Al-Aqeel Fatin Othman , Naim Magda M.
Published: June 2012

Objective. Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits.Materials and Methods. Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed.Results. There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group.Conclusion. Topical application of SHMSP improves wound healing in diabetic rabbits.
Transcatheter Closure of Atrial Septal Defects in Children, Middle-Aged Adults, and Older Adults: Failure Rates, Early Complications; and Balloon Sizing Effects
Authors: Vijarnsorn Chodchanok , Durongpisitkul Kritvikrom , Chanthong Prakul , Chungsomprasong Paweena , Soongswang Jarupim , Loahaprasitiporn Duangmanee , Nana Apichart
Published: June 2012

Objectives. To compare the failure ratio and inhospital complications across three age groups of patients and to investigate the effects of balloon sizing on the success and the device diameter.Methods. This retrospective review was of 665 patients who had been listed for transcatheter-based closure of ASD between 1999 and 2010. The patients were divided into three age groups: children (<18 years;n=183), adults (18–50 years;n=337), and older adults (>50 years;n=145). Procedural outcomes and early complications were reviewed. Use of balloon sizing was explored for its benefits.Results. Overall, failure of closure was 6.6% (n=44). Use of balloon sizing tended to lead to a smaller device/defect ratio that was comparable to procedures without balloon sizing, though it did not predict the success rate (OR 1.4, 95% CI 0.7–2.3). Seven patients reported device embolization (1%). No mortalities were noted. In-hospital complications were 3.4%, with common complications, being vascular complications (1.4%) and cardiac arrhythmia (1.1%). No differences in failure rate or events were found among the three groups.Conclusion. Transcather closure of ASD is feasible and safe, regardless of the patient’s age. A low rate of early complications was noted. Balloon sizing does not aggravate an oversizing of the device, but does not predict success.
Role of MHC-Linked Susceptibility Genes in the Pathogenesis of Human and Murine Lupus
Authors: Relle Manfred , Schwarting Andreas
Published: June 2012

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies against nuclear antigens and a systemic inflammation that can damage a broad spectrum of organs. SLE patients suffer from a wide variety of symptoms, which can affect virtually almost any tissue. As lupus is difficult to diagnose, the worldwide prevalence of SLE can only be roughly estimated to range from 10 and 200 cases per 100,000 individuals with dramatic differences depending on gender, ethnicity, and location. Although the treatment of this disease has been significantly ameliorated by new therapies, improved conventional drug therapy options, and a trained expert eye, the underlying pathogenesis of lupus still remain widely unknown. The complex etiology reflects the complex genetic background of the disease, which is also not well understood yet. However, in the past few years advances in lupus genetics have been made, notably with the publication of genome-wide association studies (GWAS) in humans and the identification of susceptibility genes and loci in mice. This paper reviews the role of MHC-linked susceptibility genes in the pathogenesis of systemic lupus erythematosus.
Placental Teratoma Presenting as a Lobulated Mass behind the Neck of Fetus: A Case Report
Authors: Prashanth Adiga , Lavanya Rai , Girisha K. M. , Mundkur Anjali
Published: June 2012

Placental teratoma is a rare nontrophoblastic benign tumour, which is thought to arise from germ cells. These tumours contain elements derived from multiple germ cell layers. We report a case of teratoma, where on ultrasound; there were two echogenic masses of 4 cm × 5 cm and 3 cm × 4 cm, arising from the placenta. Elective lower segment cesarean section was done in view of breech presentation at 38 weeks of gestation. Gross examination of the placenta showed two lobulated masses of 5 cm × 5 cm and 4 cm × 4.5 cm, respectively. Histopathological examination of the placenta was suggestive of teratoma of the placenta. The fetus was normal.The maternal and fetal outcome was good.
Current Mechanism in -Gated Metal-Oxide-Semiconductor Devices
Authors: Pakma Osman
Published: June 2012

The present study aimed to examine the current density-voltage (J-V) characteristics of Al/HfO2/p-Si (MOS) structure at temperatures ranging between 100 and 320 K and to determine the structure’s current transport mechanism. The HfO2film was coated on a single side of the p-Si (111) crystal using the spin coating method. TheJ-Vmeasurements of the obtained structure at the temperatures between 100 and 320 K revealed that the current transport mechanism in the structure was compatible with the Schottky emission theory. The Schottky emission theory was also used to calculate the structure’s Schottky barrier heights (), dielectric constants () and refractive index values of the thin films at each temperature value. The dielectric constant and refractive index values were observed to decrease at decreasing temperatures. The capacitance-voltage (C-V) and conductance-voltage (G/ω-V) characteristics of Al/HfO2/p-Si (MOS) structure was measured in the temperature range of 100–320 K. The values of measuredCandG/ωdecrease in accumulation and depletion regions with decreasing temperature due to localized at Si/HfO2interface.
Incidence of Pregnancy after Initiation of Antiretroviral Therapy in South Africa: A Retrospective Clinical Cohort Analysis
Authors: Westreich Daniel , Maskew Mhairi , Rubel Dennis , MacDonald Pippa , Jaffray Imogen , Majuba Pappie
Published: June 2012

Background. Little is known about rates of incident pregnancy among HIV-positive women initiating highly active antiretroviral therapy (HAART).Methods. We conducted a retrospective clinical cohort study among therapy-naïve women ages 18–45 initiating HAART between 1 April 2004 and 30 September 2009 at an adult HAART clinic in Johannesburg, South Africa. We used Poisson regression to characterize rates and rate ratios of pregnancy.Results. We evaluated 5,996 women who experienced 727 pregnancies during 14,095 person-years at risk. The overall rate of pregnancy was 5.2 per 100 person-years (95% confidence limits [CL] 4.8, 5.5). By six years, cumulative incidence of first pregnancy was 22.9% (95% CL 20.6%, 25.4%); among women ages 18–25 at HAART initiation, cumulative incidence was 52.2% (95% CL 35.0%, 71.8%). The strongest predictor of incidence of pregnancy was age, with women 18–25 having 13.2 times the rate of pregnancy of women ages 40–45 in adjusted analysis. CD4 counts below 100 and worse adherence to HAART were associated with lower rates of incident pregnancy.Conclusions. Women experience high rates of incident pregnancy after HAART initiation. Understanding which women are most likely to experience pregnancy will help planning and future efforts to understand the implications of pregnancy for response to HAART.
Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma
Authors: Chao Chun , Silverberg Michael J. , Martínez-Maza Otoniel , Chi Margaret , Abrams Donald I. , Haque Reina , Zha Hongbin D. , McGuire Michelle , Xu Lanfang , Said Jonathan
Published: June 2012

Purpose: Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.

Experimental Design: HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.

Results: Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6–6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].

Conclusion: Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs. Clin Cancer Res; 18(17); 4702–12. ©2012 AACR.
A 50-Gene Intrinsic Subtype Classifier for Prognosis and Prediction of Benefit from Adjuvant Tamoxifen
Authors: Chia Stephen K. , Bramwell Vivien H. , Tu Dongsheng , Shepherd Lois E. , Jiang Shan , Vickery Tammi , Mardis Elaine , Leung Samuel , Ung Karen , Pritchard Kathleen I. , Parker Joel S. , Bernard Philip S. , Perou Charles M. , Ellis Matthew J. , Nielsen Torsten O.
Published: June 2012

Purpose: Gene expression profiling classifies breast cancer into intrinsic subtypes based on the biology of the underlying disease pathways. We have used material from a prospective randomized trial of tamoxifen versus placebo in premenopausal women with primary breast cancer (NCIC CTG MA.12) to evaluate the prognostic and predictive significance of intrinsic subtypes identified by both the PAM50 gene set and by immunohistochemistry.

Experimental Design: Total RNA from 398 of 672 (59%) patients was available for intrinsic subtyping with a quantitative reverse transcriptase PCR (qRT-PCR) 50-gene predictor (PAM50) for luminal A, luminal B, HER-2–enriched, and basal-like subtypes. A tissue microarray was also constructed from 492 of 672 (73%) of the study population to assess a panel of six immunohistochemical IHC antibodies to define the same intrinsic subtypes.

Results: Classification into intrinsic subtypes by the PAM50 assay was prognostic for both disease-free survival (DFS; P = 0.0003) and overall survival (OS; P = 0.0002), whereas classification by the IHC panel was not. Luminal subtype by PAM50 was predictive of tamoxifen benefit [DFS: HR, 0.52; 95% confidence interval (CI), 0.32–0.86 vs. HR, 0.80; 95% CI, 0.50–1.29 for nonluminal subtypes], although the interaction test was not significant (P = 0.24), whereas neither subtyping by central immunohistochemistry nor by local estrogen receptor (ER) or progesterone receptor (PR) status were predictive. Risk of relapse (ROR) modeling with the PAM50 assay produced a continuous risk score in both node-negative and node-positive disease.

Conclusions: In the MA.12 study, intrinsic subtype classification by qRT-PCR with the PAM50 assay was superior to IHC profiling for both prognosis and prediction of benefit from adjuvant tamoxifen. Clin Cancer Res; 18(16); 4465–72. ©2012 AACR.
Measuring Agreement, More Complicated Than It Seems
Authors: van Stralen K.J. , Dekker F.W. , Zoccali C. , Jager K.J.
Published: June 2012

In medicine, before replacing an old device by a new one, we need to know whether the results of the old and new device are similar. This is called determining the agreement between methods. In this paper, we will first discuss various ways to determine the agreement between methods to measure continuous variables, including the t test, the correlation coefficient and the Bland-Altman plot. In the second part, we will discuss methods to determine the agreement between categorical variables, like the χ2 test and Cohen’s ĸ. The latter are often used when studying the agreement between clinicians, definitions, formulas or different data sources.
Particulate Systems for Targeting of Macrophages: Basic and Therapeutic Concepts
Authors: Moghimi S.M. , Parhamifar L. , Ahmadvand D. , Wibroe P.P. , Andresen T.L. , Farhangrazi Z.S. , Hunter A.C.
Published: June 2012

Particulate systems in the form of liposomes, polymeric micelles, polymeric nano- and microparticles, and many others offer a rational approach for selective delivery of therapeutic agents to the macrophage from different physiological portals of entry. Particulate targeting of macrophages and intracellular drug release processes can be optimized through modifications of the drug carrier physicochemical properties, which include hydrodynamic size, shape, composition and surface characteristics. Through such modifications together with understanding of macrophage cell biology, targeting may be aimed at a particular subset of macrophages. Advances in basic and therapeutic concepts of particulate targeting of macrophages and related nanotechnology approaches for immune cell modifications are discussed.
Treatment of Resistant Glomerular Diseases with Adrenocorticotropic Hormone Gel: A Prospective Trial
Authors: Bomback Andrew S. , Canetta Pietro A. , Beck Jr. Laurence H. , Ayalon Rivka , Radhakrishnan Jai , Appel Gerald B.
Published: June 2012

Background: Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies. Methods: In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to <0.5 g/g (complete remission) or 0.5–3.5 g/g (partial remission). Results: The study included 5 subjects with resistant idiopathic MN, 5 subjects with resistant MCD (n = 2)/FSGS (n = 3), and 5 subjects with resistant IgA nephropathy. Two resistant MN subjects achieved partial remission on ACTH therapy, although 3 achieved immunologic remission of disease (PLA2R antibody disappeared by 4 months of therapy). One subject with resistant FSGS achieved complete remission on ACTH; one subject with resistant MCD achieved partial remission but relapsed within 4 weeks of stopping ACTH. Two subjects with resistant IgA nephropathy demonstrated >50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response. Conclusions: ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease.
Effect of Al on microstructure and impact property of surfacing repair layer of rail
Authors: Li D , Gou G Q , Liu Y , Zhu T H , Ji H , Chen H
Published: June 2012

Failed rail can be repaired using self-shielded flux cored wire. Aluminium powder is always added to the flux cored wire to protect the weld pool. However, the Al content affects the microstructure and property of the surfacing layer significantly. Therefore, the microstructure and impact property of the surfacing layer of the rail with different Al contents were analysed. Meanwhile, the formation mechanism of the inclusions was calculated by thermodynamic method. The results show that the pore sensitivity of the surfacing layer is high when the Al content is <0·79 wt-%. The impact energy decreases with the increase in Al content. The thermodynamic calculated results show that the inclusion in the surfacing layer is AlN when the Al content is >1·89 wt-%. In contrast, they are mainly Al2O3 when the Al content is <1·45 wt-%. The thermodynamic calculated results are well agreed with the experimental ones.
Si–Mo–Cr coating for C/SiC coated carbon/carbon composites against oxidation
Authors: Zhang Y.-L. , Li H.-J. , Wang P.-Y. , Li K.-Z. , Zeng X.-R.
Published: June 2012

Si–Mo–Cr oxidation protective coating has been prepared on the surface of C/SiC coated carbon/carbon (C/C) composites by pack cementation technique. The phase composition and microstructure of the as prepared coatings were characterised by X-ray diffraction, scanning electron microscopy (SEM) and energy dispersion spectrum (EDS) analyses. The oxidation behaviour of the coated C/C specimens was also investigated at 1500°C in air. The results show that the as prepared coating is mainly composed of SiC, MoSi2, CrSi2 and Si. The coating characterised by excellent oxidation resistance and thermal shock resistance can effectively protect C/C composites from oxidation for 186 h at 1500°C in air and endure the thermal cycle between 1500°C and room temperature for nine times, while the corresponding weight loss is only 0·33%. The excellent oxidation protection ability of the coating is primarily attributed to the formation of a compound glass layer, including SiO2 and Cr2O3.
Necdin modulates proliferative cell survival of human cells in response to radiation-induced genotoxic stress
Authors: Lafontaine Julie , Tchakarska Guergana , Rodier Francis , Mes-Masson Anne-Marie
Published: June 2012

Background

The finite replicative lifespan of cells, termed cellular senescence, has been proposed as a protective mechanism against the proliferation of oncogenically damaged cells, that fuel cancer. This concept is further supported by the induction of premature senescence, a process which is activated when an oncogene is expressed in normal primary cells as well as following intense genotoxic stresses. Thus, deregulation of genes that control this process, like the tumor suppressor p53, may contribute to promoting cancer by allowing cells to bypass senescence. A better understanding of the genes that contribute to the establishment of senescence is therefore warranted. Necdin interacts with p53 and is also a p53 target gene, although the importance of Necdin in the p53 response is not clearly understood.

Methods

In this study, we first investigated Necdin protein expression during replicative senescence and premature senescence induced by gamma irradiation and by the overexpression of oncogenic RasV12. Gain and loss of function experiments were used to evaluate the contribution of Necdin during the senescence process.

Results

Necdin expression declined during replicative aging of IMR90 primary human fibroblasts or following induction of premature senescence. Decrease in Necdin expression seemed to be a consequence of the establishment of senescence since the depletion of Necdin in human cells did not induce a senescence-like growth arrest nor a flat morphology or SA-β-galactosidase activity normally associated with senescence. Similarly, overexpression of Necdin did not affect the life span of IMR90 cells. However, we demonstrate that in normal human cells, Necdin expression mimicked the effect of p53 inactivation by increasing radioresistance.

Conclusion

This result suggests that Necdin potentially attenuate p53 signaling in response to genotoxic stress in human cells and supports similar results describing an inhibitory function of Necdin over p53-dependent growth arrest in mice.
Analysis of questioning technique during classes in medical education
Authors: Cho Young Hye , Lee Sang Yeoup , Jeong Dong Wook , Im Sun Ju , Choi Eun Jung , Lee Sun Hee , Baek Sun Yong , Kim Yun Jin , Lee Jeong Gyu , Yi Yu Hyone , Bae Mi Jin , Yune So Jung
Published: June 2012

Background

Questioning is one of the essential techniques used by lecturers to make lectures more interactive and effective. This study surveyed the perception of questioning techniques by medical school faculty members and analyzed how the questioning technique is used in actual classes.

Methods

Data on the perceptions of the questioning skills used during lectures was collected using a self‒questionnaire for faculty members (N = 33) during the second semester of 2008. The questionnaire consisted of 18 items covering the awareness and characteristics of questioning skills. Recorded video tapes were used to observe the faculty members’ questioning skills.

Results

Most faculty members regarded the questioning technique during classes as being important and expected positive outcomes in terms of the students’ participation in class, concentration in class and understanding of the class contents. In the 99 classes analyzed, the median number of questions per class was 1 (0–29). Among them, 40 classes (40.4 %) did not use questioning techniques. The frequency of questioning per lecture was similar regardless of the faculty members’ perception. On the other hand, the faculty members perceived that their usual wait time after question was approximately 10 seconds compared to only 2.5 seconds measured from video analysis. More lecture‒experienced faculty members tended to ask more questions in class.

Conclusions

There were some discrepancies regarding the questioning technique between the faculty members’ perceptions and reality, even though they had positive opinions of the technique. The questioning skills during a lecture need to be emphasized to faculty members.
Forelimb EMG-based trigger to control an electronic spinal bridge to enable hindlimb stepping after a complete spinal cord lesion in rats
Authors: Gad Parag , Woodbridge Jonathan , Lavrov Igor , Zhong Hui , Roy Roland R , Sarrafzadeh Majid , Edgerton V Reggie
Published: June 2012

Background

A complete spinal cord transection results in loss of all supraspinal motor control below the level of the injury. The neural circuitry in the lumbosacral spinal cord, however, can generate locomotor patterns in the hindlimbs of rats and cats with the aid of motor training, epidural stimulation and/or administration of monoaminergic agonists. We hypothesized that there are patterns of EMG signals from the forelimbs during quadrupedal locomotion that uniquely represent a signal for the “intent” to step with the hindlimbs. These observations led us to determine whether this type of “indirect” volitional control of stepping can be achieved after a complete spinal cord injury. The objective of this study was to develop an electronic bridge across the lesion of the spinal cord to facilitate hindlimb stepping after a complete mid-thoracic spinal cord injury in adult rats.

Methods

We developed an electronic spinal bridge that can detect specific patterns of EMG activity from the forelimb muscles to initiate electrical-enabling motor control ( eEmc) of the lumbosacral spinal cord to enable quadrupedal stepping after a complete spinal cord transection in rats. A moving window detection algorithm was implemented in a small microprocessor to detect biceps brachii EMG activity bilaterally that then was used to initiate and terminate epidural stimulation in the lumbosacral spinal cord. We found dominant frequencies of 180–220 Hz in the EMG of the forelimb muscles during active periods, whereas these frequencies were between 0–10 Hz when the muscles were inactive.

Results and conclusions

Once the algorithm was validated to represent kinematically appropriate quadrupedal stepping, we observed that the algorithm could reliably detect, initiate, and facilitate stepping under different pharmacological conditions and at various treadmill speeds.
17beta-hydroxysteroid dehydrogenase type 1 modulates breast cancer protein profile and impacts cell migration
Authors: Aka Juliette A , Zerradi Mouna , Houle François , Huot Jacques , Lin Sheng-Xiang
Published: June 2012

Introduction

Human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a steroid-converting enzyme that has long been known to play critical roles in estradiol synthesis and more recently in dihydrotestosterone (DHT) inactivation, showing a dual function that promotes breast cancer cell proliferation. Previously, we reported the first observation of the influence of the enzyme on endogenous estrogen-responsive gene expression. Here, we demonstrate the impact of 17β-HSD1 expression on the breast cancer cell proteome and investigate its role in cell migration.

Methods

17β-HSD1 was stably transfected in MCF7 cells and the proteome of the generated cells overexpressing 17β-HSD1 (MCF7-17βHSD1 cells) was compared to that of the wild type MCF7 cells. Proteomics study was performed using two-dimensional gel electrophoresis followed by mass spectrometry analysis of differentially expressed protein spots. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to investigate the transcription of individual gene. The effect of 17β-HSD1 on MCF7 cell migration was verified by a wound-healing assay.

Results

Proteomic data demonstrate that the expression of more than 59 proteins is modulated following 17β-HSD1 overexpression. 17β-HSD1 regulates the expression of important genes and proteins that are relevant to cell growth control, such as BRCA2 and CDKN1A interacting protein (BCCIP) and proliferating cell nuclear antigen (PCNA) which are down- and upregulated in MCF7-17βHSD1 cells, respectively. RT-qPCR data reveal that 17β-HSD1 increases the mRNA levels of estrogen receptors (ER) alpha and beta by 171 and 120%, respectively, while decreasing that of the androgen receptor by 64%. Interestingly, 17β-HSD1 increases the mRNA transcript (by 3.6 times) and the protein expression of the metastasis suppressor gene nm23-H1 and the expression of the two enzymes are closely correlated. We have further shown that 17β-HSD1 expression is associated with an increase of MCF7 cell migration.

Conclusions

In addition to the regulation of important genes, we have demonstrated for the first time that 17β-HSD1 increases breast cancer cell migration, in spite of its positive regulation of the antimetastatic gene NM23. This is also correlated to its stimulation of breast cancer cell growth, further confirming its targeting in ER positive breast cancer. The novel findings in this study suggest several directions for future research on the contribution of 17β-HSD1 to breast cancer progression and related treatment.
Detecting a salt dome overhang with magnetotellurics: 3D inversion methodology and synthetic model studies
Authors: Avdeeva Anna , Avdeev Dmitry , Jegen Marion
Published: June 2012

Detecting a salt dome overhang is known to be problematic by seismic methods alone. We used magnetotellurics (MT) as a complementary method to seismics to investigate the detectability of a salt dome overhang. A comparison of MT responses for 3D synthetic salt models with and without overhang shows that MT is very sensitive to shallow salt structures and suggests that it should be possible to detect an overhang. To further investigate the resolution capability of MT for a salt dome overhang, we performed a 3D MT inversion study and investigated the impact of model parametrization and regularization. We showed that using the logarithms of the conductivities as model parameters is crucial for inverting data from resistive salt structures because, in this case, commonly used Tikhonov-type stabilizers work more equally for smoothing the resistive and conductive structures. The use of a logarithmic parametrization also accelerated the convergence and produced better inversion results. When the Laplace operator was used as a regularization functional, we still observed that the inversion algorithm allows spatial resistivity gradients. These spatial gradients are reduced if a regularization based on first derivatives in contrast to the Laplace operator is introduced. To demonstrate the favorable performance when logarithmic parametrization and gradient-based regularization are employed, we first inverted a data set simulated for a simple model of two adjacent blocks. Subsequently, we applied the code to a more realistic salt dome overhang detectability study. The results from the detectability study are encouraging and suggest that 3D MT inversion can be applied to decide whether the overhang is present in the shallow salt structure even in the case when only profile data are available. However, to resolve the overhang, a dense MT site coverage above the flanks of the salt dome is required.
BRCA Mutation Frequency and Patterns of Treatment Response in BRCA Mutation–Positive Women With Ovarian Cancer: A Report From the Australian Ovarian Cancer Study Group
Authors: Alsop Kathryn , Fereday Sian , Meldrum Cliff , deFazio Anna , Emmanuel Catherine , George Joshy , Dobrovic Alexander , Birrer Michael J. , Webb Penelope M. , Stewart Colin , Friedlander Michael , Fox Stephen , Bowtell David , Mitchell Gillian
Published: June 2012

Purpose

The frequency of BRCA1 and BRCA2 germ-line mutations in women with ovarian cancer is unclear; reports vary from 3% to 27%. The impact of germ-line mutation on response requires further investigation to understand its impact on treatment planning and clinical trial design.

Patients and Methods

Women with nonmucinous ovarian carcinoma (n = 1,001) enrolled onto a population-based, case-control study were screened for point mutations and large deletions in both genes. Survival outcomes and responses to multiple lines of chemotherapy were assessed.

Results

Germ-line mutations were found in 14.1% of patients overall, including 16.6% of serous cancer patients (high-grade serous, 22.6%); 44% had no reported family history of breast or ovarian cancer. Patients carrying germ-line mutations had improved rates of progression-free and overall survival. In the relapse setting, patients carrying mutations more frequently responded to both platin- and nonplatin-based regimens than mutation-negative patients, even in patients with early relapse after primary treatment. Mutation-negative patients who responded to multiple cycles of platin-based treatment were more likely to carry somatic BRCA1/2 mutations.

Conclusion

BRCA mutation status has a major influence on survival in ovarian cancer patients and should be an additional stratification factor in clinical trials. Treatment outcomes in BRCA1/2 carriers challenge conventional definitions of platin resistance, and mutation status may be able to contribute to decision making and systemic therapy selection in the relapse setting. Our data, together with the advent of poly(ADP-ribose) polymerase inhibitor trials, supports the recommendation that germ-line BRCA1/2 testing should be offered to all women diagnosed with nonmucinous, ovarian carcinoma, regardless of family history.
Solution of the Pellet Equation by use of the Orthogonal Collocation and Least Squares Methods: Effects of Different Orthogonal Jacobi Polynomials
Authors: Solsvik Jannike , Jakobsen Hugo
Published: June 2012

Two numerical methods in the family of weighted residual methods; the orthogonal collocation and least squares methods, are used within the spectral framework to solve a linear reaction-diffusion pellet problem with slab and spherical geometries. The node points are in this work taken as the roots of orthogonal polynomials in the Jacobi family. Two Jacobi polynomial parameters, alpha and beta, can be used to tune the distribution of the roots within the domain. Further, the internal points and the boundary points of the boundary-value problem can be given according to: i) Gauss-Lobatto-Jacobi points, or ii) Gauss-Jacobi points plus the boundary points. The objective of this paper is thus to investigate the influence of the distribution of the node points within the domain adopting the orthogonal collocation and least squares methods. Moreover, the results of the two numerical methods are compared to examine whether the methods show the same sensitivity and accuracy to the node point distribution. The notifying findings are as follows: i) The Legendre polynomial, i.e., alpha=beta=0, is a very robust Jacobi polynomial giving the better condition number of the coefficient matrix and the polynomial also give good behavior of the error as a function of polynomial order. This polynomial gives good results for small and large gradients within both slab and spherical pellet geometries. This trend is observed for both of the weighted residual methods applied. ii) Applying the least squares method the error decreases faster with increasing polynomial order than observed with the orthogonal collocation method. However, the orthogonal collocation method is not so sensitive to the choice of Jacobi polynomial and the method also obtains lower error values than the least squares method due to favorable lower condition numbers of the coefficient matrices. Thus, for this particular problem, the orthogonal collocation method is recommended above the least squares method. iii) The orthogonal collocation method show minor differences between Gauss-Lobatto-Jacobi points and Gauss-Jacobi plus boundary points.
Use of X-ray Tomography for the Experimental Verification of a Mathematical Model for the Recovery of Cu and Cd in a Flow-By Porous Electrode Reactor.
Authors: Olvera Oscar G. , Lapidus-Lavine Gretchen T.
Published: June 2012

In this work a mathematical model for a flow-by electrochemical reactor operating galvanostatically for the Cu and Cd electrodeposition and hydrogen evolution reaction (HER) has been proposed. X-ray computed tomography was used to measure experimental metallic distributions. Good agreement was found between the experimental measurements and model predictions for conversion, current efficiencies, electrode potential and metallic deposit distributions. Differences were observed between experimental results and model predictions and were attributed to a change in Cd electrodeposition and HER kinetics.
Grain Sorption Equilibria of Algarroba Flour
Authors: Leon Paula G. , Tolaba Marcela P. , Reid Carolina , Mocciola Julia R. , Pollio MarÃ­a L.
Published: June 2012

Water vapour sorption of white and black algarroba flour obtained from Prosopis alba and Prosopis nigra was determined at 20, 30 and 40Â°C in the range of 0.089-0.851 water activity by mean of isopiestic method. The isotherms were adequately modelled using GAB equation. Equations based on the enthalpy-entropy compensation theory, was used to describe the temperature effect on water sorption isotherms and to obtain predicted values of the isosteric heat of sorption and its moisture content dependence. The predicted values agree with the experimental isosteric heat values calculated by means of Clausius-Clayperon equation.
Solvency Determinants of Conventional Life Insurers and Takaful Operators
Authors: Yakob Rubayah , Yusop Zulkornain , Radam Alias , Ismail Noriszura
Published: June 2012

The business of insurance is based on the trust of its policyholders, who expect that their losses will be compensated should the need arise at any time. Thus, sound financial conditions constitute the most important criterion for insurance firms, as well as for takaful operators. Although the policyholder may be the most important source of insurer finance, or a debt holder from an economic point of view through premium payments, the policyholder is not well informed in assessing the financial strength or solvency of the life insurer. Various measures of the solvency of the insurer are used in the industry, such as margin of solvency (MOS), risk based capital (RBC), and claim paying ability (CPA) rating. Unfortunately, none of these can provide information to policyholders on the financial position of the insurer. This is because the MOS and RBC for each insurer is the company's and regulator’s confidential information. However, for the CPA rating, it is limited to insurers who wish to be evaluated, and therefore the assessment is not comprehensive. Because of these shortcomings, this study provides a platform for policyholders to get an idea of the solvency of the insurers/takaful operators. Furthermore, this study identifies factors that affect the solvency of the insurers/takaful operators in Malaysia. Using random effects regression on panel data for 2003-2007, it is determined that investment income, total benefit paid to capital and surplus ratio, financial leverage, and liquidity are significantly related to solvency, in which the investment income has a positive relationship, while the other three have a negative relationship. From the results obtained, the policyholders/consumers can assess the insurers’ financial strength through the solvency determinants of the insurers/takaful operators, even though the actual level of solvency is not known. To some extent, this information can help policyholders/consumers make smarter choices in choosing the insurers/takaful operators
Making Policy Without Parameters: Obtaining Data on the Nonprofit Sector in a Local Community
Authors: Roudebush Margaret M. , Brudney Jeffrey L.
Published: June 2012

This study began with an effort to obtain data on the economic contribution of the nonprofit sector in a large, metropolitan community to inform policy-makers. Despite the growing interest of policy-makers in the nonprofit sector, and the importance of accurate, reliable, and timely data to make sound public policy decisions and to evaluate their effects, we encountered considerable difficulty and gaps in assembling the necessary information. Based on our experience and the scholarly literature, we detail the problems and how scholars might address them in preparing reports on the local nonprofit sector. We conclude with recommendations to improve the collection, availability, and reliability of data on the nonprofit sector to guide public policy-making.
Is Federal Tax-Exemption Policy for Nonprofit Hospitals Moving to a Clearer Quid pro Quo Basis?
Authors: Longest Beaufort B.
Published: June 2012

The question of whether federal tax-exemption policy for nonprofit hospitals is moving to a clearer and more robust quid pro quo basis is examined. The question is important because heretofore the basis for federal exemption has been vague and fluid. Utilizing a quid pro quo rationale for federal tax-exemption of nonprofit hospitals as a framework, the chronological record of policy in this area is organized into three major periods: (1) A Simple Quid pro Quo: Early Federal Tax Policies for Nonprofit Hospitals; (2) A Changing Quid pro Quo: The Modern Era of Federal Tax Policy for Nonprofit Hospitals; and (3) An Emergent, Clearer Quid pro Quo: Recent Congressional Activism on Exemption Policy, including relevant provisions of the ACA. The article concludes with discussion of continuing vagueness and ambiguity in federal corporate income tax policy for nonprofit hospitals. The importance of enhanced clarity and specificity in the information upon which policy in this area is based is discussed, as are actions needed by Congress and the Internal Revenue Service to accomplish improved exemption policy.
Focal adhesion kinase-regulated signaling events in human cancer
Authors: Fu Wei , Hall Jessica E. , Schaller Michael D.
Published: June 2012

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that is highly expressed or activated in many human cancers. Under specific scenarios, FAK can regulate cell proliferation, cell survival, cell migration and invasion, and has been implicated in the control of tumorigenesis and metastasis. FAK has both catalytic and scaffolding activity, and triggers downstream signals by activation of a number of pathways, including the Ras/mitogen-activated protein kinase pathway, the phosphatidylinositol 3′-kinase/Akt pathway, and Rho family GTPases. Recent evidence also suggests novel signaling interactions between FAK and p53. These signaling events were defined primarily from studies on cells in culture, and elucidating which of these signaling pathways are pathologically relevant downstream of FAK in human cancer remains an important goal in determining the molecular mechanisms of tumorigenesis and metastasis. This review discusses select evidence of these signaling pathways with an emphasis on studies linking these to animal models of cancer and human disease. The role of FAK in the process of epithelial-to-mesenchymal transition and in cancer stem cells and recent therapeutic advances targeting FAK are also discussed.
High Integrated Microwave Architecture Using LTCC-SIP Technology in Active Phased Array Antenna Applications
Authors: Zhou Jun , Shi Wei , Dou Wen-Bin , Shen Ya
Published: June 2012

A kind of three dimensional Low Temperature Co-fired Ceramic (LTCC)-System in Package (SIP) transition was proposed in this paper. The basic design of SIP with LTCC technology was done by vertical transitions which transmit the microwave signal from the bottom to the surface of the substrate. The measured insertion loss did not exceed 1.5 dB, which contains the insertion loss of the test board about 0.6 dB at 18 GHz and the return loss was better than
Performance of the definitions of the systemic inflammatory response syndrome and sepsis in neonates
Authors: Hofer Nora , Zacharias Eva , Müller Wilhelm , Resch Bernhard
Published: June 2012

Aims: The aim of this study was to examine the applicability of the definitions of the systemic inflammatory response syndrome (SIRS) and sepsis to neonates during the first 3 days of life.

Methods: This is a retrospective study of all term neonates hospitalized within the first 24 h of life from 2004 to 2010 at our neonatal intensive care unit.

Results: Of 476 neonates, 30 (6%) had a diagnosis of culture-proven early-onset sepsis (EOS) and 81 (17%) had culture-negative clinical EOS or suspected EOS. SIRS and sepsis criteria were applied to 116 (24%) and 61 (13%) neonates, respectively. Of 30 neonates with culture proven, EOS 14 (53%) fulfilled SIRS and sepsis criteria. The single diagnostic criterion of SIRS applied to 20% (hypothermia or fever), 43% (white blood cell count/immature-to-total neutrophil ratio), 87% (respiratory symptoms), and 33% (cardiocirculatory symptoms) of all neonates with culture-proven EOS.

Conclusions: The definitions of SIRS and sepsis did not apply to about half of all cases of culture-proven EOS. An evidence-based approach to find the appropriate criteria for defining EOS in the neonate is needed.