30 research outputs found
Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3?.
Cardiac resynchronization therapy (CRT), the application of biventricular stimulation to correct discoordinate contraction, is the only heart failure treatment that enhances acute and chronic systolic function, increases cardiac work, and reduces mortality. Resting myocyte function also increases after CRT despite only modest improvement in calcium transients, suggesting that CRT may enhance myofilament calcium responsiveness. To test this hypothesis, we examined adult dogs subjected to tachypacing-induced heart failure for 6 weeks, concurrent with ventricular dyssynchrony (HFdys) or CRT. Myofilament force-calcium relationships were measured in skinned trabeculae and/or myocytes. Compared with control, maximal calcium-activated force and calcium sensitivity declined globally in HFdys; however, CRT restored both. Phosphatase PP1 induced calcium desensitization in control and CRT-treated cells, while HFdys cells were unaffected, implying that CRT enhances myofilament phosphorylation. Proteomics revealed phosphorylation sites on Z-disk and M-band proteins, which were predicted to be targets of glycogen synthase kinase-3beta (GSK-3beta). We found that GSK-3beta was deactivated in HFdys and reactivated by CRT. Mass spectrometry of myofilament proteins from HFdys animals incubated with GSK-3beta confirmed GSK-3beta-dependent phosphorylation at many of the same sites observed with CRT. GSK-3beta restored calcium sensitivity in HFdys, but did not affect control or CRT cells. These data indicate that CRT improves calcium responsiveness of myofilaments following HFdys through GSK-3beta reactivation, identifying a therapeutic approach to enhancing contractile function
Role of cardiac resynchronization therapy in the development of new-onset atrial fibrillation: A single-center prospective study.
Albeit several studies examined the association between cardiac resynchronization therapy (CRT) and atrial fibrillation (AF) in heart failure (HF), results are still unclear and quite conflicting. We thereby designed a single-center prospective study to determine whether CRT has a favorable effect on the incidence of new-onset AF in a homogeneous population of patients with non-ischemic idiopathic dilated cardiomyopathy and severe heart failure HF. We enrolled 58 patients, AF naïve when received CRT. After 1 year of follow-up our population was subdivided into responders (72.4%) and non (27.6%), so to compare the incidence of AF after 1, 2 and 3 years of follow-up in these two groups. Already after 1 year, there is a significant (p<0.05) difference in new-onset AF in non-responder patients respect to responders (18.2% vs 3.3%). These data are confirmed at 2 year (33.3% vs 12.2%) and 3 year (50.0% vs 15.0%) follow-up. In particular, at 3 year follow-up, non-responders have an increased risk to develop new-onset AF (OR=5.67, 95% confidence interval = 1.36-23.59, p=0.019). The present work suggests a possible favorable role of this non-pharmacological therapy, on the prevention of AF
Zero-inflated Poisson regression models for QTL mapping applied to tick-resistance in a Gyr x Holstein F2 population
Nowadays, an important and interesting alternative in the control of tick-infestation in cattle is to select resistant animals, and identify the respective quantitative trait loci (QTLs) and DNA markers, for posterior use in breeding programs. The number of ticks/animal is characterized as a discrete-counting trait, which could potentially follow Poisson distribution. However, in the case of an excess of zeros, due to the occurrence of several noninfected animals, zero-inflated Poisson and generalized zero-inflated distribution (GZIP) may provide a better description of the data. Thus, the objective here was to compare through simulation, Poisson and ZIP models (simple and generalized) with classical approaches, for QTL mapping with counting phenotypes under different scenarios, and to apply these approaches to a QTL study of tick resistance in an F2 cattle (Gyr x Holstein) population. It was concluded that, when working with zero-inflated data, it is recommendable to use the generalized and simple ZIP model for analysis. On the other hand, when working with data with zeros, but not zero-inflated, the Poisson model or a data-transformation-approach, such as square-root or Box-Cox transformation, are applicable
SISTEM PENGENDALIAN INTENSITAS CAHAYA PADA MINIATUR RUANG KULIAH MENGGUNAKAN KONTROLER PI BERBASIS ARDUINO
Pada penelitian ini, dibuat suatu perekayasaan kondisi lingkungan untuk pengendalian intensitas cahaya menggunakan miniatur ruang kuliah. Sensor yang digunakan adalah sensor BH1750. Sensor ini berfungsi untuk membaca intensitas cahaya yang masuk pada plant setelah di feedback oleh PWM(Pulse Width Modulation) dengan kontroler PI (Proportional Integral). Kontroler PI ini memiliki keunggulan seperti mempercepat respon sistem dan mengurangi offset. Proses perancangan kontroler PI menggunakan metode Hand Tuning dan didapatkan parameter PI yaitu Kp = 0,001, Ki=69. Pengendalian dirancang agar intensitas cahaya pada plant sesuai dengan setpoint yaitu 250 lux. Hasil pengujian terhadap keseluruhan sistem diperoleh error steady state sebesar 0,734% dan settling time sebesar 0,8855 detik. Percoban saat plant diberikan gangguan dengan sensor dihalang kertas putih membutuhkan recovery time selama 0,49 detik, sedangkan saat diberi gangguan cahaya tambahan membutuhkan recovery time selama 0,77 detik. Setelah mengalami gangguan, sistem yang menggunakan kontroler PI mampu kembali ke keadaan steady state. Kata Kunci: Pengendalian intensitas cahaya, sensor BH1750, Kontroler PI, Hand Tunin
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Fusion Approach to Finding Opinions in Blogosphere
In this paper, we describe a fusion approach to finding opinion about a given target in blog postings. We tackled the opinion blog retrieval task by breaking it down to two sequential subtasks: on- topic retrieval followed by opinion classification. Our opinion retrieval approach was to first apply traditional IR methods to retrieve on-topic blogs, and then boost the ranks of opinionated blogs using combined opinion scores generated by four opinion assessment methods. Our opinion module consists of Opinion Term Module, which identify opinions based on the frequency of opinion terms (i.e., terms that only occur frequently in opinion blogs), Rare Term Module, which uses uncommon/rare terms (e.g., “sooo good”) for opinion classification, IU Module, which uses IU (I and you) collocations, and Adjective-Verb Module, which uses computational linguistics’ distribution similarity approach to learn the subjective language from training data.This paper was presented by the author(s) at the International Conference on Weblogs and Social Media on March 27, 2007, in Boulder, Colorado, U.S.A. This paper has also been published as: Yang, K., Yu, N., Valerio, A., Zhang, H., & Ke, W. (2007). Fusion approach to finding opinionated blogs. Proceedings of the American Society for Information Science and Technology, 44(1), 1–14. doi: 10.1002/meet.1450440254Keywords: Opinion Identification, Method Fusion, Rank-boosting, Dynamic Tunin
Evaluation of the toxic effects of carbamates: I. Experimental model in Wistar rats and comparison with the intentional poisoning of cats and dogs; II. Analysis of the stability of the compounds and their effects in the immediate post mortem and in exhumed animals
A intoxicação intencional de animais e de pessoas é uma ameaça à saúde e à segurança públicas em todo o mundo. No Brasil, os pesticidas da classe dos carbamatos aldicarbe e carbofurano são facilmente obtidos, e uma única dose letal daqueles é facilmente misturada a alimentos palatáveis e iscas. Foram analisadas as necropsias de 26 gatos e 10 cães, da rotina do Serviço de Patologia Animal da FMVZ-USP, com variados intervalos post mortem e tipos de conservação de carcaça, intoxicados pelos carbamatos aldicarbe e carbofurano, confirmados pela cromatografia de camada delgada (CCD) e cromatografia líquida de alta performance com detector de arranjo de diodos (CLAE-DAD). Foram colhidas as matrizes biológicas para histopatologia e análise toxicológica. CLAE-DAD foi utilizada para detectar o aldicarbe e seus metabólitos, aldicarbe sulfóxido e aldicarbe sulfona, e carbofurano e seu metabólito 3-hidroxicarbofurano. As análises macroscópica e histopatológica revelaram predominantemente achados congestivos e hemorrágicos, o que pode ser resultante dos efeitos tóxicos dos carbamatos e seus metabólitos. Foram feitos 2 experimentos envolvendo exposição a uma dose única de carbofurano e de aldicarbe via gavagem em ratos Wistar. No primeiro, no qual foram avaliados os efeitos no post mortem imediato, 30 animais forma separados nos seguintes grupos: aldicarbe (n=10), carbofurano (n=10) e grupo controle (n=10). Os animais foram filmados para avaliar as alterações clínicas na intoxicação aguda e, quando foram sedados, foi colhido sangue por punção cardíaca para fazer o hemograma, bioquímica sérica, colinesterase e exame toxicológico e, após a eutanásia, foi feita a necropsia e colhido material para o exame histopatológico. Em todos os animais experimentais foi possível ser feita a detecção e a quantificação do aldicarbe e do carbofurano, além das alterações microscópicas congestivas e hemorrágicas, com alterações em parâmetros hematológicos e bioquímicos. No segundo experimento, foram utilizados 30 animais, e o protocolo experimental foi idêntico ao experimento anterior, exceto que, após o óbito, os animais foram colocados em uma caixa com terra nos seguintes grupos: 1 dia, 3 dias, 5 dias, 7 dias e 10 dias, e em cada dia foram agrupados 2 animais intoxicados e 1 controle, sendo que as necropsias foram feitas nestes intervalos. Foram colhidos cérebro, pulmão, fígado e rim ao exame histopatológico e globo ocular, conteúdo gástrico, fígado e músculo esquelético ao exame toxicológico. Foram observadas as alterações tanatológicas e, em todas as matrizes analisadas, puderam ser quantificados o aldicarbe e/ou seus metabólitos aldicarbe sulfóxido e aldicarbe sulfona, bem como o carbofurano e seu metabólito 3-hidroxicarbofurano. Estes estudos mostram a importância da necropsia e da coleta de matrizes diversas ao exame toxicológico, que são complementares e cruciais na investigação de óbitos decorrentes de intoxicações por praguicidas, tanto no post mortem imediato quanto em exumaçõesThe intentional poisoning of animals and people is a threat to public health and safety worldwide. In Brazil, the carbamate pesticides aldicarb and carbofuran are easily obtained. A single lethal dose of these carbamates is easily mixed with palatable food or baits. Necropsies and histopathological examinations of 26 cats and 10 dogs poisoned by the carbamates aldicarb and carbofuran were performed in the Service of Animal Pathology of FMVZ-USP, and the poisoning was confirmed by thin layer chromatography (TLC) and high performance liquid chromatography with diode-array detector (HPLC-DAD), with variable post mortem interval and conservation of the carcass. Biological matrices were collected for histopathological and toxicological analysis. HPLC-DAD was utilised to detect aldicarb and its metabolites, aldicarb sulphoxide and aldicarb sulphone, and carbofuran and its metabolite 3-hydroxycarbofuran. Gross and histopathological evaluations showed mainly congestive and haemorrhagic findings, which may result from the toxic effects of the carbamates and their metabolites. Two experimental protocols were performed in Wistar rats by exposing them to a single oral gavage dose to the carbamates aldicarb and carbofuran. The first experiment was performed to evaluate the immediate post mortem effects of carbamates, and 30 rats were divided into three groups: aldicarb (n-=10), carbofuran (n=10) and control (n=10). The animals were filmed to evaluate the clinical signs of poisoning, and they were sedated to collect blood by heart puncture, to perform CBC, serum biochemistry, and to measure serum cholinesterase. After euthanasia, tissues were collected for histopathological evaluation. Aldicarb and carbofuran were detected and quantified in the blood of all experimental groups, and the most common histological changes observed were congestion and haemorrhage. In the second experiment, the experimental protocol was identical to the first one, but the animals were buried in a plastic box with garden soil within 5 groups of 3 animals, two exposed to the same pesticide and 1 control, as follows: day 1, day 3, day 5, day 7 and day 10. The exhumations were performed within these days (1, 3, 5, 7 and 10). We collected brain, lung, liver and kidney to examine the thanatological changes, and the eyeballs, gastric content, liver and skeletal muscle to perform the toxicological screening. Thanatological changes could be observed within and between the groups, and, in all the matrices we could detect aldicarb and its metabolites aldicarb sulphoxide and aldicarb sulphone, and carbofuran and its metabolite 3-hydroxycarbofuran. The studies have shown the importance of the necropsy and the collection of diverse matrices to the toxicological screening, because both are complementary and crucial to the investigation of deaths by pesticides poisoning, even in exhumation, since we could evaluate the thanatological changes and correlate them to the action of the pesticides in the tissue
The self-maintaining nature of ventricular fibrillation : contribution of L-type Ca²+ channels and Na+/Ca²+ exchange to cardiomyocyte Ca²+ overload in ventricular fibrillation : surface fluorescence study in isolated perfused rat hearts
Approximately 40% of all deaths in Switzerland are due to cardiovascular diseases.1 An important part of these deaths happen because of life-threatening cardiac arrhythmias. Ventricular fibrillation (VF) is the most dangerous cardiac arrhythmia usually caused by ischemic heart disease and infarction. It also happens in apparently healthy individuals representing the most common cause of sudden death. The problem of high mortality associated with sudden cardiac death due to VF is relevant to all industrialized countries. In the United States, VF accounts for approximately 300,000 deaths per year.2 Currently the most important therapy is the implantable cardioverter-defibrillator (ICD). Recent clinical trials3 have expanded the indications for device therapy to overmillion patients in the US alone at a cost exceeding $50 billion if fully implemented.2 This consideration provides a strong motive to develop alternative new therapies that are comparably effective but less expensive and invasive.2 This requires a better understanding of VF pathogenesis at the molecular and cellular level. Therefore, our study was focused on elucidation of mechanisms of VF. It has been proposed that detrimental effects of VF are partially due to rapidly developing overload of cytosol of cardiac cells with Ca2+.4 The Ca2+ overload is responsible for maintaining of VF as well as for reinduction of VF after defibrillation5 and for the postVF left ventricular (LV) disfunction.6 It is not clear, however, through which pathways Ca2+ enters cells during VF. Here we studied the role of different ion transport systems, particularly, of L-type Ca2+ channels and sodium-calcium (Na+/Ca2+) –exchange, in initiation and maintenance of Ca2+ overload during VF. We applied drugs specifically blocking each of these Ca2+ transport systems in an isolated perfused rat heart model. We used nifedipine, a blocker of L-type Ca2+ channels and KB-R7943, a specific blocker of the reverse mode of Na+/Ca2+exchange. We induced VF in the hearts by rapid pacing and registered changes of intracellular Ca2+ concentration ([Ca2+]i) using surface fluorescence of the Ca2+ indicator indo-1. In order to get a better understanding of extend of Ca2+ overload during VF we calibrated fluorescence signal of indo-1 to [Ca2+]i. During the first two minutes of VF [Ca2+]i reached about double of the normal systolic concentration achieving ! 2000 -
2500 nM. With further VF duration [Ca2+]i elevated less rapidly and achieved ! 3000 nM.
We found that both L-type Ca2+ channels and Na+/Ca2+-exchange contribute to Ca2+
overload during VF. Specifically, when each of the drugs was perfused before VF
induction, nifedipine reduced the extend and especially the rate while KB-R7943 mostly
reduced the extend of Ca2+ accumulation in cardiomyocytes. Additionally, Na+/Ca2+-
exchange also contributes to maintenance of Ca2+ overload during VF because perfusion
of the hearts with KB-R7943 after VF has been induced also reduced [Ca2+]i. Finally, in
all groups of hearts perfused with the drugs, spontaneous terminations of VF
(defibrillations) were frequently observed. The spontaneous defibrillations did not happen
in untreated control hearts. These results enabled us to conclude that both L-type Ca2+
channels and Na+/Ca2+-exchange are important ways of Ca2+ entry into the
cardiomyocytes during VF. The L-type Ca2+ channels are more important for Ca2+ entry
into cardiomyocytes at the initial stage of VF. The Na+/Ca2+-exchange is also important at
the initial stage of VF but its contribution increases rapidly with progression of VF
Evaluation of Capacitive Deionization (CDI) on Nitrogen compounds and other water quality parameters in Recirculatory Aquaculture Systems (RASs) raising Atlantic salmon under two different organic loads
Recirculatory Aquaculture System (RAS) is an intensive fish farming technique that recirculates water used in the system after it is purified through the mechanical and biofilter. Maintaining water quality in RAS is essential including the removal of nitrogenous wastes through nitrification and denitrification.
Capacitive deionization (CDI) is a technology based on the electrochemical method that removes ions from water. Two different organic loads were created in three replicate microRAS systems by using 20 micrometer (µm) and 100 µm drum filter meshes respectively. Capacitive deionization (CDI) was tested for the removal of nitrogen compounds present in RAS water in the morning and the evening. The continuous effects of the CDI usage over eight hours on the RAS system were also tested.
A significant reduction in the level of alkalinity and conductivity was seen in the water treated by the CDI unit. Two instances of a significant reduction in nitrate (NO3-N) levels were also seen during the experiment. An increased level of nitrite (NO2-N) was detected after water was treated by the CDI unit. This might have occurred due to the voltage being used that might have caused the nitrification of ammonium ions or denitrification of nitrate to nitrite. Biofouling might have also occurred which could have caused the denitrification of nitrate to nitrite. Water treated through the CDI unit reduced ammonium (NH4-N) but was not statistically significant.
CDI has a high potential for ion removal from RAS systems, but fine-tuning of the CDI system is required for use in the RAS system.
Key words: Recirculatory aquaculture system , Capacitive deionization (CDI), Reduction , Nitrite increase, Fine tunin
Distribution of additive functions in algebraic number fields
1. Background. This thesis is based on ideas drawn from classical probabilistic number theory, from the work of Novoselov [2], and from the relevant work on algebraic number fields. Classical probabilistic number theory (as described in Elliott [1], for example) is concerned with the distribution of arithmetic functions on the ring of (rational) integers, ZZ. Two well-known results in this area are the Hardy-Ramanujan and the Erdos-Wintner theorems. The Hardy-Ramanujan theorem states that, in some sense, every integer n has about log log n prime divisors, and the Erdos-Wintner theorem gives conditions under·which additive functions have limiting distributions. The original proofs of both results were subsequently considerably simplified by using a result known as the Tunin-Kubilius inequality. Although results in this field have a definite probabilistic flavour, it has not proved easy to establish them by a direct appeal to the theory of probability. Novoselov [2] developed a probability space which provides a natural framework for developing results of probabilistic number theory from results of probability. For example, using standard results from probability theory and some arithmetic estimates (which amount to the Turan-Kubilius inequality) he obtained the Hardy-Ramanujan and Erdos-Wintner theorems. Many of the results of probabilistic number theory have been generalized to results concerning the distribution of additive functions on the ideals of the ring, V, of integers of an algebraic number field (see Prachar [3], for example). However, work in this area has not used a probabilistic framework as fully as in the classical case of ZZ. 2. Aims. The aim of this thesis is to set up a space for probabilistic number theory in algebraic number fields analogous to that of Novoselov [2] for ZZ and to apply his approach to develop analogues in 1) of the Hardy-Ramanujan and Erdos-Wintner theorems. We endeavour to produce as much as possible without the use of sieve results. 3. Contents Chapter 1 of this thesis is an introduction to the background outlined above, and Chapter 2 gathers together some preliminary material. In Chapter 3 we obtain an analogue of the Tunin-Kubilius inequality in D. For this purpose we estimate the number of elements of an ideal which lie in a multiple of the fundamental domain of D (viewed as a lattice). In Chapter 4 we construct a probability space Ω, containing D, using two different approaches. One approach is analogous to that in Novoselov [2). The other views n as the product of the completions of D with respect to its non-Archimedean valuations and this enables us to simplify some proofs. rn· Chapter 5 we prove versions of the Hardy-Ramanujan and ErdosWintner theorems for additive functions on the principal ideals of D. Some examples are discussed. In Chapter 6 we consider additive functions on all the ideals of 1) (not just the principal ideals). We prove Prachar's version of the Hardy-Ramanujan theorem (see Prachar [3]) by using the results of Chapter 5 and the correspondence between the ideals of D in a given class and certain elements of V. References [1] Elliott,P.D.T.A., Probabilistic number theory, Volumes I and 11. Springer-Verlag, New York (1979). [2] Novoselov,E.V., A new method in probabilistic number theory. Amer. Math. Soc. Translations (2) 52 (1966), pp. 217-275. (3] Prachar,K., Verallgemeinerung eines Satzes 'IJOn Hardy und Ramanujan auf algebraische Zahlkorper. Monatsh. Math. 56 (1952), pp. 229-232.Thesis (MSc) -- University of Adelaide, Dept. of Pure Mathematics, 198
