Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural actions of digitalis.

Neural actions of digitalis drugs have been well documented but their role in the cardiovascular effects of this group of agents is a subject of considerable con­ troversy. Information concerning neural actions of these drugs, as related to their cardiovascular effects, can be grouped into the following three categories: conduction, automaticity, and refractory period; ventricular arrhythmias; and inotropic and hemodynamic effects. The first are examples where firm evidence from both animal and human studies indicates a major role for the nervous system in determining the response produced by digitalis drugs. The second is an example where impressive evidence has been obtained from some but not all animal studies indicating an important role for the nervous system in the toxic response of these agents. The third are examples where present data suggest a role for the nervous system in the well-known actions of digitalis drugs on the heart and vasculature, but more experimentation is needed to confirm present findings and to further elucidate the extent to which the nervous system partici­ pates in these responses.
Type 2 Diabetes: Progress Made but Still a Long Road to Travel to Reduce Disease Burden

The basic concept of diabetes mellitus (DM) has undergone dramatic transformations by the application of systematic clinical research since the condition was first described thousands of years ago. The first transformation was from the social meaning of the diagnostic feature of the disease diabetes—the Greek term meaning “to pass through” and considered a disease of the kidneys because of frequent urination that characterized the disease to its current understanding as an endocrine disease. The second transformation was from the recognition that the feature of the disease has changed from one of predominant insulin deficiency, to one of predominant obesity with a combination of insulin resistance and impaired insulin secretion. An ongoing transformation in the disease, observed with the growing incidence of obesity in children, includes an increase in the diagnosis of type 2 diabetes in people <20 years of age. Diabetes mellitus comprises two major forms. Type 1 DM is an autoimmune disease in which the body destroys its pancreatic b cells, resulting in a lack of insulin production, whereas type 2 DM is primarily related to insulin resistance. The term “diabetes” was first coined by Apollonius of Memphis around 230 BC, although the characteristics of the disease had been described in Ebers Papyrus written approximately 1500 BC. The first complete clinical description of diabetes was attributed by many to Aulus Cornelius Celsus (30 BC 250 AD). In 1679, Thomas Willis used the sweet taste of diabetic urine to distinguish between DM and diabetes insipidus, and a century later, in 1776, Mathew Dobson showed that the sweetness of the urine from diabetics was because of the sugar content. He also showed that the presence of sugar in the urine was preceded and accompanied by increased sugar in the blood, the concept of hyperglycemia leading to glycosuria, which later became the hallmark for the detection of DM and also confirmed it as a systemic disease. Extensive experimental studies by Claude Bernard demonstrated that degeneration of the pancreas led to the development of DM and that the liver also stored glycogen, which could be released into the circulation. Insulin was finally discovered by Frederick Banting and Charles Best in 1921 as the active extract from the pancreatic islet cells of healthy dogs. The early assimilation of insulin into clinical practice represented a significant milestone for the rapid translation of discovery in basic science, to clinical therapeutics and benefit for patients. Drug treatment of DM has mirrored the understanding of the pathophysiology of the disease and its clinical transformation. From the experimental use of pancreatic extracts to the discovery of insulin and its
[Expression and clinical significance of MMP-2, MMP-9,TIMP-1, and TIMP-2 in breast carcinoma].

BACKGROUND & OBJECTIVE Expression imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play pivotal roles in tumor invasion and metastasis. But little is known about the correlation between their expression and breast cancer prognosis. The aim of this study was to investigate the expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 in breast carcinomas and to seek their relationship with breast cancer invasion, metastasis, and prognosis. METHODS Sixty-six patients of breast cancer with clinical features and survival data were enrolled. The mRNA expression of TIMP-2, MMP-2 were determined using in situ hybridization. The protein expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined using immunohistochemistry. The results were analyzed using chi-square test, Kaplan-Meier method, and Cox multivariate regression analysis. RESULTS The positive expression rates of TIMP-2 mRNA, MMP-2 mRNA and MMP-2, MMP-9, TIMP-1, and TIMP-2 protein were 66.7% (44/66), 65.2% (43/66) and 71.2% (47/66), 68.2% (45/66), 40.9% (27/66), 69.7% (46/66), respectively. The expression of MMP-2 protein had positive correlation with those of MMP-2 mRNA and MMP-9 protein(P< 0.01). The expression of TIMP-2 mRNA had positive correlation with that of TIMP-2 protein. Negative correlation between expression of TIMP-1 protein and MMP-9 protein was found (P< 0.01). Overexpression of MMP-2 and MMP-9 protein were higher in breast cancers with lymph node metastases than those without lymph node metastases, whereas TIMP-2 mRNA and TIMP-1 protein expression were lower in breast cancers with lymph node metastases than those without lymph node metastases (P< 0.05). MMP-2 mRNA and MMP-9 protein were positively associated with the tumor size and shortened survival time(P< 0.05, P< 0.01). Increased expression of MMP-9 protein was correlated with high TNM classification(P< 0.01). The patients of menopause and ER negative expression had higher expression of MMP-2 mRNA (P< 0.05). Kaplan-Meier analysis showed that MMP-2 mRNA, MMP-2 and MMP-9 proteins were linked with unfavorable prognosis(P< 0.01,P< 0.05). CONCLUSION Overexpression of MMP-2, MMP-9 and expression imbalance between MMP-9 and TIMP-1 protein might play critical roles in degradation of extracellular matrix to enhance the invasive and metastatic capacity of breast cancer. MMP-2 protein might be applied as an independent prognostic indicator for primary breast cancer.
Onchocerciasis: the Role of Wolbachia Bacterial Endosymbionts in Parasite Biology, Disease Pathogenesis, and Treatment

SUMMARY The discovery of Wolbachia intracellular bacteria within filarial nematodes, including Onchocerca volvulus, the causative agent of onchocerciasis or “river blindness,” has delivered a paradigm shift in our understanding of the parasite's biology, to where we now know that the bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms. The apparent mutualistic dependency has also offered a novel approach to the treatment of onchocerciasis through the use of antibiotics to eliminate Wolbachia, delivering for the first time a treatment which has significant macrofilaricidal efficacy. Studies with other filarial nematode species have also highlighted a role for Wolbachia in transmission and infection of the mammalian host through a fascinating manipulation of mast cell-mediated vasodilation to enhance infectivity of vector-borne larvae. Wolbachia has also been identified as the principal driver of innate and adaptive Th1 inflammatory immunity, which can either contribute to disease pathogenesis or, with the Wolbachia-mediated recruitment of mast cells, enhance infectivity. The Wolbachia activation of innate inflammation also drives inflammatory adverse events in response to chemotherapy with either diethylcarbamazine (DEC) or ivermectin. In this review we summarize the experimental and field trial data which have uncovered the importance of Wolbachia symbiosis in onchocerciasis.
Lawrence Berkeley National Laboratory Lawrence Berkeley National Laboratory Title Atomic resolution phase contrast imaging and in-line electron holography using variable voltage and dose rate

The TEAM 0.5 electron microscope is employed to demonstrate atomic resolution phase contrast imaging and focal series reconstruction with acceleration voltages between 20 and 300 kV and a variable dose rate. A monochromator with an energy spread of ≤0.1eV is used for dose variation by a factor of 1,000 and to provide a beam-limiting aperture. The sub-Ångstrøm performance of the instrument remains uncompromised. Using samples obtained from silicon wafers by chemical etching, the [200] atom dumbbell distance of 1.36 Å can be resolved in single images and reconstructed exit wave functions at 300, 80, and 50 kV. At 20 kV, atomic resolution < 2 Å is readily available but limited by residual lens aberrations at large scattering angles. Exit wave functions reconstructed from images recorded under low dose rate conditions show sharper atom peaks as compared to high dose rate. The observed dose rate dependence of the signal is explained by a reduction of beam-induced atom displacements. If a combined sample and instrument instability is considered, the experimental image contrast can be matched quantitatively to simulations. The described development allows for atomic resolution TEM of interfaces between soft and hard materials over a wide range of voltages and electron doses.
Size and strength of the quadriceps muscles of old and young women *

Abstract. Muscle weakness and wasting may be evaluated objectively by dynamometry and compound ultrasound imaging. We have measured the voluntary isometric strength of the quadriceps muscles of healthy women in their 70s (n= 25) and in their 20s (n= 25) and have compared it with the mid‐thigh cross‐sectional area of the same muscles.
A critical period in the sensitivity of basal forebrain cholinergic neurones to NGF deprivation

CHOLINERGIC neurones of basal forebrain (BF) express receptors for nerve growth factor (NGF) and are sensitive to NGF. In many CNS structures, including the BF region, the expression of NGF and its receptors is developmentally regulated. To test whether BF neurones depend on NGF during restricted time windows of postnatal development, we antagonized endogenous NGF by implanting, in the lateral ventricle of the rat, hybridoma cells producing blocking antibodies specific for NGF. Implants were performed at postnatal day 2 (P2), P8 and P15. BF cholinergic neurones were drastically reduced in number only when endogenous NGF was antagonized during the first postnatal week. We conclude that BF cholinergic neurones are sensitive to NGF deprivation only during early postnatal development.
The Role of Particle Composition on the Association Between PM2.5 and Mortality

Background: Although the association between exposure to particulate matter (PM) mass and mortality is well established, there remains uncertainty about which chemical components of PM are most harmful to human health. Methods: A hierarchical approach was used to determine how the association between daily PM2.5 mass and mortality was modified by PM2.5 composition in 25 US communities. First, the association between daily PM2.5 and mortality was determined for each community and season using Poisson regression. Second, we used meta-regression to examine how the pooled association was modified by community and season-specific particle composition. Results: There was a 0.74% (95% confidence interval = 0.41%–1.07%) increase in nonaccidental deaths associated with a 10 &mgr;g/m3 increase in 2-day averaged PM2.5 mass concentration. This association was smaller in the west (0.51% [0.10%–0.92%]) than in the east (0.92% [0.23%–1.36%]), and was highest in spring (1.88% [0.23%–1.36%]). It was increased when PM2.5 mass contained a higher proportion of aluminum (interquartile range = 0.58%), arsenic (0.55%), sulfate (0.51%), silicon (0.41%), and nickel (0.37%). The combination of aluminum, sulfate, and nickel also modified the effect. These species proportions explained residual variability between the community-specific PM2.5 mass effect estimates. Conclusions: This study shows that certain chemical species modify the association between PM2.5 and mortality and illustrates that mass alone is not a sufficient metric when evaluating health effects of PM exposure.
A Review of Covering Arrays and Their Application to Software Testing

Problem statement: As a complex logic system, software may suffer from different source of faults. Those faults can be avoided by applying different testing processes. It appears recently th at the interaction among the system factors represents a common source of faults. Software function properly, all input factors and their interactions of the software need to be tested i.e., exhaustive testing. Random testing, in another hand, doesn't g uarantee the coverage of all factors interaction. Approach: Covering Arrays (CAs) are mathematical objects used as platform or structure to represent the interactions of factors for a given system. The uses of CAs become important to reduce the test cases by covering all t-interactions of the system factors at least one time. Results: This study focuses exclusively on the applications of the CAs in softw are interaction testing. We provide an overview of CAs notations, types and construction methods. Conclusion: We reviewed the recent applications of CAs to software testing and discuss the future poss ible directions of the research. The research in th is area seems to be an active research direction for t he coming years.
Perfis de jogadores em contextos de ensino/aprendizagem em disciplinas de programação

Podem ser encontrados facilmente na literatura trabalhos que investigam se o uso ou a construcao de jogos em contextos educacionais gera beneficios ao aprendizado. Alem destes, tambem vem se tornando bastante comum a Gamificacao de ambientes de ensino. Neste artigo, apresentamos um experimento realizado com o intuito de verificar se perfis de jogadores podem ser utilizados como meio para agrupar usuarios/alunos em contextos educacionais. Um perfil de jogador pode ser descrito como a maneira que um individuo se relaciona com o jogo. No experimento realizado foram utilizados questionarios para identificacao de perfis, sendo um destes um ambiente descrito como um jogo e outro em um ambiente educacional. Os perfis identificados foram entao comparados utilizando como metrica o Kappa de Cohen. Os resultados obtidos demonstraram uma concordância substancial ($Kappa = 0.657$) entre as classificacoes obtidas. Como contribuicao, dados os resultados, e sugerido que um perfil de jogador possa ser utilizado em ambientes educacionais visando otimizar os ambientes para cada diferente perfil de jogador.
A reply

References 1. Kim HC, Yoo DH, Kim HJ, Jeon YT, Hwang JW, Park HP. A prospective randomised comparison of two insertion methods for i-gel placement in anaesthetised paralysed patients: standard vs rotational technique. Anaesthesia 2014; 69: 729–34. 2. Weber U, Oguz R, Potura LA, Kimberger O, Kober A, Tschernko E. Comparison of the i-gel and the LMA-Unique laryngeal mask airway in patients with mild to moderate obesity during elective shortterm surgery. Anaesthesia 2011; 66: 481–7.
Alterations in bone quality after socket preservation with grafting materials: a systematic review.

PURPOSE While the ability of various grafting materials to preserve extraction socket morphology has been adequately reviewed, the quality of the grafted bone in the socket is not as well understood. This systematic review aimed to compare the proportion of vital bone and connective tissue between grafted and naturally healed sockets. MATERIALS AND METHODS An electronic search of five databases (from 1965 to November 2011) and a hand search of peer-reviewed journals for relevant articles were performed. Human clinical trials that compared histologic components of soft and hard tissues in augmented sockets and naturally healed sites, with at least five samples per group, were included. RESULTS Eight studies (five randomized controlled trials and three controlled clinical trials) were included. The mean percentages of vital bone and connective tissue in natural healing sockets were 38.5% ± 13.4% and 58.3% ± 10.6%, respectively. Limited evidence (one to two articles for each material) implied that vital bone fraction was not different with demineralized allografts and autografts and increased by 6.2% to 23.5% with alloplasts in comparison to nongrafted sites. Four studies investigating the effect of xenografts were available, with equivocal results. The difference in the mean percentage of vital bone ranged from -22.2% (decrease) to 9.8% (increase). Connective tissue content decreased with the use of the aforementioned bone substitutes. Considerable residual hydroxyapatite and xenograft particles (15% to 36%) remained at a mean of 5.6 months after socket augmentation procedures. CONCLUSIONS Based on a limited number of prospective comparative studies, the use of grafting materials for socket augmentation might change the proportion of vital bone in comparison to sockets allowed to heal without grafting. Whether these changes in bone quality will influence implant success and peri-implant tissue stability remains unknown.
Investigation of glutamine and GABA levels in patients with idiopathic generalized epilepsy using MEGAPRESS

Idiopathic generalized epilepsies (IGE) comprise a group of clinical syndromes associated with spike wave discharges, putatively linked to alterations in neurotransmission. The purpose of this study was to investigate whether patients with IGE have altered glutamine and γ‐aminobutyric acid (GABA) levels indicative of altered excitatory and inhibitory neurotransmission in frontal regions.
Chimeric HIV‐1 and HIV‐2 lentiviral vectors with added safety insurance

Lentiviruses are unique in their ability to infect both dividing and non‐dividing cells. This makes the vectors derived from them particularly useful for gene transfer into non‐dividing cells, including stem cells. Lentiviral vectors are becoming the vectors of choice for si/shRNA delivery. The utility of the lentiviral vectors will be enhanced if additional elements of safety are built into their design. One safety concern is the generation of replication competent virus by recombination. We reasoned that HIV‐1 and HIV‐2 hybrid or chimeric lentiviral vectors will have added safety insurance in this regard. This is based on the premise that HIV‐1 and HIV‐2 are dissimilar enough in sequence to curtail recombination, yet similar enough to complement functionally. For hybrid vectors, we found that both HIV‐1 and HIV‐2 transfer vector RNAs could be packaged to equivalent titer by the HIV‐1 packaging machinery. However, HIV‐2 packaging machinery was unable to package HIV‐1 transfer vector as well as it did HIV‐2 transfer vector. This non‐reciprocacity suggested that the requirement for HIV‐2 vectors was more stringent and that for HIV‐1 vectors more promiscuous. When the HIV‐1 transfer vector was packaged with the chimeric packaging construct where the leader‐gag region of HIV‐2 was replaced with that of HIV‐1 packaging construct, the titer of the vector went up. This suggests that at least some of the determinants of specificity for vector assembly reside in the leader‐gag region. Incorporation of central polypurine tract (cPPT) and woodchuck post‐transcriptional enhance element (WPRE) into the HIV‐2 vectors had only modest effect on vector titer. Thus, chimeric lentiviral vectors with added safety features can be designed without compromising transduction efficiency. J. Med. Virol. 79:118–126, 2007. © 2006 Wiley‐Liss, Inc.
A loosely coupled MEMS-SINS/GNSS integrated system for land vehicle navigation in urban areas

Integrating Micro-Electro Mechanical System-Inertial Measurement Unit (MEMS-IMU) with Global Navigation Satellite System (GNSS) has been a widespread method to achieve cost-effective navigation solution for land vehicles. However, due to the significant and time-varying errors inherent to MEMS inertial sensors, the performance of Strapdown Inertial Navigation System (SINS) based on MEMS-IMU would degrade quickly during the frequent GNSS outages in urban environments. To improve the overall navigation accuracy, this paper proposed a combination of the following two approaches for the loosely coupled integrated system: (1) using the MEMS error coefficients derived from Allan variance analysis for Kalman filter (KF) tuning; and (2) providing additional measurements based on the knowledge of vehicle kinematic features for SINS error correction. In the second method, body velocity constraint and an improved zero velocity updates (ZUPT) method assisted by accelerometers are described. Road tests utilizing an automated vehicle in urban areas demonstrate the effectiveness of the proposed algorithms for reducing the rapid SINS drifts during GNSS outages.
Empirical Evaluation of Approaches to Testing Applications without Test Oracles

Software testing of applications in fields like scientific computing, simulation, machine learning, etc. is particularly challenging because many applications in these domains have no reliable “test oracle” to indicate whether the program’s output is correct when given arbitrary input. A common approach to testing such applications has been to use a “pseudo-oracle”, in which multiple independently-developed implementations of an algorithm process an input and the results are compared: if the results are not the same, then at least one of the implementations contains a defect. Other approaches include the use of program invariants, formal specification languages, trace and log file analysis, and metamorphic testing. In this paper, we present the results of two empirical studies in which we compare the effectiveness of some of these approaches, including metamorphic testing and runtime assertion checking. These results demonstrate that metamorphic testing is generally more effective at revealing defects in applications without test oracles in various application domains, including non-deterministic programs. We also analyze the results in terms of the software development process, and discuss suggestions for both practitioners and researchers who need to test software without the help of a test oracle.