bluuebunny/crossref_metadata_2025 huggingface dataset:
Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib
Authors: Hughes Timothy P. , Saglio Giuseppe , Kantarjian Hagop M. , Guilhot François , Niederwieser Dietger , Rosti Gianantonio , Nakaseko Chiaki , De Souza Carmino Antonio , Kalaycio Matt E. , Meier Stephan , Fan Xiaolin , Menssen Hans D. , Larson Richard A. , Hochhaus Andreas
Published: December 2013

Key Points

More patients with chronic myeloid leukemia in chronic phase achieve EMR on frontline nilotinib than imatinib. EMR failure on frontline nilotinib or imatinib predicts poor outcomes in patients with chronic myeloid leukemia in chronic phase.
Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenström's macroglobulinemia
Authors: Hodge Lucy S. , Ziesmer Steven C. , Yang Zhi-Zhang , Secreto Frank J. , Novak Anne J. , Ansell Stephen M.
Published: December 2013

Key Points

STAT5 is constitutively phosphorylated in malignant B cells obtained from patients with Waldenström's macroglobulinemia. Inhibition of STAT5 signaling significantly decreases IgM production and may be useful therapeutically for patients with high IgM levels.
Results of an open-label multicenter phase 2 trial of lenalidomide monotherapy in refractory mycosis fungoides and Sézary syndrome
Authors: Querfeld Christiane , Rosen Steven T. , Guitart Joan , Duvic Madeleine , Kim Youn H. , Dusza Stephen W. , Kuzel Timothy M.
Published: December 2013

Key Points

Lenalidomide is effective in refractory advanced cutaneous T-cell lymphoma, with an overall response rate of 28%. Patients demonstrate a transient flare reaction in skin, blood, and/or lymph nodes that may be associated with improvement in disease burden.
Gene set bagging for estimating the probability a statistically significant result will replicate
Authors: Jaffe Andrew E , Storey John D , Ji Hongkai , Leek Jeffrey T
Published: December 2013

Background

Significance analysis plays a major role in identifying and ranking genes, transcription factor binding sites, DNA methylation regions, and other high-throughput features associated with illness. We propose a new approach, called gene set bagging, for measuring the probability that a gene set replicates in future studies. Gene set bagging involves resampling the original high-throughput data, performing gene-set analysis on the resampled data, and confirming that biological categories replicate in the bagged samples.

Results

Using both simulated and publicly-available genomics data, we demonstrate that significant categories in a gene set enrichment analysis may be unstable when subjected to resampling. We show our method estimates the replication probability (R), the probability that a gene set will replicate as a significant result in future studies, and show in simulations that this method reflects replication better than each set’s p-value.

Conclusions

Our results suggest that gene lists based on p-values are not necessarily stable, and therefore additional steps like gene set bagging may improve biological inference on gene sets.
c-Jun N-terminal kinase in synergistic neurite outgrowth in PC12 cells mediated through P90RSK
Authors: Seow Kok Huei , Zhou Lihan , Stephanopoulos Gregory , Too Heng-Phon
Published: December 2013

Background

Synergistic multi-ligand treatments that can induce neuronal differentiation offer valuable strategies to regulate and modulate neurite outgrowth. Whereas the signaling pathways mediating single ligand-induced neurite outgrowth, such as Akt, extracellular signal-regulated kinase (Erk), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (P38), have been extensively studied, the mechanisms underlying multi-ligand synergistic neurite outgrowth are poorly understood. In an attempt to gain insight into synergistic neurite outgrowth, PC12 cells were treated with one of three combinations: pituitary adenylate cyclase-activating peptide (PACAP) with epidermal growth factor (EP), basic fibroblast growth factor (FP), or nerve growth factor (NP) and then challenged with the appropriate kinase inhibitors to assess the signaling pathways involved in the process.

Results

Response surface analyses indicated that synergistic neurite outgrowth was regulated by distinct pathways in these systems. Synergistic increases in the phosphorylation of Erk and JNK, but not Akt or P38, were observed with the three growth factor-PACAP combinations. Unexpectedly, we identified a synergistic increase in JNK phosphorylation, which was involved in neurite outgrowth in the NP and FP, but not EP, systems. Inhibition of JNK using the SP600125 inhibitor reduced phosphorylation of 90 kDa ribosomal S6 kinase (P90RSK) in the NP and FP, but not EP, systems. This suggested the involvement of P90RSK in mediating the differential effects of JNK in synergistic neurite outgrowth.

Conclusions

Taken together, these findings reveal the involvement of distinct signaling pathways in regulating neurite outgrowth in response to different synergistic growth factor-PACAP treatments. Our findings demonstrate a hitherto unrecognized mechanism of JNK-P90RSK in mediating synergistic neurite outgrowth induced by the co-treatment of growth factors and PACAP.
Trastuzumab mediates antibody-dependent cell-mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients
Authors: Petricevic Branka , Laengle Johannes , Singer Josef , Sachet Monika , Fazekas Judit , Steger Guenther , Bartsch Rupert , Jensen-Jarolim Erika , Bergmann Michael
Published: December 2013

Background

Monoclonal antibodies (mAb), such as trastuzumab are a valuable addition to breast cancer therapy. Data obtained from neoadjuvant settings revealed that antibody-dependent cell-mediated cytotoxicity (ADCC) is a major mechanism of action for the mAb trastuzumab. Conflicting results still call into question whether disease progression, prolonged treatment or concomitant chemotherapy influences ADCC and related immunological phenomena.

Methods

We analyzed the activity of ADCC and antibody-dependent cell-mediated phagocytosis (ADCP) of peripheral blood mononuclear cells (PBMCs) from human epidermal growth factor receptor 2 (HER2/neu) positive breast cancer patients receiving trastuzumab therapy either in an adjuvant (n = 13) or metastatic (n = 15) setting as well as from trastuzumab treatment-naive (t-naive) HER2/neu negative patients (n = 15). PBMCs from healthy volunteers (n = 24) were used as controls. ADCC and ADCP activity was correlated with the expression of antibody binding Fc-gamma receptor (FcγR)I (CD64), FcγRII (CD32) and FcγRIII (CD16) on CD14+ (monocytes) and CD56+ (NK) cells, as well as the expression of CD107a+ (LAMP-1) on CD56+ cells and the total amount of CD4+CD25+FOXP3+ (Treg) cells. In metastatic patients, markers were correlated with progression-free survival (PFS).

Results

ADCC activity was significantly down regulated in metastatic, adjuvant and t-naive patient cohorts as compared to healthy controls. Reduced ADCC activity was inversely correlated with the expression of CD107a on CD56+ cells in adjuvant patients. ADCC and ADCP activity of the patient cohorts were similar, regardless of treatment duration or additional chemotherapy. PFS in metastatic patients inversely correlated with the number of peripheral Tregcells.

Conclusion

The reduction of ADCC in patients as compared to healthy controls calls for adjuvant strategies, such as immune-enhancing agents, to improve the activity of trastuzumab. However, efficacy of trastuzumab-specific ADCC and ADCP appears not to be affected by treatment duration, disease progression or concomitant chemotherapy. This finding supports the application of trastuzumab at any stage of the disease.
Performance analysis of interference-limited dual-hop multiple antenna AF relaying systems with feedback delay
Authors: Wang Jinlong , Huang Yuzhen , Zhong Caijun , Al-Qahtani Fawaz , Wu Qihui , Cheng Yunpeng
Published: December 2013

In this paper, we present a comprehensive performance analysis of dual-hop multiple antenna channel state information (CSI) assisted amplify-and-forward (AF) relaying systems over Rayleigh fading channels employing arbitrary transmit antenna selection (TAS) and receiver maximum ratio combining (MRC) with feedback delay in the presence of co-channel interference (CCI) at both the relay and destination. Specifically, an upper bound on the cumulative distribution function (CDF) of the end-to-end signal-to-interference ratio (SIR) is proposed, based on which closed-form expressions for the outage probability and the average symbol error rate (SER) are derived. To gain further insights, simple and high informative expressions for the outage probability and the average SER are obtained at the high SIR regime, which readily enable us to characterize the achievable diversity order and coding gain of the system. Moreover, we present new analytical upper and lower bounds for the ergodic capacity of the system, which apply to the system with arbitrary number of antennas, CCI and feedback delay at any SIRs. Finally, to minimize the outage probability of the system, an optimum power allocation scheme is devised under the total transmission power constraint between the source and the relay. The findings suggest that the feedback delay limits the diversity order to one, while the CCI degrades the outage performance by affecting the coding gain of the system.
Existence and multiplicity of positive bound states for Schrödinger equations
Authors: Sheng Sun , Wang Fanglei , An Tianqing
Published: December 2013

In this paper, we study the existence and multiplicity of positive bound states of non-autonomous systems of nonlinear Schrödinger equations. The proof is based on the fixed point theorems in a cone.

MSC:34B15, 35J20.
Evaluating larval mosquito resource partitioning in western Kenya using stable isotopes of carbon and nitrogen
Authors: Gilbreath Thomas M , Kweka Eliningaya J , Afrane Yaw A , Githeko Andrew K , Yan Guiyun
Published: December 2013

Background

In sub-Saharan Africa, malaria, transmitted by the Anopheles mosquito, remains one of the foremost public health concerns. Anopheles gambiae, the primary malaria vector in sub-Saharan Africa, is typically associated with ephemeral, sunlit habitats; however, An. gambiae larvae often share these habitats with other anophelines along with other disease-transmitting and benign mosquito species. Resource limitations within habitats can constrain larval density and development, and this drives competitive interactions among and between species.

Methods

We used naturally occurring stable isotope ratios of carbon and nitrogen to identify resource partitioning among co-occurring larval species in microcosms and natural habitats in western Kenya. We used two and three source mixing models to estimate resource utilization (i.e. bacteria, algae, organic matter) by larvae.

Results

Laboratory experiments revealed larval δ13C and δ15N composition to reflect the food sources they were reared on. Resource partitioning was demonstrated between An. gambiae and Culex quinquefasciatus larvae sharing the same microcosms. Differences in larval δ13C and δ15N content was also evident in natural habitats, and Anopheles species were consistently more enriched in δ13C when compared to culicine larvae.

Conclusions

These observations demonstrate inter-specific resource partitioning between Cx. quinquefasciatus and An. gambiae larvae in natural habitats in western Kenya. This information may be translated into opportunities for targeted larval control efforts by limiting specific larval food resources, or through bio-control utilizing competitors at the same trophic level.
Role of Androgens in Sex Differences in Cardiac Damage During Myocardial Infarction
Authors: Le Thi Y. L. , Ashton Anthony W. , Mardini Mahidi , Stanton Peter G. , Funder John W. , Handelsman David J. , Mihailidou Anastasia S.
Published: December 2013

Age-specific incidence of ischemic heart disease in men is higher than in women, although women die more frequently without previous symptoms; the molecular mechanism(s) are poorly understood. Most studies focus on protection by estrogen, with less attention on androgen receptor-mediated androgen actions. Our aim was to determine the role of androgens in the sex differences in cardiac damage during myocardial infarction. Mature age-matched male and female Sprague Dawley rats, intact or surgically gonadectomized (Gx), received testosterone (T) or 17β-estradiol (E2) via subdermal SILASTIC (Dow Corning Corp.) implants; a subset of male rats received dihydrotestosterone. After 21 days, animals were anesthetized, and hearts were excised and subjected to ex vivo regional ischemia-reperfusion (I-R). Hearts from intact males had larger infarcts than those from females following I-R; Gx produced the opposite effect, confirming a role for sex steroids. In Gx males, androgens (dihydrotestosterone, T) and E2 aggravated I-R-induced cardiac damage, whereas in Gx females, T had no effect and E2 reduced infarct area. Increased circulating T levels up-regulated androgen receptor and receptor for advanced glycation end products, which resulted in enhanced apoptosis aggravating cardiac damage in both males and females. In conclusion, our study demonstrates, for the first time, that sex steroids regulate autophagy during myocardial infarction and shows that a novel mechanism of action for androgens during I-R is down-regulation of antiapoptotic protein Bcl-xL (B cell lymphoma-extra large), a key controller for cross talk between autophagy and apoptosis, shifting the balance toward apoptosis and leading to aggravated cardiac damage.
Recovery of Endocrine and Inflammatory Mediators Following an Extended Energy Deficit
Authors: Henning Paul C. , Scofield Dennis E. , Spiering Barry A. , Staab Jeffery S. , Matheny Ronald W. , Smith Martha A. , Bhasin Shalender , Nindl Bradley C.
Published: December 2013

Context:

Due to current operational requirements, elite soldiers deploy quickly after completing arduous training courses. Therefore, it is imperative that endocrine and inflammatory mediators have fully recovered.

Objective:

Our objective was to determine whether a short-term (2–6 wk) recovery period was sufficient to restore endocrine and inflammatory homeostasis after sustained energy deficit.

Design:

Before and immediately after the course, serum concentrations of inflammatory and endocrine markers were taken along with anthropometric measures prior to and immediately after the Army Ranger course. In addition, nine soldiers were assessed between 2 and 6 weeks after the course.

Setting:

This research occurred in a field setting during an intensive 8-week military training course characterized by high-energy expenditure, energy restriction, and sleep deprivation (U.S. Army Ranger School).

Participants:

Twenty-three male soldiers (23.0 ± 2.8 y; 177.6 ± 7.9 cm; 81.0 ± 9.6 kg, 16.8 ± 3.9% body fat) participated in this study.

Interventions:

There were no interventions used in this research.

Outcome Measures and Results:

Significant changes occurred in circulating total testosterone (−70%), brain-derived neurotrophic factor (−33%), total IGF-1 (−38.7%), free IGF-1 (−41%), IGF binding protein (IGFBP-6; −23.4%), sex-hormone binding globulin (+46%), thyroid stimulating hormone (+85%), IGFBP-1 (+534.4%), IGFBP-2 (+98.3%), IGFBP-3 (+14.7%), IL-4 (+135%), IL-6 (+217%), and IL-8 (+101%). Significant changes in body mass (−8%), bicep (−14%), forearm (−5%), thigh (−7%), and calf (−2%) circumferences, sum of skinfolds (−52%), and percentage body fat (−54%). All anthropometric, inflammatory, and hormonal values, except T3, were restored to baseline levels within 2–6 weeks after the course.

Conclusions:

Endocrine markers and anthropometric measures were degraded, and inflammatory mediators increased after an extended energy deficit. A short-term recovery of 2–6 weeks was sufficient to restore these mediators.
Semi-Infinite Paths of the Two-Dimensional Radial Spanning Tree
Authors: Baccelli François , Coupier David , Tran Viet Chi
Published: December 2013

We study semi-infinite paths of the radial spanning tree (RST) of a Poisson point process in the plane. We first show that the expectation of the number of intersection points between semi-infinite paths and the sphere with radius r grows sublinearly with r. Then we prove that in each (deterministic) direction there exists, with probability 1, a unique semi-infinite path, framed by an infinite number of other semi-infinite paths of close asymptotic directions. The set of (random) directions in which there is more than one semi-infinite path is dense in [0, 2π). It corresponds to possible asymptotic directions of competition interfaces. We show that the RST can be decomposed into at most five infinite subtrees directly connected to the root. The interfaces separating these subtrees are studied and simulations are provided.
Optimal Stopping Rule for the No-Information Duration Problem with Random Horizon
Authors: Tamaki Mitsushi
Published: December 2013

As a version of the secretary problem, Ferguson, Hardwick and Tamaki (1992) considered an optimal stopping problem called the duration problem. The basic duration problem is the classical duration problem, in which the objective is to maximize the time of possession of a relatively best object when a known number of rankable objects appear in random order. In this paper we generalize this classical problem in two directions by allowing the number N (of available objects) to be a random variable with a known upper bound n and also allowing the objects to appear in accordance with Bernoulli trials. Two models can be considered for our random horizon duration problem according to whether the planning horizon is N or n. Since the form of the optimal rule is in general complicated, our main concern is to give to each model a sufficient condition for the optimal rule to be simple. For N having a uniform, generalized uniform, or curtailed geometric distribution, the optimal rule is shown to be simple in the so-called secretary case. The asymptotic results, as n → ∞, will also be given for these priors.
Extinction Probabilities of Branching Processes with Countably Infinitely Many Types
Authors: Hautphenne S. , Latouche G. , Nguyen G.
Published: December 2013

We present two iterative methods for computing the global and partial extinction probability vectors for Galton-Watson processes with countably infinitely many types. The probabilistic interpretation of these methods involves truncated Galton-Watson processes with finite sets of types and modified progeny generating functions. In addition, we discuss the connection of the convergence norm of the mean progeny matrix with extinction criteria. Finally, we give a sufficient condition for a population to become extinct almost surely even though its population size explodes on the average, which is impossible in a branching process with finitely many types. We conclude with some numerical illustrations for our algorithmic methods.
Stochastic Sequences with a Regenerative Structure that May Depend Both on the Future and on the Past
Authors: Foss Sergey , Zachary Stan
Published: December 2013

Many regenerative arguments in stochastic processes use random times which are akin to stopping times, but which are determined by the future as well as the past behaviour of the process of interest. Such arguments based on ‘conditioning on the future’ are usually developed in an ad-hoc way in the context of the application under consideration, thereby obscuring the underlying structure. In this paper we give a simple, unified, and more general treatment of such conditioning theory. We further give a number of novel applications to various particle system models, in particular to various flavours of contact processes and to infinite-bin models. We give a number of new results for existing and new models. We further make connections with the theory of Harris ergodicity.
A Generalized Telegraph Process with Velocity Driven by Random Trials
Authors: Crimaldi Irene , Di Crescenzo Antonio , Iuliano Antonella , Martinucci Barbara
Published: December 2013

We consider a random trial-based telegraph process, which describes a motion on the real line with two constant velocities along opposite directions. At each epoch of the underlying counting process the new velocity is determined by the outcome of a random trial. Two schemes are taken into account: Bernoulli trials and classical Pólya urn trials. We investigate the probability law of the process and the mean of the velocity of the moving particle. We finally discuss two cases of interest: (i) the case of Bernoulli trials and intertimes having exponential distributions with linear rates (in which, interestingly, the process exhibits a logistic stationary density with nonzero mean), and (ii) the case of Pólya trials and intertimes having first gamma and then exponential distributions with constant rates.
Translocating myonuclei have distinct leading and lagging edges that require Kinesin and Dynein
Authors: Folker Eric S. , Schulman Victoria K. , Baylies Mary K.
Published: December 2013

Nuclei are precisely positioned within all cells, and mispositioned nuclei are a hallmark of many muscle diseases. Myonuclear positioning is dependent on Kinesin and Dynein, but interactions between these motor proteins and their mechanisms of action are unclear. We find that in developing Drosophila muscles, Dynein and Kinesin work together to move nuclei in a single direction by two separate mechanisms that are spatially segregated. First, the two motors work together in a sequential pathway that acts from the cell cortex at the muscle poles. This mechanism requires Kinesin-dependent localization of Dynein to cell cortex near the muscle pole. From this location Dynein can pull microtubule minus-ends and the attached myonuclei toward the muscle pole. Second, the motors exert forces directly on individual nuclei independently of the cortical pathway. However, the activities of the two motors on the nucleus are polarized relative to the direction of myonuclear translocation: Kinesin acts at the leading edge of the nucleus, whereas Dynein acts at the lagging edge of the nucleus. Consistent with the activities of Kinesin and Dynein being polarized on the nucleus, nuclei rarely change direction, and those that do, reorient to maintain the same leading edge. Conversely, nuclei in both Kinesin and Dynein mutant embryos change direction more often and do not maintain the same leading edge when changing directions. These data implicate Kinesin and Dynein in two distinct and independently regulated mechanisms of moving myonuclei, which together maximize the ability of myonuclei to achieve their proper localizations within the constraints imposed by embryonic development.
Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics: Drosophila as a model to study nephropathies
Authors: Tutor Antonio S. , Prieto-Sánchez Silvia , Ruiz-Gómez Mar
Published: December 2013

Drosophila nephrocytes are functionally homologous to vertebrate kidney podocytes. Both share the presence of slit diaphragms that function as molecular filters during the process of blood and haemolymph ultrafiltration. The protein components of the slit diaphragm are likewise conserved between flies and humans, but the mechanisms that regulate slit diaphragm dynamics in response to injury or nutritional changes are still poorly characterised. Here, we show that Dumbfounded/Neph1, a key diaphragm constituent, is a target of the Src kinase Src64B. Loss of Src64B activity leads to a reduction in the number of diaphragms, and this effect is in part mediated by loss of Dumbfounded/Neph1 tyrosine phosphorylation. The phosphorylation of Duf by Src64B, in turn, regulates Duf association with the actin regulator Dock. We also find that diaphragm damage induced by administration of the drug puromycin aminonucleoside (PAN model) directly associates with Src64B hyperactivation, suggesting that diaphragm stability is controlled by Src-dependent phosphorylation of diaphragm components. Our findings indicate that the balance between diaphragm damage and repair is controlled by Src-dependent phosphorylation of diaphragm components, and point to Src family kinases as novel targets for the development of pharmacological therapies for the treatment of kidney diseases that affect the function of the glomerular filtration barrier.
POPX2 phosphatase regulates the KIF3 kinesin motor complex
Authors: Phang Hui-Qun , Hoon Jing-Ling , Lai Soak Kuan , Zeng Yukai , Chiam Keng-Hwee , Li Hoi Yeung , Koh Cheng-Gee
Published: December 2013

The kinesin motors are important in the regulation of cellular functions such as protein trafficking, spindle organization and centrosome separation. In this study, we have identified POPX2, a serine-threonine phosphatase, as an interacting partner of the KAP3 subunit of the kinesin-2 motor. The kinesin-2 motor is a heterotrimeric complex composed of KIF3A, KIF3B motor subunits and KAP3, the non-motor subunit, which binds the cargo. Here we report that the phosphatase POPX2 is a negative regulator of the trafficking of N-cadherin and other cargoes; consequently, it markedly influences cell-cell adhesion. POPX2 affects trafficking by determining the phosphorylation status of KIF3A at serine-690. This is consistent with the observation that KIF3A-S690A mutant is defective in cargo trafficking. Our studies also implicate CaMKII as the kinase that phosphorylates KIF3A at serine-690. These results strongly suggest POPX2 and CaMKII as the phosphatase-kinase pair that regulates kinesin-mediated transport and cell-cell adhesion.
Mitochondrial ATP synthases cluster as discrete domains that reorganize with the cellular demand for oxidative phosphorylation
Authors: Jimenez Laure , Laporte Damien , Duvezin-Caubet Stephane , Courtout Fabien , Sagot Isabelle
Published: December 2013

Mitochondria are double membrane-bounded organelles that form a dynamic tubular network. Mitochondria energetic functions depend on a complex internal architecture. Cristae, inner membrane invaginations that folds into the matrix space, are proposed to be the site of oxidative phosphorylation (OXPHOS), reactions by which ATP synthase produces ATP. ATP synthase is also thought to have a role in cristae morphogenesis. To date, the exploration of the processes regulating mitochondrial internal compartmentalization have been mostly limited to electron microscopy. Here, we describe ATP synthase localization in living yeast cells and show that it clusters as discrete inner membrane domains. These domains are dynamic within the mitochondrial network. They are impaired in mutants defective in cristae morphology and partially overlap with the cristae-associated MICOS/MINOS/MITOS complex. Finally, ATP synthase occupancy increases with the cellular demand for OXPHOS. Overall our data suggest that domains in which ATP synthases are clustered correspond to mitochondrial cristae. Being able to follow mitochondria sub-compartments in living yeast cells opens new avenues to explore the mechanisms involved in inner membrane remodelling, an architectural feature crucial for mitochondrial activities.
Bora and Aurora-A continue to activate Plk1 in mitosis
Authors: Bruinsma Wytse , Macůrek Libor , Freire Raimundo , Lindqvist Arne , Medema René H.
Published: December 2013

Polo-like kinase-1 (Plk1) is required for proper cell division. Activation of Plk1 requires phosphorylation on a conserved threonine in the T-loop of the kinase domain (T210). Plk1 is first phosphorylated on T210 in G2 phase by the kinase Aurora-A, in concert with its cofactor Bora. However, Bora was shown to be degraded prior to entry into mitosis, and it is currently unclear how Plk1 activity is sustained in mitosis. Here we show that the Bora/Aurora-A complex remains the major activator of Plk1 in mitosis. We show that a small amount of Aurora-A activity is sufficient to phosphorylate and activate Plk1 in mitosis. In addition, a fraction of Bora is retained in mitosis, which is essential for continued Aurora-A dependent T210 phosphorylation of Plk1. We find that once Plk1 is activated, minimal amounts of the Bora/Aurora-A complex are sufficient to sustain Plk1 activity. Thus, the activation of Plk1 by Aurora-A may function as a bistable switch; highly sensitive to inhibition of Aurora-A in its initial activation, but refractory to fluctuations in Aurora-A activity once Plk1 is fully activated. This provides a cell with robust Plk1 activity once it has committed to mitosis.
Foundations of Constitutional Legal Responsibility in the Field of Normative Control
Authors: Yaroshenko Natalya
Published: December 2013

The author´s concept “constitutional delict” of the compliance assessment sphere is given, bases of realization of constitutional and legal responsibility are considered, problems of attraction to constitutional and legal responsibility in Russia are revealed.
Legal Basis of Non-Union Employee Representation in Germany
Authors: Plamennova Kristina
Published: December 2013

In the article experience of production councils in Germany in which the idea of not trade-union representation received the widest embodiment is analyzed.
Placental chorioangioma: literature review
Authors: Fan Miaoying , Skupski Daniel W.
Published: December 2013

Placental chorioangioma is the most common benign non-trophoblastic tumor of the placenta. It is derived from primitive chorionic mesenchyme and is typically vascular. Placenta chorioangiomas occur in approximately 1% of pregnancies. Most placental chorioangiomas are small and are not clinically important. However, those measuring more than 4–5 cm in diameter may be associated with maternal and fetal complications. Early diagnosis, close prenatal surveillance and appropriate intervention may prevent severe complications and perinatal mortality caused by chorioangioma. Here we review the incidence, prenatal diagnosis, complications, the pathophysiological mechanisms of maternal and fetal complications, and the therapeutic possibilities in pregnancies complicated by placental chorioangiomas.
Mother knows best? Comparing primiparous parturients’ expectations and predictions with actual birth outcomes
Authors: Bar-On Shikma , Benyamini Yael , Ebrahimoff Mindy , Many Ariel
Published: December 2013

Objective: The literature provides no clear evidence linking maternal optimism/pessimism to birth outcomes. Our objective was to determine whether maternal expectations and predictions regarding mode of delivery and epidural anesthesia aligned with birth outcomes.

Methods: Primiparous, low-risk pregnant women at term filled in questionnaires in which they rated their chances of a vaginal delivery (VD) or a cesarean section (CS), and their intention to receive epidural anesthesia. Their responses were compared to actual outcomes.

Results: Pre-birth perceptions of odds of delivery by a CS were significantly higher (P=0.04) among women who eventually had a vacuum extraction (VE) or CS as a result of an arrest disorder, compared with women who had a VD and those who had a CS or a VE due to non-reassuring fetal heart monitor. Intention to receive epidural anesthesia was significantly lower (P<0.001) among women who gave birth without it.

Conclusion: The pessimistic pre-birth perceptions of women of high odds for a CS may be related to an increased risk of arrest disorders of labor. However, the prenatal assessments of primiparous women are poor predictors of their demand for epidural anesthesia during labor. Larger-scale studies to determine whether pre-partum psychological interventions may contribute to the process of labor and improve obstetric outcomes are warranted
Experimental and numerical investigation in failure of cracked aluminum plates repaired with bonded FML composite patch, under impact loading
Authors: Vanani Lotfali Mozafari , Kashani Hamed Moayeri , Anaraki Ali Pourkamali , Ghasemi Faramarz Ashenai
Published: December 2013

In this paper, Charpy impact tests were conducted on cracked aluminum plates repaired with FML composite patches. The effects of the crack characteristics and patch lay-up sequence on the energy absorption of the specimens were investigated experimentally. In order to reduce the test numbers, the design of experiments method was used, and the results were predicted by response surface method. The effect of repairing on the fracture parameters [stress intensity factor (SIF), J-integral, and crack propagation direction (CPD)] at the crack front was calculated using three-dimensional (3D) finite element analysis. The results show that the value of the energy absorption increases when the crack angle increases and that the patch lay-up sequence has a significant role on the efficiency of the repair. When the location of the metal layer of the patch is near the repaired surface of the specimen, the value of the energy absorption increases.
Comparison of synchronisation and fertility after different modifications of the ovsynch protocol in cyclic dairy cows
Authors: Yilmazbas-Mecitoglu Gulnaz , Karakaya Ebru , Keskin Abdulkadir , Gumen Ahmet , Koc Volkan , Okut Hayrettin
Published: December 2013

The objectives of this study were to evaluate the effects of (1) double doses of PGF2α administration or (2) an exogenous progesterone (CIDR) applied concurrently with, or (3) the day after, first GnRH of Ovsynch (GnRH-1), on synchronisation and fertility during the Ovsynch protocol. All cows (n = 378) received the Ovsynch protocol (GnRH-7d-PGF2α-56h-GnRH-18h-TAI). The ‘OVS’ group (n = 105) received only the Ovsynch protocol. The ‘OVS-PGF’ group (n = 118, GnRH-7d-PGF2α-12h-PGF2α-44h-GnRH-18h-TAI) received an extra dose of PGF2α 12 h later on Day 7. The ‘OVS-7CIDR’ group (n = 78, GnRH+CIDR-7d-PGF2α-56h-GnRH-18h-TAI) received a CIDR for 7 days between GnRH-1 and PGF2α. In the ‘OVS-6CIDR’ group (n = 77, GnRH-24h-CIDR-6d-PGF2α-56h-GnRH-18h-TAI), CIDR was applied one day after GnRH-1 and removed 6 days later. When all cows were evaluated, the responses to GnRH-2 were higher (P = 0.005) in cows that responded to GnRH-1 (95.4%) compared to the cows that did not respond (87.6%). The pregnancy rates at 31 and 62 days for each group were 48.6% and 42.9% in the OVS, 54.2% and 52.5% in the OVS-PGF, 52.6% and 48.7% in the OVS-7CIDR, and 55.8% and 49.3% in the OVS-6CIDR groups. Thus, none of the three different treatments has an effect on increasing the out-comes of the Ovsynch protocol in cyclic lactating dairy cows.
Characterisation of Pseudomonas aeruginosa related to bovine mastitis
Authors: Park Hye , Hong Min , Hwang Sun , Park Young , Kwon Ka , Yoon Jang , Shin Sook , Kim Jae , Park Yong
Published: December 2013

Pseudomonas aeruginosa is one of the causative pathogens of bovine mastitis. Most P. aeruginosa strains possess the type III secretion system (TTSS), which may increase somatic cell counts (SCCs) in milk from mastitis-affected cows. Moreover, most of P. aeruginosa cells can form biofilms, thereby reducing antibiotic efficacy. In this study, the presence and effect of TTSS-related genotypes on increase of SCCs among 122 P. aeruginosa isolates obtained from raw milk samples from mastitis-affected cows and their antibiotic susceptibility at planktonic and biofilm status were investigated. Based on the presence of TTSS-related genes a total of 82.7% of the isolates were found to harbour exoU and/or exoS genes, including the invasive (exoU-/exoS+, 69.4%), cytotoxic (exoU+/exoS-, 8.3%) and cytotoxic/invasive strains (exoU+/ exoS+, 5.0%). Milk containing exoS-positive isolates had higher SCCs than those containing exoS-negative isolates. The majority of isolates showed gentamicin, amikacin, meropenem and ciprofloxacin susceptibility at planktonic status. However, the susceptibility was decreased at the biofilm status. Based on minimum biofilm eradication concentration (MBEC)/minimum inhibitory concentration (MIC) ratios, the range of change in antibiotic susceptibility varied widely depending on the antibiotics (from ≥ 3.1-fold to ≥ 475.0-fold). In conclusion, most P. aeruginosa isolates studied here had a genotype related to increase in SCCs. The efficiency of antibiotic therapy against P. aeruginosa-related bovine mastitis could be improved by analysing both the MBEC and the MIC of isolates.
A comparison of the concentrations of energy-balance-related variables in jugular and mammary vein blood of dairy cows with different milk yield
Authors: Šamanc Horea , Kirovski Danijela , Lakić Nada , Celeska Irena , Bojković-Kovačević Slavica , Sladojević Željko , Ivanov Ivan
Published: December 2013

The aim of this study was to compare the concentrations of blood variables obtained simultaneously from the jugular and mammary veins of dairy cows. Eighty Holstein cows were divided into four equal groups: dry, low- (LY), medium- (MY) and high-yielding (HY). Blood insulin, glucose, non-esterified fatty acid (NEFA), beta-hydroxybutyrate (BHBA) and urea concentrations were measured. The jugular and mammary vein (J/M) ratio between concentrations of each variable was calculated. Differences between the groups of cows in concentrations of variables in the jugular vein were not in accordance with those obtained for the mammary vein. J/M values for insulin and glucose concentrations were above 1.0 in all groups of cows. The ratios for NEFA and BHBA concentrations were under or equal to 1.0 in dry and LY cows but above 1.0 in the MY and HY groups, indicating that in MY and HY cows those metabolites are apparently utilised by the mammary gland. J/M values for urea were above 1.0 in dry and LY cows but less than 1.0 in groups MY and HY, indicating that in the latter case urea is apparently released by the mammary gland. In conclusion, J/M for NEFA, BHBA and urea may be useful for estimation of the critical point when the mammary gland receives insufficient energy precursors for its current activity.
Body fat distribution and metabolic consequences — Examination opportunities in dogs
Authors: Müller Linda , Kollár Eszter , Balogh Lajos , Pöstényi Zita , Márián Teréz , Garai Ildikó , Balkay László , Trencsényi György , Thuróczy Julianna
Published: December 2013

The relationship between metabolic disorders and the distribution of fat in different body regions is not clearly understood in humans. The aim of this study was to develop a suitable method for assessing the regional distribution of fat deposits and their metabolic effects in dogs. Twenty-five dogs were subjected to computed tomographic (CT) imaging and blood sampling in order to characterise their metabolic status. The different fat areas were measured on a cross-sectional scan, and the animals’ metabolic status was evaluated by measuring fasting glucose, insulin and leptin levels. The volume of visceral adipose tissue is the main determinant of leptin levels. The correlation of visceral fat volume and leptin concentration was found to be independent of insulin levels or the degree of insulin resistance. There was a positive correlation between the visceral to subcutaneous fat volume ratio and serum insulin concentration, and a similar trend was observed in the relationship of fat ratio and insulin resistance. The distribution of body fat essentially influences the metabolic parameters in dogs, but the effects of adiposity differ between humans and dogs. The findings can facilitate a possible extrapolation of results from animal studies to humans with regard to the metabolic consequences of different obesity types.
Laparoscopos appendectomia 2013-ban – hogyan vált egy megtűrt műtét gold standard beavatkozássá?
Authors: Besznyák István , Svastics Imre , Egyed Tamás , Szentpétery Félix , Teknős Dániel , Nagy Péter , Mersich Tamás , Dede Kristóf , Bursics Attila
Published: December 2013

Absztrakt

Bevezetés:A laparoscopos appendectomia egyike az elsőként kidolgozott minimálisan invazív sebészeti eljárásoknak, mégis a mai napig ellentmondásos a megítélése mind az előnyeit, mind az indikációit tekintve.Módszer:A szerzők áttekintik és elemzik a laparoscopos appendectomiával kapcsolatos irodalmat, valamint a 2005. január 1. és 2013. szeptember 30. között laparoscopos és nyílt technikával appendectomizált betegeik adatait.Eredmények:Az Uzsoki Kórház Sebészeti Osztályán 2005. január 1. és 2013. szeptember 30. között 1214 betegnél történt appendectomia appendicitis acuta miatt. 1065 (87,73%) betegnél laparoscoposan, 149 (12,27%) betegnél nyílt technikával végeztük a műtétet. 2006 januárja óta alapelvünk, hogy appendicitis esetén a laparoscopos appendectomia az elsőként választandó eljárás. Konverzióra a betegek 16,5%-ánál kényszerültünk, az osztály műtéti tapasztalatának növekedésével a konverziók aránya csökkenő tendenciát mutat.Következtetések:A laparoscopos appendectomia előnyei az elmúlt évtizedben egyértelművé váltak a nyílt műtéttel összehasonlítva, a beavatkozás minden korcsoportban ajánlható. Acut appendicitis gyanúja esetén osztályunkon elsőként választandó eljárás a laparoscopos műtét, amelynek eredményei legalább olyan jók, mint a nyílt appendectomiáéi. A laparoscopos appendectomia rutinszerű végzése kiváló alapot ad a haladó laparoscopos műtétek elsajátításához, az appendectomia nem veszíti el tanuló jellegét a laparoscopos megközelítés miatt.
Epekövekben levő baktériumok előfordulásának gyakorisága
Authors: Lévay Bernadett , Szabó Györgyi , Szijártó Attila , Gamal Eldin Mohamed
Published: December 2013

Absztrakt

Bevezetés: A hasüregben hagyott epekövek okozta septicus szövődmények jól ismertek az irodalomból. Hasüregi tályog, bélperforatio gyakran leírt szövődmény, de leírtak már epekövet sérvtömlőben is, sőt, hivatkozás történt egy betegre, aki expectorálta epekövét, amely a rekeszen át került be a légutakba néhány év alatt. A szövődmények megjelenése epeműtét után néhány héttől évekig tarthat. Anyagok és módszerek: A szerzők egymást követő 50 tervezett cholecystectomia (36 nő / 14 férfi, átlagéletkoruk: 60,8 ± 6,8 év) során minden hólyagból egy darab epekövet izoláltak, majd az ebből készített kőoldatot és epét mikrobiológiai vizsgálatra küldték, majd ezek eredményeit elemezték. Eredmények: A szerzők által kivett 50 darab epekőben 16 esetben fordult elő baktérium. Ebből 4 acut gyulladás jeleit mutató epehólyagból, 8 krónikusan gyulladt hólyagból, 4 epekő empyemás epehólyagból került vizsgálatra. Enterális kórokozó (Esherichia coli, Enterococcus faecalis, Enterobacter cloacae) 13 esetben, nem enterális (Klebsiella penumoniae, Streptococcus alfa-haemoliticus) 3 esetben volt jelen. Nőktől származó epehólyagban 12 esetben volt pozitív a tenyésztés, míg férfiaknál 4 esetben. Következtetések: Az epekövek egy részében baktériumok azonosíthatóak, amelyek felelősek lehetnek a későbbi gyulladásos szövődményekért.
Tuberous sclerosis complex diagnosed from oral lesions
Authors: Araujo Leonardo de Jesus , Muniz Guilherme Braga , Santos Edmilson , Ladeia Joao Paulo Versiani , Martelli Junior Hercilio , Bonan Paulo Rogerio Ferreti
Published: December 2013

CONTEXT: Tuberous sclerosis complex (TSC) is a genetic disease in the group known as neurocutaneous syndromes, with dominant autosomal inheritance. It is characterized by skin and adnexal lesions and central and peripheral nervous system tumors, with neurological and psychiatric findings. It may affect the heart, kidneys, eyes, face, bones, lungs, stomach and dentition. CASE REPORT: We present the case of a 66-year-old man with dermatological signs that included hypopigmented maculae, confetti-like lesions, shagreen plaque, angiofibromas on nasolabial folds, neck and back, nail dystrophy and periungual fibromas on fingers and toes. An electroencephalogram produced normal results, but magnetic resonance imaging showed a nodular image measuring 1.2 x 1.0 cm close to the Monro foramen, which was similar to cerebral parenchyma and compatible with a subependymal giant-cell astrocytoma. A conservative approach was taken, through control imaging examinations on the lesion for seven years, with absence of any expansive process or neurological symptoms. Abdominal ultrasonography revealed a solid, heterogenic and echogenic mass with a calcified focus, measuring 4.6 x 3.4 cm, in the rightkidney, compatible with angiomyolipoma. The patient was treated by means of complete nephrectomy because of malignant areas seen on histopathological examination and died one month after the procedure. This case report illustrates the importance of oral clinical findings such as dental enamel pits and angiofibromas in making an early diagnosis of TSC, with subsequent screening examinations, treatment and genetic counseling.
Renal artery pseudoaneurysm after blunt renal trauma: report on three cases and review of the literature
Authors: Yamacake Kleiton Gabriel Ribeiro , Lucon Marcos , Lucon Antonio Marmo , Mesquita Jose Luiz Borges , Srougi Miguel
Published: December 2013

CONTEXT: Renal artery pseudoaneurysm is a rare complication after renal injury but should be suspected whenever there is recurrent hematuria after renal trauma. CASE REPORTS: We present three cases of pseudoaneurysm after blunt renal trauma and a review of the literature. All patients underwent renal angiography. Two cases were diagnosed during the initial hospital stay due to hematuria, or in the follow-up period during recovery. One patient was hemodynamically unstable. Two patients successfully underwent coil embolization in a single session. In the other case, selective embolization was attempted, but was unsuccessful because artery catheterization was impossible. Procedural and medical success and complications were retrospectively assessed from the patients' records. The clinical presentation, treatment options and clinical decisions are discussed. CONCLUSIONS: Renal artery pseudoaneurysm may develop acutely or even years after the initial injury. Signs and symptoms may have a wide spectrum of presentation. Selective angiographic embolization is an effective treatment that reduces the extent of parenchymal infarction.
Desenvolvimento e Validação Factorial da Escala de Motivos face à Parentalidade
Authors: Matias Marisa , Fontaine Anne Marie
Published: December 2013

Ter filhos é uma decisão influenciada por vários fatores. O objetivo deste estudo foi descrever a construção e validação de um instrumento em língua portuguesa para análise dos motivos subjacentes à decisão de ter ou não ter filhos. A Escala de Motivos face à Parentalidade, construída com base numa revisão de estudos e escalas pré-existentes, foi administrada a duas amostras e alvo de análise fatorial exploratória e confirmatória. A escala final é composta por 30 itens divididos em quatro fatores: Enriquecimento Emocional, Reconhecimento Social, Interferência no Estilo de Vida e Antecipação de Problemas de desenvolvimento na criança. Todas as subescalas apresentaram bons índices de consistência interna e boa estabilidade fatorial. Considera-se que a escala aqui apresentada poderá contribuir para uma melhor compreensão da temática da decisão de ter ou não filhos.
Distúrbio Específico de Linguagem: Caracterização Neuropsicológica
Authors: Coelho Sandra , Albuquerque Cristina Petrucci , Simões Mário Rodrigues
Published: December 2013

O presente estudo pretende caracterizar o funcionamento neuropsicológico de crianças com Distúrbio Específico de Linguagem (DEL) nas áreas da memória visual e verbal, atenção/funções executivas e funções visuopercetivas. A amostra é constituída por 28 crianças com DEL e 28 crianças sem DEL, sendo ambos os grupos equiparáveis em termos de idade, género, ano de escolaridade e nível socioeconómico. Para o efeito, recorreu-se a testes da Bateria de Avaliação Neuropsicológica de Coimbra e os dados foram analisados através de testes estatísticos paramétricos e não paramétricos. De um modo geral, os resultados obtidos diferenciam os desempenhos das crianças com DEL dos observados em crianças sem DEL. Em concreto, e comparativamente ao grupo de controlo, o grupo de crianças com DEL apresentou resultados significativamente inferiores na memória visual e memória verbal, na atenção seletiva e sustentada, nas funções executivas, na fluência verbal semântica, nas funções visuopercetivas e na velocidade de processamento.