bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bax/Mcl-1 balance affects neutrophil survival in intermittent hypoxia and obstructive sleep apnea: effects of p38MAPK and ERK1/2 signaling
Authors: Dyugovskaya Larissa , Polyakov Andrey , Cohen-Kaplan Victoria , Lavie Peretz , Lavie Lena 
Published: October 2012

AbstractBackgroundProlonged neutrophil survival is evident in various cardiovascular and respiratory morbidities, in hypoxic conditionsin-vitroand in patients with obstructive sleep apnea (OSA) characterized by nightly intermittent hypoxia (IH). This may lead to persistent inflammation, tissue injury and dysfunction. We therefore investigated by a translational approach the potential contribution of the intrinsic stress-induced mitochondrial pathway in extending neutrophil survival under IH conditions. Thus, neutrophils of healthy individuals treated with IHin-vitroand neutrophils of OSA patients undergoing nightly IH episodesin-vivowere investigated. Specifically, the balance between pro-apoptotic Bax and anti-apoptotic Mcl-1 protein expression, and the potential involvement of p38MAPK and ERK1/2 signaling pathways in the control of Mcl-1 expression were investigated.MethodsPurified neutrophils were exposed to IH and compared to normoxia and to sustained hypoxia (SH) using a BioSpherix-OxyCycler C42 system. Bax and Mcl-1 levels, and p38MAPK and ERK1/2 phosphorylation were determined by western blotting. Also, Bax/Mcl-1 expression and Bax translocation to the mitochondria were assessed by confocal microscopy in pre-apoptotic neutrophils, before the appearance of apoptotic morphology. Co-localization of Bax and mitochondria was quantified by LSM 510 CarlZeiss MicroImaging using Manders Overlap Coefficient. A paired two-tailedt test,with Bonferroni correction for multiple comparisons, was used for statistical analysis.ResultsCompared to normoxia, IH and SH up-regulated the anti-apoptotic Mcl-1 by about 2-fold, down-regulated the pro-apoptotic Bax by 41% and 27%, respectively, and inhibited Bax co-localization with mitochondria before visible morphological signs of apoptosis were noted. IH induced ERK1/2 and p38MAPKs phosphorylation, whereas SH induced only p38MAPK phosphorylation. Accordingly, both ERK and p38MAPK inhibitors attenuated the IH-induced Mcl-1 increase. In SH, only p38MAPK inhibition decreased Mcl-1 expression. Similar to neutrophils of healthy subjects exposed to IH (0.97± 0.2), in OSA neutrophils, Bax/Mcl-1 ratio was significantly lower compared to normoxic controls (1.0±0.5 vs.1.99±0.3, p=0.015), and Bax did not co-localize with mitochondria.ConclusionsThese findings suggest that decreased Bax/Mcl-1 balance promotes neutrophil survival in IHin-vitroas well as in OSA patients. Moreover, Bax/Mcl-1 protein function in IH and SH might be regulated by different signal transduction pathways, highlighting a novel regulatory function through ERK1/2 signaling in IH.
Stereophonic hands-free communication system based on microphone array fixed beamforming: real-time implementation and evaluation
Authors: Pirro Matteo , Squartini Stefano , Romoli Laura , Piazza Francesco 
Published: October 2012

Abstract
In this article, the authors propose an optimally designed fixed beamformer (BF) for stereophonic acoustic echo cancelation (SAEC) in real hands-free communication applications. Several contributions related to the combination of beamforming and echo cancelation have appeared in the literature so far, but, up to the authors’ knowledge, the idea of using optimal fixed BFs in a real-time SAEC system both for echo reduction and stereophonic audio rendering is first addressed in this contribution. The employment of such designed BFs allows positively addressing both issues, as the several simulated and real tests seem to confirm. In particular, the stereo-recording quality attainable through the proposed approach has been preliminarily evaluated by means of subjective listening tests. Moreover, the overall system robustness against microphone array imperfections and noise presence has been experimentally evaluated. This allowed the authors to implement a real hands-free communication system in which the usage of the proposed beamforming technique has proven its superiority with respect to the usual two-microphone one in terms of echo reduction, and guaranteeing a comparable spatial image. Moreover, the proposed framework requires a low computational cost increment with regard to the baseline approach, since only few extra filtering operations with short filters need to be executed. Nevertheless, according to the performed simulations, the BF-based SAEC configuration seems to not require the signal decorrelation module, resulting in an overall computational saving.
Effects of over-expression of TLR2 in transgenic goats on pathogen clearance and role of up-regulation of lysozyme secretion and infiltration of inflammatory cells
Authors: Deng Shoulong , Yu Kun , Zhang Baolu , Yao Yuchang , Liu Yufeng , He Haijuan , Zhang Hongtao , Cui Maosheng , Fu Juncai , Lian Zhengxing , Li Ning 
Published: October 2012

AbstractBackgroundToll-like receptor 2 (TLR2) is important to host recognition of invading gram-positive microbes. In goats, these microbes can cause serious mastitis, anthrax, tetanus, and other problems. Transgenic goats constitutively over-expressing TLR2 in many tissues serve as a suitable model for the study of the role of TLR2 over-expression in bacterial clearance.ResultsCapra hircusTLR2 over-expression vector (p3S-LoxP-TLR2) was used to generate transgenic goats by egg microinjection. The integration efficiency was 8.57%. Real-time PCR and immunohistochemical results confirmed that the goats over-expressing the TLR2 gene (Tg) expressed more TLR2 than wild-type goats (WT). Monocyte-macrophages from the bloodstreams of transgenic goats were stimulated with synthetic bacterial lipoprotein (Pam3CSK4) and by the promotion of interleukin-6 (IL-6) and IL-10 expression in vitro. The oxidative damage was significantly reduced, and lysozyme (LZM) secretion was found to be up-regulated. Ear tissue samples from transgenic goats that had been stimulated with Pam3CSK4 via hypodermic injection showed that transgenic individuals can undergo the inflammation response very quickly.ConclusionsOver-expression of TLR2 was found to decrease radical damage to host cells through low-level production of NO and MDA and to promote the clearance of invasive bacteria by up-regulating lysozyme secretion and filtration of inflammatory cells to the infected site.
The ASTUTE Health study protocol: Deliberative stakeholder engagements to inform implementation approaches to healthcare disinvestment
Authors: Watt Amber M , Hiller Janet E , Braunack-Mayer Annette J , Moss John R , Buchan Heather , Wale Janet , Riitano Dagmara E , Hodgetts Katherine , Street Jackie M , Elshaug Adam G ,   for the ASTUTE Health study group
Published: October 2012

Abstract

Background
Governments and other payers are yet to determine optimal processes by which to review the safety, effectiveness, and cost-effectiveness of technologies and procedures that are in active use within health systems, and rescind funding (partially or fully) from those that display poor profiles against these parameters. To further progress a disinvestment agenda, a model is required to support payers in implementing disinvestment in a transparent manner that may withstand challenge from vested interests and concerned citizens. Combining approaches from health technology assessment and deliberative democratic theory, this project seeks to determine if and how wide stakeholder engagement can contribute to improved decision-making processes, wherein the views of both vested and non-vested stakeholders are seen to contribute to informing policy implementation within a disinvestment context.

Methods/design
Systematic reviews pertaining to illustrative case studies were developed and formed the evidence base for discussion. Review findings were presented at a series of deliberative, evidence-informed stakeholder engagements, including partisan (clinicians and consumers) and non-partisan (representative community members) stakeholders. Participants were actively facilitated towards identifying shared and dissenting perspectives regarding public funding policy for each of the case studies and developing their own funding models in response to the evidence presented. Policy advisors will subsequently be invited to evaluate disinvestment options based on the scientific and colloquial evidence presented to them, and to explore the value of this information to their decision-making processes with reference to disinvestment.

Discussion
Analysis of the varied outputs of the deliberative engagements will contribute to the methodological development around how to best integrate scientific and colloquial evidence for consideration by policy advisors. It may contribute to the legitimization of broad and transparent stakeholder engagement in this context. It is anticipated that decision making will benefit from the knowledge delivered through informed deliberation with engaged stakeholders, and this will be explored through interviews with key decision makers.
Bone health in children with long–term idiopathic subclinical hypothyroidism
Authors: Di Mase Raffaella , Cerbone Manuela , Improda Nicola , Esposito Andrea , Capalbo Donatella , Mainolfi Ciro , Santamaria Francesca , Pignata Claudio , Salerno Mariacarolina 
Published: October 2012

AbstractBackgroundSubclinical hypothyroidism (SH) is a relatively common condition characterized by a mild persistent thyroid failure. The management of children with SH is still a controversial issue and the decision to treat with L-thyroxine represents a clinical dilemma. Thyroid hormone and TSH play an important role in skeletal growth and bone mineral homeostasis.AimTo evaluate whether untreated idiopathic SH may affect bone health in childhood and to compare two different diagnostic tools such as dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS).Patients and MethodsTwenty-five children and adolescents (11 males) aged 9.8 ± 3.5 years (range 4.2-18.7) with untreated idiopathic SH were enrolled in the study. SH was diagnosed on the basis of normal FT4 levels with TSH concentrations between 4.2 and 10 mU/l. Children have been followed for 3.3 ± 0.3 years from the time of SH diagnosis. Twenty-five healthy children, age- and sex-matched, were enrolled as controls. Patients and controls underwent DXA to evaluate lumbar spine bone mineral density (BMD) and QUS at proximal phalanges of the non-dominant hand to assess bone quality, measured as amplitude-dependent speed of sound (Ad-SoS) and bone transmission time (BTT).ResultsMean BMD Z-score was −0.4 ± 1.36 in patients and −0.2 ± 1.2 in controls. Mean Ad-SoS Z-score was 0.01 ± 1.0 in patients and 0.1 ± 1.2 in controls and mean BTT Z-score was −0.03 ± 0.8 and 0.04 ± 1.1 respectively. All values were within the normal range, both in patients and in controls. There were no statistically significant differences between the two groups.ConclusionBone health, evaluated by lumbar spine DXA and phalangeal QUS, is not impaired in our children, despite long-term duration of idiopathic SH. Data about bone status provided by QUS are comparable to those provided by DXA. Therefore, QUS may represent a good, cheaper and safe screening test for bone evaluation in children with SH.
Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer
Authors: Franken Bas , de Groot Marco R , Mastboom Walter JB , Vermes Istvan , van der Palen Job , Tibbe Arjan GJ , Terstappen Leon WMM 
Published: October 2012

Abstract
Introduction
The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether the presence of CTC at the time of diagnosis was associated with recurrence-free survival (RFS) and BRD.

Methods
In a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 602 patients before undergoing surgery for breast cancer. There were 97 patients with a benign tumor, 101 did not meet the inclusion criteria of which there were 48 patients with DCIS, leaving 404 stage I to III patients. Patients were stratified into unfavorable (CTC ≥1) and favorable (CTC = 0) prognostic groups.

Results
≥1 CTC in 30 ml blood was detected in 15 (15%) benign tumors, in 9 DCIS (19%), in 28 (16%) stage I, 32 (18%) stage II and in 16 (31%) patients with stage III. In stage I to III patients 76 (19%) had ≥1 CTC of whom 16 (21.1%) developed a recurrence. In 328 patients with 0 CTC 38 (11.6%) developed a recurrence. Four-year RFS was 88.4% for favorable CTC and 78.9% for unfavorable CTC (P = 0.038). A total of 25 patients died of breast cancer-related causes and 11 (44%) had ≥1 CTC. BRD was 4.3% for favorable and 14.5% for unfavorable CTC (P = 0.001). In multivariate analysis ≥1 CTC was associated with distant disease-free survival, but not for overall recurrence-free survival. CTC, progesterone receptor and N-stage were independent predictors of BRD in multivariate analysis.

Conclusions
Presence of CTC in breast cancer patients before undergoing surgery with curative intent is associated with an increased risk for breast cancer-related death.
Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland
Authors: Shehata Mona , Teschendorff Andrew , Sharp Gemma , Novcic Nikola , Russell I Alasdair , Avril Stefanie , Prater Michael , Eirew Peter , Caldas Carlos , Watson Christine J , Stingl John 
Published: October 2012

Abstract
Introduction
The organisation of the mammary epithelial hierarchy is poorly understood. Our hypothesis is that the luminal cell compartment is more complex than initially described, and that an understanding of the developmental relationships within this lineage will help in understanding the cellular context in which breast tumours occur.

Methods
We used fluorescence-activated cell sorting along with in vitro and in vivo functional assays to examine the growth and differentiation properties of distinct subsets of human and mouse mammary epithelial cells. We also examined how loss of steroid hormones influenced these populations in vivo. Gene expression profiles were also obtained for all the purified cell populations and correlated to those obtained from breast tumours.

Results
The luminal cell compartment of the mouse mammary gland can be resolved into nonclonogenic oestrogen receptor-positive (ER+) luminal cells, ER+ luminal progenitors and oestrogen receptor-negative (ER-) luminal progenitors. The ER+ luminal progenitors are unique in regard to cell survival, as they are relatively insensitive to loss of oestrogen and progesterone when compared with the other types of mammary epithelial cells. Analysis of normal human breast tissue reveals a similar hierarchical organisation composed of nonclonogenic luminal cells, and relatively differentiated (EpCAM+CD49f+ALDH-) and undifferentiated (EpCAM+CD49f+ALDH+) luminal progenitors. In addition, approximately one-quarter of human breast samples examined contained an additional population that had a distinct luminal progenitor phenotype, characterised by low expression of ERBB3 and low proliferative potential. Parent-progeny relationship experiments demonstrated that all luminal progenitor populations in both species are highly plastic and, at low frequencies, can generate progeny representing all mammary cell types. The ER- luminal progenitors in the mouse and the ALDH+ luminal progenitors in the human appear to be analogous populations since they both have gene signatures that are associated with alveolar differentiation and resemble those obtained from basal-like breast tumours.

Conclusion
The luminal cell compartment in the mammary epithelium is more heterogeneous than initially perceived since progenitors of varying levels of luminal cell differentiation and proliferative capacities can be identified. An understanding of these cells will be essential for understanding the origins and the cellular context of human breast tumours.
Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis
Authors: Adamzik Michael , Görlinger Klaus , Peters Jürgen , Hartmann Matthias 
Published: October 2012

Abstract
Introduction
Sepsis leads to an activation of the immune system and hemostatis. However, studies on platelet aggregation in severe sepsis using impedance aggregometry have not been performed and the diagnostic and prognostic capabilities are unknown. In the present study we hypothesized that impedance aggregometry findings might serve as a biomarker for the diagnosis and prognosis of severe sepsis.

Methods
Eighty patients with severe sepsis and 50 postoperative patients were included in the prospective observational study. Platelet function was determined at the first day of severe sepsis and surgery, respectively, using impedance aggregometry (Multiplate®). Moreover, platelet count, procalcitonin, interleukin 6, C-reactive protein and 30-day mortality were determined.

Results
Compared to postoperative patients, platelet aggregation was significantly reduced in patients with severe sepsis (collagen-test: 70.8 (44.4, 83.2) arbitrary units (A.U.) vs. 26.8 (12.7, 45.8) A.U.; P <0.001; median and quartiles). Furthermore, marked differences in platelet function were observed in survivors and non-survivors of severe sepsis (collagen-test: 33.4 (10.9, 48.8) A.U. vs. 12.4 (6.5, 25.0) A.U.; P = 0.001). Kaplan-Meier analysis demonstrated that higher platelet function was associated with a mortality of 10%, while mortality was 40% when platelet function was low (collagen-test; P = 0.002). The odds ratio was 6.0. In both univariate and multivariate analyses (including procalcitonin, IL6, C-reactive protein and platelet count) impedance aggregometry using collagen as the activator proved to be the best and an independent predictor for the diagnosis and prognosis of severe sepsis in critical illness.

Conclusions
In severe sepsis, impedance aggregometry allows better prediction of diagnosis and survival than conventional biomarkers and platelet count.
See related Letter by Hartmann et al.http://ccforum.com/content/17/2/427
Trade Unions and the ICFTU in the Age of Developmentalism in Brazil, 1953–1962
Authors: Colistete Renato P. 
Published: October 2012

Abstract
This article examines the relations between the International Confederation of Free Trade Unions (ICFTU) and its local allies in Brazil during the 1950s and early 1960s. Devised as a tool for uniting non-Communist trade unions worldwide, the ICFTU saw its influence limited by US labor policies toward Latin America and the conditions of labor politics in Brazil, contrary to what happened in Western Europe. The developments on both domestic and international fronts of organized labor had important implications for the political economy of growth and inequality, as the confrontational pattern of labor relations undermined the development of a social compact that could promote economic growth and social reform in postwar Brazil.
Dynamic conformal arc cranial stereotactic radiosurgery: implications of multileaf collimator margin on dose–volume metrics
Authors: Tanyi J A , Doss E J , Kato, C M , Monaco D L , ZMeng L , Chen Y , Kubicky C D , Marquez C M , Fuss M 
Published: October 2012

Objective
The effect of multileaf collimator (MLC) margin on target and normal tissue dose–volume metrics for intracranial stereotactic radiosurgery (SRS) was assessed.

Methods
118 intracranial lesions of 83 SRS patients formed the basis of this study. For each planning target volume (PTV), five separate treatment plans were generated with MLC margins of −1, 0, 1, 2 and 3 mm, respectively. Identical treatment planning parameters were employed with a median of five dynamic conformal arcs using the Varian/BrainLab high-definition MLC for beam shaping. Prescription dose (PD) was such that 22 Gy covered at least 95% of the PTV. Dose–volume and dose–response comparative metrics included conformity index, heterogeneity index, dose gradient, tumour control probability (TCP) and normal tissue complication probability (NTCP).

Results
Target dose heterogeneity decreased with increasing MLC margin (p&lt;0.001); mean heterogeneity index decreased from 70.4±12.7 to 10.4±2.2%. TCP decreased with increasing MLC margin (p&lt;0.001); mean TCP decreased from 81.0±2.3 to 62.2±1.8%. Normal tissue dose fall-off increased with MLC margin (p&lt;0.001); mean gradient increased from 3.1±0.9 mm to 5.3±0.7 mm. NTCP was optimal at 1 mm MLC margin. No unambiguous correlation was observed between NTCP and PTV volume. Plan delivery efficiency generally improved with larger margins (p&lt;0.001); mean monitor unit per centigray of the PD decreased from 3.60±1.30 to 1.56±0.13.

Conclusion
Use of 1 mm MLC margins for dynamic conformal arc-based cranial radiosurgery resulted in optimal tumour control and normal tissue sparing. Clinical significance of these comparative findings warrants further investigation.
Calcite distribution and orientation in the tergite exocuticle of the isopods Porcellio scaber and Armadillidium vulgare (Oniscidea, Crustacea)
Authors: Seidl Bastian H. M. , Reisecker Christian , Hild Sabine , Griesshaber Erika , Ziegler Andreas 
Published: October 2012

AbstractThe crustacean cuticle is a bio-composite consisting of hierarchically organized chitin-protein fibres, reinforced with calcite, amorphous calcium carbonate and phosphates. Comparative studies revealed that the structure and composition of tergite cuticle of terrestrial isopods is adapted to the habitat of the animals, and to their behavioural patterns to avoid predation. In this contribution we use FE-SEM, polarized SCμ-RSI and EBSD to investigate micro- and nano-patterns of mineral phase distribution and crystal orientation within the tergite cuticle of the two terrestrial isopod speciesArmadillidium vulgareandPorcellio scaber. The results show that the proximal regions of the exocuticle contain both calcite and ACC, with ACC located within the pore canals. Calcite forms hierarchically organised mesocrystalline aggregates of similar crystallographic orientation. Surprisingly,c-axis orientation preference is horizontal in regard to the local cuticle surface for both species, in contrast to mollusc and brachiopod shell structures in which thec-axis is always perpendicular to the shell surface. The overall sharpness of calcite crystal orientation is weak compared to that of mollusc shells. However, there are considerable differences in texture sharpness between the two isopod species. In the thick cuticle of the slow-walkingA. vulgarecalcite is more randomly oriented resulting in more isotropic mechanical properties of the cuticle. In contrast, the rather thin and more flexible cuticle of the fast- runningP. scabertexture sharpness is stronger with a preference ofc-axis orientation being parallel to the bilateral symmetry-plane of the animal, leading to more anisotropic mechanical properties of the cuticle. These differences may represent adaptations to different external and/or internal mechanical loads the cuticle has to resist during predatory attempts.