bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract SY11-03: Mechanisms of ATM activation
Authors: Paull Tanya T. , Lee Ji-Hoon , Ditch Scott , Guo Zhi
Published: August 2012

The Ataxia-Telangiectasia Mutated (ATM) kinase initiates a rapid cascade of protein phosphorylation in response to double-strand breaks in chromosomal DNA. The critical targets of ATM during this response include many tumor suppressors involved in cell cycle progression and apoptosis. The DNA damage response is thus defective in cells lacking ATM; however, there are also many indications that cells lacking ATM are defective in responses to other forms of stress, particularly oxidative stress. Mammalian cells lacking ATM exhibit high levels of reactive oxygen species and indications of chronic oxidative stress. In addition, the shortened lifespan, haematopoietic stem cell loss, and increased lymphomagenesis seen in A-T mouse models can be suppressed by antioxidants, suggesting that oxidative stress constitutes an important part of the A-T phenotype and is important for cancer progression. We have observed robust ATM activation in human cell lines in response to oxidative stress, in the absence of apparent DNA damage. In addition, oxidation of purified recombinant ATM in vitro induces ATM activation in the absence of DNA DSBs and the MRN complex. The oxidized form of ATM is a disulfide-crosslinked dimer containing several disulfide bonds. Mutation of a critical cysteine residue involved in disulfide bond formation specifically blocks activation via the oxidation pathway, both in vitro with purified components and in human cells. Identification of this pathway explains many observations of ATM activation under conditions of oxidative stress, and shows that ATM is an important sensor of reactive oxygen species (ROS) in vivo. Here we investigate how the oxidation pathway of ATM activation is affected by small molecules, specifically by resveratrol and related compounds, and how this affects cell cycle checkpoint responses in human cells. We also show in vitro that ATM is a direct target of these compounds and investigate the mechanism underlying the effects on ATM function.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY11-03. doi:1538-7445.AM2012-SY11-03
Abstract SY14-01: Investigating MTORC1 inhibition downstream of Apc loss in vivo
Authors: Sansom Owen J.
Published: August 2012

The Apc tumour suppressor gene is mutated in up to 80% percent of colorectal cancers (CRC), therefore strategies specifically targeting Apc deficient cells in vivo may be of therapeutic relevance. Thus far most work in murine models have focussed on models of adenomas where only Apc is lacking (and not other mutations that drive progression). In my talk, I will discuss our recent work inhibiting mTOR in Apc deficient cells in vivo either via small molecules or genetically deleting critical components of mTORC1 (Raptor) and mTORC2 (Rictor).

Here we show that Apc deficient cells are dependent on mTORC1 for proliferation (in a S6 kinase dependent manner). However additional mutation of KRAS or p53 renders the cells insensitive to mTORC1 inhibition. I will discuss the mechanisms underpinning this resistance and how overcoming these may allow us to target more advanced intestinal tumours in vivo.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY14-01. doi:1538-7445.AM2012-SY14-01
Abstract SY21-01: Chromatin remodeling proteins in transcription and development
Authors: Archer Trevor K. , Trotter Kevin W. , Singh Ajeet
Published: August 2012

The assembly of DNA with histones into chromatin provides a mechanism to regulate gene expression in time and space. The precise architecture of various DNA regulatory elements within the hierarchy of chromatin structures controls the access and activity of transacting factors, both protein and RNA. Epigenetic marks within DNA and histones allow regulatory information to act during development and across generations. The enzymes that mediate these processes are diverse and multifunctional, capable of posttranslationally modifying DNA and histones as well as remodeling the chromatin architecture. Among these enzymes the human SWI/SNF or BRG1 remodeling complex is particularly important with clear roles in signal transduction, development and cancer. In the presentation I will describe our recent work on the detailed mechanism of action of the BRG1 complex in gene expression and during early development in the mouse. We focus on the contribution that sub-domains in the BRG1 N terminus makes if protein partners outside the normal BRG1 associated Factors (BAFs) to initiate steroid receptor mediated transcription. Studies of the complex during development highlight the roles of individual BAF proteins and their contribution to organogenesis. These findings highlight the intimate connections between chromatin remodeling and epigenetics for normal healthy development.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY21-01. doi:1538-7445.AM2012-SY21-01
Endobronchial Valves for Persistent Postoperative Pulmonary Air Leak: Accurate Monitoring and Functional Implications
Authors: Dooms Christophe A. , De Leyn Paul R. , Yserbyt Jonas , Decaluwe Herbert , Ninane Vincent
Published: August 2012

An alveolar-pleural fistula is a communication between the pulmonary parenchyma distal to a segmental bronchus and the pleural space. A postoperative pulmonary expiratory air leak after an anatomic pulmonary resection is usually managed conservatively. The use of endobronchial valves is a minimal invasive method that may be effective for the treatment of a persistent postoperative pulmonary air leak. We present and discuss the advantages of a digital thoracic drainage system for the accurate, objective and reproducible air leak assessment during endobronchial valve placement. Our case also illustrates that, even after lobectomy, lobar exclusion with valves allows air leak resolution without atelectasis and with moderate functional alteration. We discuss the anatomic and physiologic changes induced by valves placed for air leak closure.
Impact of Laryngeal Findings on Acoustic Parameters of Patients with Laryngopharyngeal Reflux
Authors: Akyildiz Serdar , Ogut Fatih , Varis Ahmet , Kirazli Tayfun , Bor Serhat
Published: August 2012

Objectives: To identify the effects of laryngopharyngeal reflux (LPR)-related laryngeal findings on objective voice parameters. Methods: Two hundred and thirty patients clinically diagnosed as having LPR and 48 healthy controls were included. The reflux finding score was determined for each subject via videolaryngoscopy. The acoustic parameters evaluated were jitter, shimmer, noise-to-harmonic ratio and Voice Turbulence Index (VTI). Results: Shimmer and VTI showed statistically significant differences between the LPR and control groups among males (p < 0.05). For females, all of the 4 acoustic voice parameters were significantly different between the two groups (p < 0.05). Erythema/hyperemia was found to affect the highest number of voice parameters. VTI was found to be affected by the highest number of laryngeal findings. Conclusion: Objective voice changes were documented in LPR patients, with VTI being the most affected parameter, and therefore it should be considered in the acoustic analysis of patients with LPR in addition to the conventional parameters. With hyperemia in the first rank, ventricular obliteration, pseudosulcus and vocal fold edema are found to have an impact on voice, suggesting that these should be concentrated on in the diagnosis and follow-up of LPR patients with voice disorders.
Hemophagocytic Syndrome in the Course of Sudden Sensorineural Hearing Loss
Authors: Tamura Atsushi , Matsunobu Takeshi , Kurita Akihiro , Shiotani Akihiro
Published: August 2012

Objective: This paper aims to comprehensively document a rare case of sensorineural hearing loss accompanied by hemophagocytic syndrome which could be one of the causes of cochlear dysfunction. Methods: A 63-year-old man presented with right-sided sudden hearing loss and dizziness and pure-tone audiometry showed a right-sided sensorineural hearing loss. The patient was treated with steroid pulse infusion therapy, ATP and vitamin B12. Results: Bone marrow specimen revealed hemophagocytic cells and the diagnosis of hemophagocytic syndrome was made. A blood culture grew Capnocytophaga. The prognosis for hearing recovery was poor. Conclusion: Although viral infection and cochlear circulatory dysfunction have been suggested to be associated with sudden sensorineural hearing loss, hemophagocytic syndrome due to bacterial infection which produces high cytokine levels might cause dysfunction of the inner ear.
Evaluation of the mRECIST and α-Fetoprotein Ratio for Stratification of the Prognosis of Advanced-Hepatocellular-Carcinoma Patients Treated with Sorafenib
Authors: Kawaoka Tomokazu , Aikata Hiroshi , Murakami Eisuke , Nakahara Takashi , Naeshiro Noriaki , Tanaka Mio , Honda Yoji , Miyaki Daisuke , Nagaoki Yuko , Takaki Shintaro , Hiramatsu Akira , Waki Koji , Takahashi Shoichi , Chayama Kazuaki
Published: August 2012

Objective: To compare the assessment of response and prognosis of patients to sorafenib treatment by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP). Methods: Sixty-six patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib were enrolled in this retrospective study. The response to treatment was evaluated by RECIST, mRECIST and changes in AFP and DCP. Results: The median survival time of all patients was 8.6 months. The median time to radiological progression was 3.3 months. The response rates [complete response (CR) + partial response (PR)] by RECIST and mRECIST were 3.0 and 9.0%, respectively, while the disease control rates [CR + PR + stable disease (SD)] were 50 and 50%, respectively. Assessment by mRECIST of overall survival provided a better stratification of the patients according to the response to treatment (p = 0.009) than RECIST (p = 0.09). Assessment of overall survival by a change in AFP ratio of ≤1 at 8 weeks was better than that of >1 at 8 weeks (p = 0.002). The DCP ratio was not useful for assessment of overall survival. Multivariate analysis identified mRECIST response (CR + PR + SD; p = 0.001), AFP ratio at 8 weeks (≤1; p = 0.046) and Child-Pugh A before treatment (p = 0.012) as significant and independent determinants of survival. The combination of AFP ratio at 8 weeks, assessment by mRECIST and Child-Pugh score before treatment allows stratification of prognosis of patients treated with sorafenib. Conclusion: The combination of mRECIST and AFP ratio is useful for the assessment of prognosis of patients with advanced HCC treated with sorafenib.
The PxDLLCxE Sequence in Conserved Region 2 of Human Papilloma Virus 18 Protein E7 Is Required for E7 Binding to Centromere Protein C
Authors: Yaginuma Yuji , Eguchi Ayami , Yoshimoto Masafumi , Ogawa Katsuhiro
Published: August 2012

High-risk human papillomaviruses (HPVs) are etiologically linked to human cervical and oral cancers. HPV infection leads to aneuploidy, a numerical chromosomal aberration caused by dysregulation of chromosomal segregation. We found that high-risk HPV18 and HPV58 E7 proteins bind to centromere protein C (CENP-C), a component of the kinetochore that is essential for proper chromosomal segregation. Low-risk HPV4, HPV6, and HPV11 E7s do not bind to CENP-C. The PxDLLCxE sequence in conserved region 2 (CR2) of HPV18 E7 is required for E7 binding to CENP-C. Our results indicate that differences in the ability of high- and low-risk HPV E7s to bind to CENP-C reflect the different oncogenic potentials of high- and low-risk type HPVs.
The Deuteronomistic Heritage in the Psalms
Authors: Marttila Marko
Published: August 2012

The Deuteronomistic school/movement has left its traces in several biblical books. The Deuteronomistic History from Deuteronomy to Second Kings is not the only representative of Deuteronomistic (Dtr) theology—Dtr phraseology also occurs repeatedly in the book of Psalms. The most significant examples are Psalms 18, 25, 44, 50, 74, 78, 79, 81, 89 and 132. The Dtr influence originated differently in these psalms. In some cases editors inserted passages with Dtr colour into an earlier prayer, but in some other cases the original author of the psalm had employed Dtr language. It seems likely that Deuteronomism represented a kind of normative theology in the Second Temple period. However, this heritage was open for reinterpretation. Psalm 44, at least, protests against the Dtr way of thinking.
Emotional Reactions Toward School Situations
Authors: Lipnevich Anastasiya A. , MacCann Carolyn , Bertling Jonas P. , Naemi Bobby , Roberts Richard D.
Published: August 2012

The current study investigated self-reported positive affect (PA) and negative affect (NA) in high school students ( N = 451) within three academic contexts: homework, classwork/tests, and after-school activities. We examined whether context-specific emotions predicted grades, life satisfaction, and discipline records. Our findings revealed that context may be important when examining test-criterion relations, with students’ affective reactions during extracurricular activities leading to different relationships with outcomes than reported affect during homework and classwork/testing. Furthermore, we found that PA predicted student grades and satisfaction with life to a much greater extent than NA. Practical implications and future directions are discussed.
Trait Emotional Intelligence and University Graduation Outcomes
Authors: Keefer Kateryna V. , Parker James D.A. , Wood Laura M.
Published: August 2012

This study explored the utility of trait emotional intelligence (EI) for predicting students’ university graduation outcomes six years after enrolment in university. At the start of the program, 1,015 newly registered students completed a brief multidimensional self-report EI assessment and provided consent to track their subsequent degree progress via official university records. Using latent profile analysis (LPA), participants were sorted into five classes that differed in the overall EI level and in the relative strengths and weaknesses on individual EI dimensions. Greater likelihood of degree noncompletion at the 6-year follow-up was uniquely associated with having a low-EI profile with particularly pronounced weaknesses in the interpersonal and stress management domains, after controlling for high school grades and gender. Comparative levels of predictive utility could not be achieved by examining scores on each EI dimension independently. Authors discuss practical advantages of LPA over traditional variable-centered approaches for identifying and assisting students at risk for degree noncompletion.
Alcohol Availability and Neighborhood Poverty and Their Relationship to Binge Drinking and Related Problems Among Drinkers in Committed Relationships
Authors: McKinney Christy M. , Chartier Karen G. , Caetano Raul , Harris T. Robert
Published: August 2012

The authors examined the relationship of alcohol outlet density (AOD) and neighborhood poverty with binge drinking and alcohol-related problems among drinkers in married and cohabitating relationships and assessed whether these associations differed across sex. A U.S. national population couples survey was linked to U.S. Census data on AOD and neighborhood poverty. The 1,784 current drinkers in the survey reported on their binge drinking, alcohol-related problems, and other covariates. AOD was defined as the number of alcohol outlets per 10,000 persons and was obtained at the zip code level. Neighborhood poverty was defined as having a low (<20%) or high (≥20%) proportion of residents living in poverty at the census tract level. We used logistic regression for survey data to estimate odds ratios and 95% confidence intervals and tested for differences of associations by sex. Associations of neighborhood poverty with binge drinking were stronger for male than for female drinkers. The association of neighborhood poverty with alcohol-related problems was also stronger for men than for women. We observed no relationships between AOD and binge drinking or alcohol-related problems in this couples survey. Efforts to reduce binge drinking or alcohol-related problems among partners in committed relationships may have the greatest impact if targeted to male drinkers living in high-poverty neighborhoods. Binge drinking and alcohol-related problems, as well as residence in an impoverished neighborhood are risk factors for intimate partner violence (IPV) and other relationship conflicts.
English pauper lunatics in the era of the old poor law
Authors: Miller Edgar
Published: August 2012

Many of those considered to be insane in the past were regarded as paupers and so came within the ambit of the poor law. Little work has yet been published on the ways in which the poor law dealt with the psychologically disturbed during the era of the old poor law ( c.1601–1834). The present paper outlines the old poor law which said very little about madness as a specific problem, with the general implication that they were to be dealt with in the same way as others considered to be in need of relief. It appears that this was generally the case with the exception that the insane were sometimes sent to asylums. They were also liable to be treated as vagrants. Some limitations and problems with primary sources are also noted.
Automatism, Surrealism and the making of French psychopathology: the case of Pierre Janet
Authors: Bacopoulos-Viau Alexandra
Published: August 2012

This article deals with the clinical use of ‘automatic writing’ by the French psychologist Pierre Janet at the fin de siècle and its later appropriation by Surrealist poets during the inter-war period. Of special interest are the acknowledged influences of Surrealism’s leading representative. Why did André Breton, in his mythical love affair with Freudianism, systematically silence his indebtedness to the Janetian model of the mind? In order to examine this question we turn to a little-studied theme: Janet’s increasing distance from Spiritism and psychical research. In seeking to establish his new discipline within a medical framework, Janet erected barriers between the psychological sciences and such seemingly ‘extra-scientific’ fields. In so doing, he placed himself at odds with other members of the intellectual community who saw in the automatic manifestations of the mind a source of exalted creativity.
Early Season NFL Over/Under Bias
Authors: DiFilippo Michael , Krieger Kevin , Davis Justin , Fodor Andy
Published: August 2012

Popular wisdom regarding athletics is that offenses are at a relative disadvantage in the early portion of seasons. The authors present evidence that this anecdotal belief holds true over the 2000-2010 National Football League (NFL) seasons. This is reflected in lower offensive yardage, fewer first downs, and fewer points scored. While total points scored are significantly lower in Week 1 of NFL seasons, bookmakers fail to reduce the total lines posted on these games. The authors find a strategy betting under total lines of all Week 1 games over the 2000-2010 NFL seasons yields a statistically significant return of 13.6% per game.
Protective effects of indomethacin and dexamethasone in a goat model with intrauterine balloon aortic valvuloplasty
Authors: Zhou Kaiyu , Wu Gang , Li Yifei , Zhao Liang , Zhou Rong , Zhu Qi , Huang Xupei , Mu Dezhi , Hua Yimin
Published: August 2012

Background

Intrauterine balloon aortic valvuloplasty (IUBAV) has been used for critical aortic stenosis. However, it is necessary to determine the fetal impairments such as preterm birth after this approach and to find a way to prevent or reduce them.

Methods

In the present study, we evaluated the therapeutic value of indomethacin (IDM) and dexamethasone (DXS) on reducing the preterm birth rate in experimental goats after IUBAV.

Results

Our results indicated that the administration of IDM/DXS significantly reduced the rate of premature birth. IDM/DXS treatment led to preservation of myocardial ultrastructure with less damage, and amelioration of the fetal and placental circulation. Furthermore, we found that norepinephrine (NE) level was positively associated with the degree of myocardial damage. IDM/DXS administration led to a significant decrease of operation-induced increase of NE levels, which may be associated with the protective effects of IDM/DXS. Lastly, we found that the administration of IDM/DXS did not induce the risk of ductus arteriosus closure or slow down fetal growth.

Conclusions

Our results indicate that IDM/DXS promotes a better gestational outcome at least partially by reducing stress response during and after the operation of IUBAV in the goat model. IDM/DXS may be a useful application in human patients during IUBAV intervention.
Cloudgene: A graphical execution platform for MapReduce programs on private and public clouds
Authors: Schönherr Sebastian , Forer Lukas , Weißensteiner Hansi , Kronenberg Florian , Specht Günther , Kloss-Brandstätter Anita
Published: August 2012

Background

The MapReduce framework enables a scalable processing and analyzing of large datasets by distributing the computational load on connected computer nodes, referred to as a cluster. In Bioinformatics, MapReduce has already been adopted to various case scenarios such as mapping next generation sequencing data to a reference genome, finding SNPs from short read data or matching strings in genotype files. Nevertheless, tasks like installing and maintaining MapReduce on a cluster system, importing data into its distributed file system or executing MapReduce programs require advanced knowledge in computer science and could thus prevent scientists from usage of currently available and useful software solutions.

Results

Here we present Cloudgene, a freely available platform to improve the usability of MapReduce programs in Bioinformatics by providing a graphical user interface for the execution, the import and export of data and the reproducibility of workflows on in-house (private clouds) and rented clusters (public clouds). The aim of Cloudgene is to build a standardized graphical execution environment for currently available and future MapReduce programs, which can all be integrated by using its plug-in interface. Since Cloudgene can be executed on private clusters, sensitive datasets can be kept in house at all time and data transfer times are therefore minimized.

Conclusions

Our results show that MapReduce programs can be integrated into Cloudgene with little effort and without adding any computational overhead to existing programs. This platform gives developers the opportunity to focus on the actual implementation task and provides scientists a platform with the aim to hide the complexity of MapReduce. In addition to MapReduce programs, Cloudgene can also be used to launch predefined systems (e.g. Cloud BioLinux, RStudio) in public clouds. Currently, five different bioinformatic programs using MapReduce and two systems are integrated and have been successfully deployed. Cloudgene is freely available athttp://cloudgene.uibk.ac.at.
L1 cell adhesion molecule overexpression in hepatocellular carcinoma associates with advanced tumor progression and poor patient survival
Authors: Guo Xiaodong , Xiong Lu , Zou Lin , Sun Ting , Zhang Jing , Li Hanwei , Peng Ruiyun , Zhao Jingmin
Published: August 2012

Objective

L1 cell adhesion molecule (L1CAM), as a member of the immunoglobulin superfamily, has recently been observed in a variety of human malignancies. However, no data of L1CAM are available for hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of L1CAM in HCC and determine its correlation with tumor progression and prognosis.

Methods

One-hundred and thirty HCC patients who had undergone curative liver resection were selected and immunohistochemistry, Western blotting, and quantitative real time polymerase chain reaction (Q-PCR) were performed to analyze L1CAM expression in the respective tumors.

Results

Immunohistochemistry, Western blotting, and Q-PCR consistently confirmed the overexpression of L1CAM in HCC tissues compared with their adjacent nonneoplastic tissues at both protein and gene level (both P <0.01). Additionally, the high expression of L1CAM was significantly associated with advanced tumor stage (P = 0.02) and advanced tumor grade (P = 0.03), respectively. Moreover, HCC patients with high L1CAM expression were significantly associated with lower 5-year overall survival (P <0.01) and lower 5-year disease-free survival (P <0.01), respectively. The Cox proportional hazards model further showed that L1CAM over-expression was an independent poor prognostic factor for both 5-year disease-free survival (P = 0.02) and 5-year overall survival (P = 0.008) in HCC.

Conclusion

Our data suggest for the first time that L1CAM expression in HCC was significantly correlated with the advanced tumor progression and was an independent poor prognostic factor for both overall survival and disease-free survival in patients with HCC.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1970024872761542
Probing the role of stochasticity in a model of the embryonic stem cell – heterogeneous gene expression and reprogramming efficiency
Authors: Chickarmane Vijay , Olariu Victor , Peterson Carsten
Published: August 2012

Background

Embryonic stem cells (ESC) have the capacity to self-renew and remain pluripotent, while continuously providing a source of a variety of differentiated cell types. Understanding what governs these properties at the molecular level is crucial for stem cell biology and its application to regenerative medicine. Of particular relevance is to elucidate those molecular interactions which govern the reprogramming of somatic cells into ESC. A computational approach can be used as a framework to explore the dynamics of a simplified network of the ESC with the aim to understand how stem cells differentiate and also how they can be reprogrammed from somatic cells.

Results

We propose a computational model of the embryonic stem cell network, in which a core set of transcription factors (TFs) interact with each other and are induced by external factors. A stochastic treatment of the network dynamics suggests that NANOG heterogeneity is the deciding factor for the stem cell fate. In particular, our results show that the decision of staying in the ground state or commitment to a differentiated state is fundamentally stochastic, and can be modulated by the addition of external factors (2i/3i media), which have the effect of reducing fluctuations in NANOG expression. Our model also hosts reprogramming of a committed cell into an ESC by over-expressing OCT4. In this context, we recapitulate the important experimental result that reprogramming efficiency peaks when OCT4 is over-expressed within a specific range of values.

Conclusions

We have demonstrated how a stochastic computational model based upon a simplified network of TFs in ESCs can elucidate several key observed dynamical features. It accounts for (i) the observed heterogeneity of key regulators, (ii) characterizes the ESC under certain external stimuli conditions and (iii) describes the occurrence of transitions from the ESC to the differentiated state. Furthermore, the model (iv) provides a framework for reprogramming from somatic cells and conveys an understanding of reprogramming efficiency as a function of OCT4 over-expression.
Updates on HIPK2: a resourceful oncosuppressor for clearing cancer
Authors: D’Orazi Gabriella , Rinaldo Cinzia , Soddu Silvia
Published: August 2012

Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented protein that exploits its kinase activity to modulate key molecular pathways in cancer to restrain tumor growth and induce response to therapies. HIPK2 phosphorylates oncosuppressor p53 for apoptotic activation. In addition, also p53-independent apoptotic pathways are regulated by HIPK2 and can be exploited for anticancer purpose too. Therefore, HIPK2 activity is considered a central switch in targeting tumor cells toward apoptosis upon genotoxic damage and the preservation and/or restoration of HIPK2 function is crucial for an efficient tumor response to therapies. As a proof of principle, HIPK2 knockdown impairs p53 function, induces chemoresistance, angiogenesis, and tumor growth in vivo, on the contrary, HIPK2 overexpression activates apoptotic pathways, counteracts hypoxia, inhibits angiogenesis, and induces chemosensitivity both in p53-dependent and -independent ways. The role of HIPK2 in restraining tumor development was also confirmed by studies with HIPK2 knockout mice. Recent findings demonstrated that HIPK2 inhibitions do exist in tumors and depend by several mechanisms including HIPK2 cytoplasmic localization, protein degradation, and loss of heterozygosity (LOH), recapitulating the biological outcome obtained by RNA interference studies in tumor cells, such as p53 inactivation, resistance to therapies, apoptosis inhibition, and tumor progression. These findings may lead to new diagnostic and therapeutic approaches for treating cancer patients. This review will focus on the last updates about HIPK2 contribution in tumorigenesis and cancer treatment.
Response of hemorrhagic bullous skin lesions of the breast secondary to primary systemic amyloidosis to a five-drug combination chemotherapy: a case report and review of the literature
Authors: Agheli Aref , Becker Marvin , Becker Gary , Chaudhry M Rashid , Wang Jen C
Published: August 2012

Two major types of amyloidosis are primary amyloidosis or amyloid light chain amyloidosis and secondary amyloidosis. Although amyloidosis involves a variety of organ systems including skin, the occurrence of bullous skin lesions is rare. Little is known about the mechanism of blister formation. These blisters are often hemorrhagic and typically occur in the oral mucosa. Only a few case reports have described skin involvement in systemic amyloidosis. The manifestation of bullous lesions on the breast in association with primary amyloidosis has not been previously reported. Therefore, we report a case of cutaneous hemorrhagic bullous of the breast secondary to primary systemic amyloidosis, which may be important for medical oncologists to be aware of this uncommon presentation of plasma cell dysrasias. Furthermore, this case only partially responded to the commonly used multiple myeloma-type regimen, the skin lesions responded completely to a five-drug combination chemotherapy regimen, utilizing immunomodulators, liposomal doxorubicin, cyclophosphamide, bortezomib, and dexamethasone, suggesting that a more aggressive modality of chemotherapy may be necessary to treat such cases.
Interleukin-6 is the strongest predictor of 30-day mortality in patients with cardiogenic shock due to myocardial infarction
Authors: Andrié René P , Becher Ulrich M , Frommold Ricarda , Tiyerili Vedat , Schrickel Jan W , Nickenig Georg , Schwab Jörg O
Published: August 2012

Introduction

Cardiogenic shock (CS) remains the leading cause of death in patients hospitalized for myocardial infarction (MI). Systemic inflammation with inappropriate vasodilatation is observed in many patients with CS and may contribute to an excess mortality rate. The purpose of this study was to determine the predictive role of serial measurements of Nt-proBNP, interleukin-6 (IL-6), and procalcitonin (PCT) for 30-day mortality in patients with CS due to MI.

Methods

The present study is a prospective single-center study including 87 patients with MI complicated by CS treated with acute revascularization and intraaortic balloon counterpulsation (IABP) support. Predictive values of plasma levels at admission (T0), after 24 hours (T1), and after 72 hours (T2) were examined according to 30-day mortality.

Results

Significant differences between survivors (n = 59) and nonsurvivors (n = 28) were seen for Nt-proBNP at T0, for IL-6 at T0 and T1, and for PCT at T1 and T2. According to ROC analyses, the highest accuracy predicting 30-day mortality was seen at T0 for IL-6, at T1 for PCT, and at T2 for PCT. In univariate analysis, significant values were found for Nt-proBNP at T1, and for IL-6 and PCT at all points in time. Within the multivariate analysis, age, creatinine, and IL-6 were significant determinants of 30-day mortality, in which IL-6 showed the highest level of significance.

Conclusions

In patients with MI complicated by CS, IL-6 represented a reliable independent early prognostic marker of 30-day mortality. PCT revealed a significant value at later points in time, whereas Nt-proBNP seemed to be of lower relevance.
Mild metabolic acidosis impairs the β-adrenergic response in isolated human failing myocardium
Authors: Schotola Hanna , Toischer Karl , Popov Aron F , Renner André , Schmitto Jan D , Gummert Jan , Quintel Michael , Bauer Martin , Maier Lars S , Sossalla Samuel
Published: August 2012

Introduction

Pronounced extracellular acidosis reduces both cardiac contractility and the β-adrenergic response. In the past, this was shown in some studies using animal models. However, few data exist regarding how the human end-stage failing myocardium, in which compensatory mechanisms are exhausted, reacts to acute mild metabolic acidosis. The aim of this study was to investigate the effect of mild metabolic acidosis on contractility and the β-adrenergic response of isolated trabeculae from human end-stage failing hearts.

Methods

Intact isometrically twitching trabeculae isolated from patients with end-stage heart failure were exposed to mild metabolic acidosis (pH 7.20). Trabeculae were stimulated at increasing frequencies and finally exposed to increasing concentrations of isoproterenol (0 to 1 × 10-6M).

Results

A mild metabolic acidosis caused a depression in twitch-force amplitude of 26% (12.1 ± 1.9 to 9.0 ± 1.5 mN/mm2; n = 12; P < 0.01) as compared with pH 7.40. Force-frequency relation measurements yielded no further significant differences of twitch force. At the maximal isoproterenol concentration, the force amplitude was comparable in each of the two groups (pH 7.40 versus pH 7.20). However, the half-maximal effective concentration (EC50) was significantly increased in the acidosis group, with an EC50 of 5.834 × 10-8M (confidence interval (CI), 3.48 × 10-8 to 9.779 × 10-8; n = 9), compared with the control group, which had an EC50 of 1.056 × 10-8M (CI, 2.626 × 10-9 to 4.243 × 10-8; n = 10; P < 0.05), indicating an impaired β-adrenergic force response.

Conclusions

Our data show that mild metabolic acidosis reduces cardiac contractility and significantly impairs the β-adrenergic force response in human failing myocardium. Thus, our results could contribute to the still-controversial discussion about the therapy regimen of acidosis in patients with critical heart failure.
Clashing worldviews: Sources of disappointment in rural hospitality and tourism development
Authors: Chalip Laurence , Costa Carla A.
Published: August 2012

Hospitality and tourism have been advocated as tools for rural development, but they have often failed to achieve what was expected. Some failures may be due to the clash between development planners' worldviews and those of rural residents. This effect is demonstrated in a five-year
study of a community in Portugal. Planners focus on economic growth, seek returns from enlarged tourism scope, expect benefits to trickle down, and see hospitality and tourism development in its national and regional context. Consequently, they push policies even in the absence of local support,
favour return migrants as partners and are frustrated when local support is not forthcoming. Locals are skeptical about the growth enabled by hospitality and tourism, and fear that growth could threaten social equity. Consequently, they may distrust planners, feel the need to criticize hospitality
and tourism plans, act in ways that thwart those plans and fail to capitalize on opportunities. The resulting clash deflects hospitality and tourism development from reaching its goals. Community-based planning and applied ethnography could help planners circumvent the clash in worldviews,
and implement rural hospitality and tourism projects more effectively.
Hard labour at 35,000 feet: A reconsideration of emotional demands in airline service work
Authors: Sheehan Conor
Published: August 2012

This study offers a contemporary perspective on the factors affecting the emotional self-management of airline service agents within an increasingly challenging work environment. The methodological approach combined a review of the contemporary literature on 'emotion' work with exploratory
primary research involving longitudinal focus groups and 'life history' interviews (Ladkin 2004) with purposively selected respondents. The findings suggested that intensifying job demands and deteriorating working conditions continue to increase the alienating psychological costs of performing
emotional labour for air cabin crew. These costs appear greater where 'emotional reciprocity' is absent and emotional dissonance is evident. Some crew, however, continue to make emotional effort autonomously and spontaneously, and these incidences appear linked to personality trait characteristics
and positive service orientation. This work offers a rounded contextualization of respondents' life experiences with their emotional self-management challenges at work. Future research could further explore the 'reciprocity dynamic' as an enabler of service agents' emotional self-management.
Multiscale Modeling of Irradiation Induced Hardening in Iron Alloys
Authors: Mastorakos Ioannis N. , Zbib Hussein M. , Li Dongsheng , Khaleel Mohamed A. , Sun Xin
Published: August 2012

Structural materials in the new Generation IV reactors will operate in harsh radiation conditions coupled with high levels of hydrogen and helium production and will experience severe degradation of mechanical properties. Therefore, understanding of the physical mechanisms responsible for the microstructural evolution and corresponding mechanical property changes is critical. As the involved phenomena are very complex and span in several length scales, a multiscale approach is necessary in order to fully understand the degradation of materials in irradiated environments. In previous work, we used molecular dynamics simulations to develop critical rules for the mobility of dislocations in various iron alloys and their interaction with several types of defects that include, among others, helium bubbles and grain boundaries. In this work, Dislocation Dynamics simulations of iron alloys are used to study the mechanical behavior and the degradation under irradiation of large systems with high dislocation and defect densities.
Desafios e vantagens da utilização de critérios probabilísticos no planejamento de sistemas elétricos
Authors: Lima João Marcos , Lourenço Elizete Maria , Schilling Marcus Theodor
Published: August 2012

O sistema elétrico brasileiro tem sido projetado e operado através do uso de um conjunto de critérios de confiabilidade determinísticos. Esses critérios têm cumprido um papel importante no desenho e na operação do sistema durante décadas. Entretanto, tendem à utilização menos otimizada dos recursos disponíveis e no excesso de instalações de reserva de capacidade de transmissão, com impacto direto nos custos associados ao planejamento e operação do sistema. No planejamento da expansão, por exemplo, o critério determinístico mais utilizado é o n-1. Com relação à aprovação de intervenções programadas na rede básica, o principal critério determinístico adotado pelo Operador Nacional do Sistema Elétrico (ONS) é o n-2. Esse critério estabelece que o sistema elétrico deve suportar a indisponibilidade simultânea de um elemento de transmissão que esteja fora de operação para manutenção e de qualquer outro elemento por contingência, sem que ocorram violações dos indicadores de desempenho do sistema. Este artigo discute as limitações desses critérios determinísticos e propõe uma nova metodologia para avaliação de intervenções programadas, com base em técnicas probabilísticas. A nova metodologia permite uma avaliação mais precisa e flexível de agendamento de interrupções durante dias úteis em período de carga média, sem que o grau de risco do sistema se eleve a níveis preocupantes. Os resultados esperados com esse novo critério correspondem à redução dos custos de operação e de manutenção que, por sua vez, implicam na redução das tarifas de energia paga pelos consumidores.
Circulação extracorpórea e complicações no período pós-operatório imediato de cirurgias cardíacas
Authors: Torrati Fernanda Gaspar , Dantas Rosana Ap. Spadoti
Published: August 2012

OBJETIVO: Comparar a frequência de complicações apresentadas pelos pacientes, durante o pós-operatório imediato (POI), de cirurgias cardíacas de acordo com o tempo de circulação extra-corpórea (CEC). MÉTODOS: Estudo de natureza quantitativa, descritivo e correlacional com 83 pacientes adultos divididos em dois grupos de acordo com o tempo de CEC. RESULTADOS: Do total de pacientes, 44 (53%) tiveram o tempo de duração da CEC de até 85 minutos e 39 (47 %) tiveram o tempo acima de 85 minutos. As complicações foram comuns para ambos os grupos, sendo as mais frequentes dor e oligúria. No entanto, hemotórax, pneumotórax e infarto agudo do miocárdio ocorreram apenas no grupo com maior tempo de CEC. CONCLUSÃO: A maioria das complicações ocorridas no POI apresentou frequencia semelhante para os pacientes, independente do tempo de CEC.
Techniques of digital image analysis for histological quantification of melanin
Authors: Miot Hélio Amante , Brianezi Gabrielli , Tamega Andréia de Almeida , Miot Luciane Donida Bartoli
Published: August 2012

Morphometric analysis of tissue melanin may quantitatively contribute to research on pigmentation disorders. The authors present three methods for image analysis, which allow for identification of melanin-equivalent pixels in the epidermis using Fontana-Masson stain and, therefore, for the calculation of its percentage in the different epidermal layers. Moreover, they discuss the main elements related to the analysis and the need for rigorous standardization of the process.
Lipschütz ulcer (ulcus vulvae acutum): a rare cause of genital lesion
Authors: Brinca Ana , Canelas Maria Miguel , Carvalho Maria João , Vieira Ricardo , Figueiredo Américo
Published: August 2012

Lipschütz Ulcer, or ulcus vulvae acutum, is a rare and probably underdiagnosed entity that usually presents as an acute painful vulvar ulcer in young women. The etiology is unknown, although recent reports have associated it with the Epstein-Barr virus. The diagnosis is made by exclusion after ruling out sexually transmitted diseases, autoimmune causes, trauma, and other etiologies of genital ulcerations. We report a case of a young woman who developed flu-like symptoms and painful vulvar ulcers. Complementary examinations ruled out sexually transmitted diseases and the other usual causes of genital ulcers; lesions healed with no sequelae or recurrences. This case represents a rare important differential diagnosis of genital ulceration.
Case for diagnosis
Authors: Hammerschmidt Mariana , Azevedo Luciana Menezes de , Ruaro Anelisa , Werner Betina , Nascimento Alexandre do , Amaral Filho Ézio Augusto
Published: August 2012

Atypical fibroxanthoma is a rare cutaneous tumor found mainly in elderly people on sun-exposed areas of the body. Histologically, atypical fibroxanthoma is considered a malignant fibrous histiocytoma with bizarre neoplastic cells, marked pleomorphism, hyperchromatic nuclei and abundant mitoses. It must be differentiated from other skin tumors, usually by immunohistochemistry, since its diagnosis is made by exclusion.
Case for diagnosis
Authors: Tonoli Renata Elise , Souza Paulo Ricardo Martins
Published: August 2012

Chilblains are an inflammatory skin condition that develops following exposure to the cold. They consist of pruritic and/or painful erythematous-to-violaceous acral lesions and are the result of an abnormal vascular response to exposure to the cold. This benign condition is common in southern Brazil, particularly in Rio Grande do Sul where climatic conditions, together with cultural and economic aspects, facilitate the development of these sores.
Case for diagnosis
Authors: Thomé Emanuela Plech , Steglich Raquel Bissacotti , Meotti Carolina Degen , Schwartz Joel , Boff Ana Letícia
Published: August 2012

Papular elastorrhexis is a rare acquired disease, first described in 1987 by Bordas, which has been very rarely reported in the literature. It is characterized by small asymptomatic non-follicular papules, mainly distributed in the trunk. Histology of the lesions shows homogenization of collagen and fragmentation of elastic fibers in the dermis. The rarity of this disease is probably due to the subtlety and benign nature of clinical and histopathological alterations, which can be easily confused with other pathologies. The authors report the case of a patient with exuberant clinical manifestations typical of elastorrhexis papular.
Identificação e descrição de relações comportamentais na economia solidária
Authors: Cortegoso Ana Lucia
Published: August 2012

Que comportamentos, nas relações organismo-ambiente, fazem parte da economia solidária como organização para o trabalho e repercussão na sociedade? A partir de observação e registro de informações em situações de trabalho em uma incubadora universitária de empreendimentos solidários, consulta a documentos de atividades realizadas e literatura e entrevistas sobre aspectos da atuação de diferentes tipos de atores nesse campo de atividade humana, foi possível identificar e descrever comportamentos organizacionais e individuais. Tais comportamentos são considerados relevantes para práticas culturais cooperativas, distribuição eqüitativa dos benefícios do trabalho e relação menos predatória do homem com seu ambiente, inclusive social, em termos de relações ambiente-organismo. O produto deste estudo, como sistematização de atividades de uma agência universitária destinada a incubar empreendimentos solidários, representa contribuição para a compreensão do papel de diferentes atores sociais no complexo fenômeno social que é a economia solidária, a partir do conceito de comportamento como proposto pela análise do comportamento.
Vínculo e confiança em atendimento psicoterapêutico psicodramático grupal com presidiários
Authors: Gulassa Daniel
Published: August 2012

Este artigo discorre sobre experiências de atendimento a presos realizadas em instituições penitenciárias de Franco da Rocha, numa proposta psicoterápica grupal utilizando a metodologia do psicodrama. Busca-se demonstrar a importância de trabalhos dessa natureza, a partir de um foco na questão do vínculo terapêutico e da co-criação de vínculos de confiança. O relato, baseado na prática de atendimento a um grupo, caracterizado por quatorze encontros com onze detentos durante o segundo semestre de 2004, também considera a troca de experiências com colegas de trabalho, membros do grupo Mentes sem Grades. O desenvolvimento de vínculos de confiança possibilita novas experimentações de papéis, que podem estimular esperança, amor e talvez a superação de um ciclo que envolva isolamento e exclusão. O resultado do trabalho indica um aumento da tolerância dos presos em relação a sua própria condição, além de melhora nas relações interpessoais entre estes e também entre os não-presos.