Modeling Front End Electronics for a Gas Electron Multiplier Detector

The Large Hadron Collider (LHC) in The European Organization for Nuclear Research (CERN) will have a Long Shutdown sometime during 2017 or 2018. During this time there will be maintenance and a possibility to install new detectors. After the shutdown the LHC will have a higher luminosity. A promising new type of detector for this high luminosity phase is a Triple-GEM detector. During the shutdown these detectors will be installed at the Compact Muon Solenoid (CMS) experiment. The Triple-GEM detectors are now being developed at CERN and alongside also a readout ASIC chip for the detector. In this thesis a simulation model was developed for the ASICs analog front end. The model will help to carry out more extensive simulations and also simulate the whole chip before the whole design is finished. The proper functioning of the model was tested with simulations, which are also presented in the thesis.

Urvilja : när livet är människans hem

This caring science study explores ‘Will’ as an ontological concept. The aim is to deepen the understanding of the essence of Will, and to highlight the manifestations of Will and how Will becomes evident in clinical caring. Will is ontological and universal. Will is connected with the essence of the human being, and manifests in the human being as will. The approach is inspired by Gadamer’s philosophical hermeneutics. The study’s horizon of understanding consists of Eriksson’s caritative theory and the caring science-tradition. The study’s research questions are as follows: What is the essence of Will? What are its manifestations? How does Will become evident in clinical caring? The hermeneutic interpretative movement is initiated by the material, which consists of the philosopher Arthur Schopenhauer’s texts, letters from experts and dictionaries. Meaning-bearing substance fragments in the material are intertwined with the original horizon of understanding through hermeneutical reading, hermeneutical interpretation and concept analysis in an oscillating interpretive movement. An abstraction occurs when the new substance is illuminated by the caring science ontology. The oscillating interpretive movement results in a reinterpreted horizon of understanding, which in turn provides the findings of the study. The reinterpreted horizon of understanding is presented in the form of a theoretical model and abductive theses. The essence of Will is represented in the theoretical model as the lifeaffirming and the loving force. Life and love are Will’s origin and destination. Will’s manifestations (its diversity) hold conditions and chance occurrences that obstruct Will. Hence the will of the human being does not necessarily appear in a way that is in tune with ontological Will. Will represents the lifeblood of ethos, and in this lifeblood love flows. Will acts by virtue of itself, and gives ethos its force. Will manifests in a way that ethos can affirm. When Will is affected by caring its force is active in the service of life and love. Being a caregiver entails acting as a world-eye, which means recognizing Will in diversity. For caregivers, being a world-eye means observing fragments of Will as it manifests in its original form in the real reality, and acting as the mirror of life. The human being who is able to perceive the fundamental values of life and to live according to these has understood the laws of life and entered upon the human calling. The human being then lives according to the fundamental order and has found a home in life.

Drömmen, resan och att finna sin plats : en hermeneutisk studie om vårdarens identitet

Bakgrund. Studien utgår ifrån antagandet att vårdaren är i en ständig utveckling av sin identitet och att utvecklingen påverkas av många olika faktorer. Forskningsöversikten visar att arbetsgemenskapen är av stor betydelse och att vårdarens identitet påverkas av olika erfarenheter och upplevelser. Det teoretiska perspektivet i denna studie är vårdvetenskapligt och den metodologiska ansatsen baserar sig på Gadamers hermeneutik. Syfte. Syftet med studien är att få en djupare förståelse för utvecklingen av vårdarens identitet samt att få en inblick i vilka faktorer som påverkar utvecklingen. Intresset riktas speciellt till arbetsgemenskapens och ensamhetens betydelse för utvecklingen. Metod. Materialet består av nio stycken av vårdare skrivna berättelser vilka har tolkats med hjälp av hermeneutisk tolkningsmetod. Den hermeneutiska tolkningsmetoden har inneburit en rörelse mellan helhet–delar–helhet och att den egna förförståelsen och traditionen har fått ta plats i tolkningen. Resultatet har framträtt när författaren och texterna nått en gemensam förståelse. Resultat. Vårdarens identitet formas av fyra element: 1. Ryggsäcken, det ”bagage” som vårdaren alltid bär med sig i alla situationer, såsom sin personlighet, tidigare erfarenheter och sin kunskap, 2. Patienten, d.v.s. att ha en vilja att vårda och en målsättning att ge god vård, 3. Arbetsmiljön och att finna sin plats i gemenskapen, 4. Vårdarens egen begrundan och reflektion. Om elementen inte helt kan uppfyllas försvagas identiteten. Att uppfylla alla element kan jämföras med att tillgodose vårdarens kroppsliga, själsliga och andliga aspekter. Resultatet visar också att arbetsgemenskapen och ensamheten har stor betydelse för identiteten. Vårdaren vill finnas i antingen en positiv arbetsgemenskap, som präglas av trygghet, tillit, respekt och arbetsglädje eller i en positiv ensamhet, där hon känner frihet och kan växa i sin roll. En del vårdare arbetar varierat med båda typerna av arbetsuppgifter. Båda arbetssätten stärker vårdarens identitet. Det som försvagar vårdarens identitet är negativ arbetsgemenskap, d.v.s. att känna att man inte passar in och att den egna utvecklingen hämmas eller negativ ensamhet, såsom känslor av totalt utanförskap i en arbetsgemenskap eller stor osäkerhetskänsla förorsakad av att man arbetar ensam. Negativ ensamhet kan ses som ett hot mot vårdarens identitet och liv. En stark identitet och att vara trygg i sin yrkesroll ska i förlängningen leda till en vilja hos vårdaren att ge god och kärleksfull vård.

Paul and death : a study in psychological coping

The present investigation looks into the attitudes toward death in Paul’s authentic letters, and puts them in relation to modern theories of psychological coping. Drawing on psychologically-oriented hermeneutic theory, and theories about psychological coping in particular, I argue that each case of psychological coping must be understood in its historical situation as strategies emanating from a specific person’s subjective appraisal (cf. Pargament, Lazarus and Folkman). Paul’s letters frequently refer to persecution and violent death. To aid in psychological coping is often integral to the purpose of the letters, which makes the perspective of psychological coping akin to their genre. In the course of a tentatively assumed chronological order of 1 Thessalonians, Galatians, 1 Corinthians, 2 Corinthians, Romans, Philippians, and Philemon, Paul moves from the perception of Jesus dying for the faithful to the understanding of dying with Jesus. His coping strategies concerning death are gradually transformed from conservative and deferring coping styles, to a more self-directing coping style, to collaborative and transformative coping styles, and finally to a new sense of deferring coping style in prison. The last case of deferring coping carries the traits of generosity and flexibility even in the face of death, which is in contrast to his previous letters. Through his correspondence, we see Paul’s attitude toward death transformed from denial to reaction, to processing, to acceptance (cf. Lindemann, Kübler-Ross, Bowlby, Parkes, among others). His strategies also shift in accordance with these understandings. Denial is accompanied by diversion, threat by aggression, processing by rumination, and acceptance by joy. The study shows the hermeneutic benefits of reading Paul’s letters as the rhetorically framed expressions of a person in a particular historical situation. The letters open small windows through which we can glimpse the coping process of a person of antiquity. In adopting the method of psychological exegesis, the study shows that the variety of attitudes toward death in Paul’s letters makes sense from the perspective of psychological coping. The psychological aspect of these letters is an underexamined richness that can extend into areas of contemporary individual and group identity, and from there to public policy and ethics.

Becoming a caring nurse : the heart of the matter in nurse education

This thesis in caring science didactics is based on a thinking, where the fundamental basis for the didactic is science-based, i.e. it does not emanate from the nursing profession but brings forward a didactic that grows out of caring science and its core substance and ethos. This view on didactics arises from the caritative theory developed by Eriksson. The overall aim of the study is to clarify the meaning and essence of understanding, as well as to explore and deepen the understanding of student nurses' processes of understanding and becoming with the intention of developing a theory model for caring didactics. The overarching research questions are: What is the essence of understanding (of caring science knowledge)? What are the possibilities and importance of understanding in the appropriation of caring science? What characterizes and impels the process of becoming? The thesis consists of four sub studies and a summary section. The overall methodological approach is hermeneutic involving quantitative as well as qualitative methods. The data for the study has been collected through a longitudinal research project that followed student nurses at three universities during their entire education. The empirical sub studies form the basis for the interpreted knowledge that is formulated in the new understanding. This new understanding have, through additional theory-charging with the theory fragments from Gadamer, generated the heuristic synthesis which is illustrated in the theory model. The findings shows that understanding can be described as something unlimited, as an endless movement, which can be illustrated as a lying eighth, a lemniscate. The lemiscate of understanding is characterized by seeing, knowing and becoming and consists of seven differently named phases; the acquired horizon of understanding, the encounter of horizons, the dialogue of horizons, the fusion of horizons, application, reflection and shaping a new horizon of understanding. Bildung (formation), is the ultimate imprint of the endless spiral movement of understanding. Ethos and arête constitute the hubs around which the lemniscate of understanding circles. These include the spirit and driving force that the student carries within. The caring culture encloses the lemniscate of understanding. The caring culture provides the life space of understanding and the prevailing basic values are evinced in the culture.

Livets källa kärleken : hälsans urkraft

This basic research focuses on the ethos of health and the human being's becoming in health. The theoretical perspective consists of the caring tradition within caring science developed at Åbo Akademy University. The aim of the present doctoral thesis is to uncover a new understanding as well as to deepen and attain a more nuanced understanding of the ethos of health, the essence of health, by penetrating to the core of what gives the human being the strength for experiencing a becoming in health. The research questions are as follows: l) What is the human being's source of strength? and 2) What reveals the source of strength so that the human being can perceive it and dedicate its strength in order to experience a becoming in health? The primary methodology used in the dissertation is hermeneutical. The material consists of the work Kärlekens gerningar by Kierkegaard, texts from focused interviews with respondents who have lived through severe personal suffering, as well as the book Det bländande mörkret by Wikström. These texts are interpreted through hermeneutical reading. The new horizon of understanding that emerges is reflected towards Eriksson's caritative theory, towards prior research within the tradition of caring science at Åbo Akademy University and towards previous national and international studies within this field. The new understanding shows that the human being's source of strength is love, the essence and origin of life. The substance of health is love, which, through the trinity of faith, hope and love, also makes possible the existence of the source of strength. Love has a deeper dignity than faith and hope, is connected with eternity and is the uniting link between temporality and eternity. The human being's inner longing entails an ontological attraction towards the source of strength. This source of strength is hidden, which provides and maintains its force, like a mystery connected with the darkness of suffering that hides the secret representing the source of strength, life's mystery, bu t w hi ch is revealed in both the darkness of suffering and in the light of joy. The dedication of strength requires freedom, willingness and courage to see the light, despite awareness of shame and guilt. Creative acts liberate the human being for the dedication of strength, which is preceded by a holy presence where, in solitude, the human being makes sacrifices for the sake of his or her human smallness and weakness, and allows himself or herself to be enclosed by the darkness of suffering to discover the light from the source. This entails being enraptured in a quiet "doing" in order to experience the beauty that bears witness to the holy which creates unity. The source of strength is revealed through beauty. The ethos of the human being and the ethos of health have the same fundamental substance, whilst the ethos of life possesses the deepest dimension and concerns the mysterious and infinite eternity. The ethos of life, eternity, which is a wellspring of strength, is not in itself strength-giving unless it is allied with love. Health can be understood in the light of life, of which death is an inevitable part. Life itself constitutes and creates the source which, through its alliance with eternity' s primordial wellspring of strength, generates strength from which the human being's source of strength, love, receives its eternal fervour. The human being is fundamentally interconnected with an abstract other, the first love, a universal wellspring of strength. Through Communion with this abstract other a dedication of the strength to experience a becoming in health becomes possible. Love for one's neighbour is the fundamental substance in the movement of becoming in health. Becoming in health presupposes a simultaneous movement in which the human being practices the human calling through ethos. As one loves one's neighbour through actions the still forces of eternity are in motion. When life emerges in the foreground and becomes the home of the human being, a dedication of the power of love is possible. Life itself determines the human being's becoming in health. A humble fundamental attitude towards life constitutes the basis for a continuous dedication of vitality from this source.

High incidence of adverse reactions to initial antiretroviral therapy in Brazil

A concurrent prospective study was conducted from 2001 to 2003 to assess factors associated with adverse reactions among individuals initiating antiretroviral therapy at two public referral HIV/AIDS centers in Belo Horizonte, MG, Brazil. Adverse reactions were obtained from medical charts reviewed up to 12 months after the first antiretroviral prescription. Cox proportional hazard model was used to perform univariate and multivariate analyses. Relative hazards (RH) were estimated with 95% confidence intervals (CI). Among 397 charts reviewed, 377 (95.0%) had precise information on adverse reactions and initial antiretroviral treatment. Most patients received triple combination regimens including nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. At least one adverse reaction was recorded on 34.5% (N = 130) of the medical charts (0.17 adverse reactions/100 person-day), while nausea (14.5%) and vomiting (13.1%) were the most common ones. Variables independently associated with adverse reactions were: regimens with nevirapine (RH = 1.78; 95% CI = 1.07-2.96), indinavir or indinavir/ritonavir combinations (RH = 2.05; 95% CI = 1.15-3.64), female patients (RH = 1.93; 95% CI = 1.31-2.83), 5 or more outpatient visits (RH = 1.94; 95% CI = 1.25-3.01), non-adherence to antiretroviral therapy (RH = 2.38; 95% CI = 1.62-3.51), and a CD4+ count of 200 to 500 cells/mm³ (RH = 2.66; 95% CI = 1.19-5.90). An independent and negative association was also found for alcohol use (RH = 0.55; 95% CI = 0.33-0.90). Adverse reactions were substantial among participants initiating antiretroviral therapy. Specially elaborated protocols in HIV/AIDS referral centers may improve the diagnosis, management and prevention of adverse reactions, thus contributing to improving adherence to antiretroviral therapy among HIV-infected patients.

Elevated amniotic fluid amino acid levels in fetuses with gastroschisis

Our objective was to measure maternal plasma and amniotic fluid amino acid concentrations in pregnant women diagnosed as having fetuses with gastroschisis in the second trimester of pregnancy. Twenty-one pregnant women who had fetuses with gastroschisis detected by ultrasonography (gastroschisis group) in the second trimester and 32 women who had abnormal triple screenings indicating an increased risk for Down syndrome but had healthy fetuses (control group) were enrolled in the study. Amniotic fluid was obtained by amniocentesis, and maternal plasma samples were taken simultaneously. The chromosomal analysis of the study and control groups was normal. Levels of free amino acids and non-essential amino acids were measured in plasma and amniotic fluid samples using EZ:fast kits (EZ:fast GC/FID free (physiological) amino acid kit) by gas chromatography (Focus GC AI 3000 Thermo Finnigan analyzer). The mean levels of essential amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) and non-essential amino acids (alanine, glycine, proline, and tyrosine) in amniotic fluid were found to be significantly higher in fetuses with gastroschisis than in the control group (P < 0.05). A significant positive correlation between maternal plasma and amniotic fluid concentrations of essential and nonessential amino acids was found only in the gastroschisis group (P < 0.05). The detection of significantly higher amino acid concentrations in the amniotic fluid of fetuses with a gastroschisis defect than in healthy fetuses suggests the occurrence of amino acid malabsorption or of amino acid leakage from the fetus into amniotic fluid.

Identification of characteristics for successful university-company partnership development

The importance of university-company collaboration has increased during the last decades. The drivers for that are, on the one hand, changes in business logic of companies and on the other hand the decreased state funding of universities. Many companies emphasize joint research with universities as an enabling input to their development processes, which aim at creating new innovations, products and wealth. These factors have changed universities’ operations and they have adopted several practices of dynamic business organizations, such as strategic planning, monitoring and controlling methods of internal processes etc. The objective of this thesis is to combine different characteristics of successful university-company partnership and its development. The development process starts with identifying potential partners in the university’s interest group, which requires understanding the role of different partners in the innovation system. Next, in order to find a common development basis, matching the policy and strategy between partners is needed. The third phase is to combine the academic and industrial objectives of a joint project, which is a typical form of university-company collaboration. The optimum is a win-win situation where both partners, universities and companies, can get addedvalue. For the companies added value typically means access to new research results before their competitors. For the universities added value offers a possibility to carry on high level scientific work. The research output in the form of published scientific articles is evaluated by the international science community. Because the university-company partnership is often executed by joint projects, the different forms of this kind of projects is discussed in this study. The most challenging form of collaboration is a semi-open project model, which is not based on bilateral activities between universities and companies but on a consortium of several universities, research institutes and companies. The universities and companies are core actors in the innovation system. Thus the discussion of their roles and relations to public operators like publicly funded financiers is important. In the Finnish innovation system there are at least the following doers executing strategies and policies: EU, Academy of Finland and TEKES. In addition to these, Strategic Centres for Science, Technology and Innovation which are owned jointly by companies, universities and research organizations have a very important role in their fields of business. They transfer research results into commercial actions to generate wealth. The thesis comprises two parts. The first part consists of an overview of the study including introduction, literature review, research design, synthesis of findings and conclusions. The second part introduces four original research publications.

Duodenal gastric metaplasia and Helicobacter pylori infection in patients with diffuse nodular duodenitis

Whether the regression of gastric metaplasia in the duodenum can be achieved after eradication of Helicobacter pylori is not clear. The aim of the present study was to investigate the relationship between H. pylori infection and gastric metaplasia in patients with endoscopic diffuse nodular duodenitis. Eighty-six patients with endoscopically confirmed nodular duodenitis and 40 control patients with normal duodenal appearance were investigated. The H. pylori-positive patients with duodenitis received anti-H. pylori triple therapy (20 mg omeprazole plus 250 mg clarithromycin and 400 mg metronidazole, all twice daily) for one week. A control endoscopy was performed 6 months after H. pylori treatment. The H. pylori-negative patients with duodenitis received 20 mg omeprazole once daily for 6 months and a control endoscopy was performed 2 weeks after treatment. The prevalence of H. pylori infection was 58.1%, and the prevalence of gastric metaplasia was 57.0%. Seventy-six patients underwent endoscopy again. No influence on the endoscopic appearance of nodular duodenitis was found after eradication of H. pylori or acid suppression therapy. However, gastric metaplasia significantly decreased and complete regression was achieved in 15/28 patients (53.6%) 6 months after eradication of H. pylori, accompanied by significant improvement of other histological alterations. Only mild chronic inflammation, but not gastric metaplasia, was found in the control group, none with H. pylori infection in the duodenal bulb. Therefore, H. pylori infection is related to the extent of gastric metaplasia in the duodenum, but not to the presence of diffuse nodular duodenitis.

Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20%, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20%. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin) instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU) measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays were correlated (P < 0.0001). Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001) and for diphtheria (r² = 0.93, P < 0.0001) between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Amniotic fluid amino acid levels in non-immune hydrops fetalis: a case-control study

In a prospective case-control study, we compared the amniotic fluid amino acid levels in non-immune hydrops fetalis (NIHF) and normal fetuses. Eighty fetuses underwent amniocentesis for different reasons at the prenatal diagnosis unit of the Department of Obstetrics and Gynecology, Faculty of Medicine, Dicle University. Forty of these fetuses were diagnosed with NIHF. The study included 40 women each in the NIHF (mean age: 27.69 ± 4.56 years) and control (27.52 ± 5.49 years) groups, who had abnormal double- or triple-screening test values with normal fetuses with gestational ages of 23.26 ± 1.98 and 23.68 ± 1.49 weeks at the time of sample collection, respectively. Amniotic fluid amino acid concentrations (intra-assay variation: 2.26-7.85%; interassay variation: 3.45-8.22%) were measured using EZ:faast kits (EZ:faast GC/FID free (physiological) amino acid kit; Phenomenex, USA) by gas chromatography. The standard for quantitation was a mixture of free amino acids from Phenomenex. The levels of 21 amino acids were measured. The mean phosphoserine and serine levels were significantly lower in the NIHF group, while the taurine, α-aminoadipic acid (aaa), glycine, cysteine, NH4, and arginine (Arg) levels were significantly higher compared to control. Significant risk variables for the NIHF group and odds coefficients were obtained using a binary logistic regression method. The respective odds ratios and 95% confidence intervals for the risk variables phosphoserine, taurine, aaa, Arg, and NH4 were 3.31 (1.84-5.97), 2.45 (1.56-3.86), 1.78 (1.18-2.68), 2.18 (1.56-3.04), and 2.41 (1.66-3.49), respectively. The significant difference between NIHF and control fetuses suggests that the amniotic fluid levels of some amino acids may be useful for the diagnosis of NIHF.

Clinicopathological significance of PTPN12 expression in human breast cancer

Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a recently identified tumor suppressor gene (TSG) that is frequently compromised in human triple-negative breast cancer. In the present study, we investigated the expression of PTPN12 protein by patients with breast cancer in a Chinese population and the relationship between PTPN12 expression levels and patient clinicopathological features and prognosis. Additionally, we explored the underlying down-regulation mechanism from the perspective of an epigenetic alteration. We examined PTPN12 mRNA expression in five breast cancer cell lines using semi-quantitative reverse-transcription PCR, and detected PTPN12 protein expression using immunohistochemistry in 150 primary invasive breast cancer cases and paired adjacent non-tumor tissues. Methylation-specific PCR was performed to analyze the promoter CpG island methylation status of PTPN12. PTPN12 was significantly down-regulated in breast cancer cases (48/150) compared to adjacent noncancerous tissues (17/150; P < 0.05). Furthermore, low expression of PTPN12 showed a significant positive correlation with tumor size (P = 0.047), lymph node metastasis (P = 0.001), distant metastasis (P = 0.009), histological grade (P = 0.012), and survival time (P = 0.019). Additionally, promoter CpG island hypermethylation occurs more frequently in breast cancer cases and breast cancer cell lines with low PTPN12 expression. Our findings suggest that PTPN12 is potentially a methylation-silenced TSG for breast cancer that may play an important role in breast carcinogenesis and could potentially serve as an independent prognostic factor for invasive breast cancer patients.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.