Miracle-dz/UniFAR-FTUs huggingface dataset:
MMP-15 Is Upregulated in Preeclampsia, but Does Not Cleave Endoglin to Produce Soluble Endoglin

Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15–phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity–also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03) up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8) compared to gestationally matched preterm controls (n = 8). However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.
Projeto de banco de dados de simulações numéricas

Resumo. Com a rápida evolução dos sistemas computacionais, simulações numéricas baseadas em modelagem computacional têm alcançado soluções cada vez mais realistas. Ainda assim, o processo de simulação é complexo, exigindo grande capacidade computacional e produzindo muitos arquivos auxiliares com os resultados das simulações. Uma grande quantidade de arquivos, como os produzidos durante o processo de varredura de parâmetros, torna a gerência de experimentos uma tarefa bastante complexa, que associado ao cálculo da simulação, analisam seus resultados com programas espećıficos que precisam ser constrúıdos e que fazem acesso ineficiente aos arquivos, muitas vezes em texto bruto. Por outro lado, a adoção de sistemas de gerência de bancos de dados (SGBD) em apoio à simulações numéricas traz seus próprios desafios. A representação de domı́nios espaço-temporal e de variáveis que representam quantidades f́ısicas se mostra adequada para o armazenamento e consulta a esses tipos de dados. Neste contexto, este trabalho visa preencher uma lacuna existente na direção da adoção de SGBDs para o tratamento de dados de simulações numéricas. O focos deste trabalho está no processo de projeto do bancos de dados. Identifica-se, a partir do processo de projeto tradicional de banco de dados, extensões necessárias que permitem mapear o modelo conceitual de uma aplicações de simulação numérica em um projeto que combina modelo de dados relacional com modelo de matrizes multidimensionais. Apresenta-se um exemplo de aplicação de simulação do sistema cardiovascular humano e o processo de projeto de banco de dados implementado no sistema SciDB. Este trabalho tem como objetivo definir as fases de um projeto para o armazenamento de dados gerados por simulações numéricas, demonstrando a necessidade do armazenamento destes dados em array multidimensionais e o uso de técnicas tradicionais durante o processo de projeto do banco de dados. O conjunto de dados é representado através do uso do SciDB, que utiliza um modelo de dados em matrizes multidimensionais como a base de sua representação.
Centromedian–Thalamic and Hippocampal Electrical Stimulation for the Control of Intractable Epileptic Seizures

Summary The following two different modulatory procedures to control intractable epileptic seizures are presented: (1) chronic electrical stimulation of the centromedian–thalamic nucleus (ESCM) for control of generalized tonic–clonic seizures and atypical absences, and (2) subacute hippocampal stimulation (SAHCS) and chronic hippocampal stimulation for control of nonlesional temporal lobe seizures. The ESCM antiepileptic effect seems to be the result of activation of a nonspecific reticulothalamocortical system responsible for generalized electrocortical responses (recruiting, desynchronization, negative direct current shifts, and three spike–wave complexes per second). The success of the ESCM procedure depends on the following predictor factors: case selection (primary and secondary tonic–clonic seizures and atypical absences of the Lennox Gastaut syndrome), ventriculographic and electrophysiologic definition of the optimal stereotactic targets (based on the anterior commissure, posterior commissure, and the vertical line perpendicular to the posterior commissure and electrocortical recruiting responses), periodic electrophysiologic monitoring of the reliability of ESCM in the absence of the patient’s subjective sensations and with totally internalized subcutaneous stimulation systems (by recording scalp electrocortical recruiting, desynchronizing, and direct current responses), quantitative evaluation of clinical and EEG improvement, and analysis of the ON and OFF effects, taking into account a long-lasting (possibly plastic) effect of ESCM. SAHCS blocks clinical and EEG signs of temporal lobe epileptogenesis with no additional damage of the stimulated hippocampal tissue. Preliminary results suggest that this antiepileptic effect is, at least in part, the result of a physiologic inhibition of the stimulated hippocampal tissue, because after SAHCS the authors found the following: (1) increased threshold and decreased duration, propagation, and blockage of the clinical signs accompanied with the hippocampal afterdischarge; (2) flattening of the hippocampal-evoked response recovery cycles; (3) single photon emission computed tomographic hypoperfusion; and (4) increased concentration of benzodiazepine receptor binding at the stimulated hippocampal region. Chronic hippocampal stimulation persistently blocked temporal lobe epileptogenesis in one patient under open protocols during 24 months with no apparent additional alterations in recent memory.
A Test-Data Management Function for Chronic Condition Patients

The number of chronic condition patients has increased rapidly in recent years, with the result that an efficient diagnosis and treatment of these patients is required. Therefore, the attainment of a function that can diagnose chronic condition patients efficiently is the goal of computerized medical treatment. This paper describes "FUJI-Viewer", a clinical decision support system that pays attention to the flow of information for chronic condition patients. FUJI-Viewer creates a test plan for each patient, and manages patient's test plan over time in a consistent manner. FUJI-Viewer also prevents test-item omission errors and duplicate-item errors. The result of integrating these functions in an order entry system and its evaluation is described.
Contrastive Studies as Methodology: An example with the pragmatics of apology and thanks

Contrastive studies can be said to be one of the important methodologies to discover the universality and unique of languages and or language education. Nevertheless, if the objects of comparison are not chosen carefully, the exercise will just simply become a list of similarities and differences. This paper introduces examples of typological classification at the pragmatics level, and argues for contrastive methodology in contrastive studies that analyze speech acts set of apology and thanking.
Receptor-G protein signaling in yeast.

In this review we discuss the components and regulation of a G protein-linked signaling pathway in the yeast Saccharomyces cerevisiae. Studies of signal transduction in yeast permit rigorous genetic, physiological, and biochemical criteria to be applied for understanding receptor and G protein action. The study of receptor-G protein signaling in the yeast system can reveal novel principles and unique insights not accessible by studies of G protein-linked signaling systems in vertebrates. Here we review evidence that the oligopeptide mating pheromones of yeast act via a G protein-linked signal transduction pathway. Emphasized are the striking similarities in mechanism and regulation of receptor-G protein signal­ ing between yeast and higher eukaryotes. We include newly emerging evi­ dence that suggests mechanisms previously unidentified in other organisms regulate the G protein-mediated signaling pathway of yeast. There still are certain gaps in our current knowledge of the yeast G protein-linked signaling pathway. For this reason, we suggest plausible hypotheses to explain these uncertainties that can be scrutinized by further investigation. We have omitted detailed discussions of the general physiology and genetic regulation of yeast mating and the processing and secretion of oligopeptide
SPM management using Markov chain based data access prediction

Leveraging the power of scratchpad memories (SPMs) available in most embedded systems today is crucial to extract maximum performance from application programs. While regular accesses like scalar values and array expressions with affine subscript functions have been tractable for compiler analysis (to be prefetched into SPM), irregular accesses like pointer accesses and indexed array accesses have not been easily amenable for compiler analysis. This paper presents an SPM management technique using Markov chain based data access prediction for such irregular accesses. Our approach takes advantage of inherent, but hidden reuse in data accesses made by irregular references. We have implemented our proposed approach using an optimizing compiler. In this paper, we also present a thorough comparison of our different dynamic prediction schemes with other SPM management schemes. SPM management using our approaches produces 12.7% to 28.5% improvements in performance across a range of applications with both regular and irregular access patterns, with an average improvement of 20.8%.
The Relationship Between Inhibitory Control and Free Will Beliefs in 4-to 6-Year-Old-Children

This study explores the relationship between beliefs about self-control and the ability to exercise self-control in 4to 6year-old children. Sixty-eight children were asked a series of questions to gauge whether they believed that they could freely choose to act against their desires or inhibit themselves from performing desired actions. Children were also asked to provide qualitative explanations for why they could or could not exercise free will, and to complete two inhibitory control tasks: forbidden toy and day/night. Choice responses were negatively correlated with performance on the forbidden toy task, when children performed that task first. There was also a negative correlation between a belief in an internal locus of control, and success on the forbidden toy measure. Refraining from touching a forbidden toy appears to be correlated to less belief in free will. Though this may appear counter-intuitive, it is consistent with cross-cultural research.
Mental representations and Cognitive Science: excessive dependency and problems

Since the notions of representation and computation are in the center of the theoreticalconceptual framing and in the actual reproductions and simulations in cognitive science, we intend, in this paper, to discuss the problems concerning the notion of representation with respect to the simulations and / or reproductions of thought devices in artificial intelligence and connectionist networks. In this sense, we emphasize what we believe to be the main problem regarding the implementation of "smart" properties in non-biological devices, namely, the problem of structure, or “frame problem”, which can be described as the problem of how to develop and sustain an internal model of the world, so that we can implement trivial tasks such as crossing a busy street without getting hit or frying an egg efficiently, for example. © Cien. Cogn. 2010; Vol. 15 (2): 070-076.
Effects on Bacillus subtilis of a conditional lethal mutation in the essential GTP-binding protein Obg

The obg gene is part of the spo0B sporulation operon and codes for a GTP-binding protein which is essential for growth. A temperature-sensitive mutant in the obg gene was isolated and found to be the result of two closely linked missense mutations in the amino domain of Obg. Temperature shift experiments revealed that the mutant was able to continue cell division for 2 to 3 generations at the nonpermissive temperature. Such experiments carried out during sporulation showed that Obg was necessary for the transition from vegetative growth to stage 0 or stage II of sporulation, but sporulation subsequent to these stages was unaffected at the nonpermissive temperature. Spores of the temperature-sensitive mutant germinated normally at the nonpermissive temperature but failed to outgrow. The primary consequence of the obg mutation may be an alteration in initiation of chromosome replication.
Direct monitoring of energy lost due to soiling on first solar modules in California

The optical loss caused by the accumulation of dirt and other contaminants on solar collectors is the third most important meteorological input, after insolation and air temperature, that determines energy yield in a photovoltaic power plant. First Solar is monitoring the impact of dust accumulation on solar panels using a methodology similar to that proposed by Ryan and colleagues in a long-term study in Eugene, OR. The method seeks to be a practical and automated technique for measuring the soiling rate, foregoing complex equipment such as I(V ) curve tracers, and eliminating other performance-influencing factors. The test setup includes several First Solar plane-of-array modules that are allowed to accumulate natural contaminants, and several controls held clean by regular washing. This study reveals clear region-specific soiling trends as well as insight into the amount of rainfall required for full recovery of module performance. Soiling rates of up to 11.5% per month are observed in heavy agricultural areas. As little as 0.5 mm of rainfall is sufficient to completely clean a dirty frameless module in regions with lighter soiling rates.
The metabolism of carbamazepine in humans: steric course of the enzymatic hydrolysis of the 10,11-epoxide.

Carbamazepine 10,11-oxide (1a,10b-dihydro-6H-dibenzo[b,f]oxireno[d]azepine-6-carboxamide), a key intermediate in carbamazepine metabolism, was found to be unusually resistant to enzymatic hydrolysis when incubated with microsomal and cytosolic fractions from rabbit, rat, and guinea pig livers. However, its hydrolysis product, trans-10,11-dihydro-10,11-dihydroxy-5H-dibenzo[b,f]azepine-5-carboxamide , was excreted, as previously reported, both in the free and in conjugated forms, as the main metabolite in the urine of humans under carbamazepine treatment. The free diol and that obtained after treatment with beta-glucuronidase/arylsulfatase were both found by Mosher's method to be formed in an enantiomeric excess of 80%, the prevalent enantiomer having the (-)-10S,11S absolute configuration, as determined by applying the CD exciton coupling method to its bis[p-(dimethylamino)benzoyl] ester. This finding confirms the pronounced enantioselectivity of the microsomal epoxide hydrolase toward meso and racemic substrates, but is in contrast with the prevalent formation of (R,R)-diols in most other known cases of enzymatic hydrolysis of epoxides. Preparatively useful syntheses of the racemic trans-10,11-dihydro-10,11-diol and of 9-(hydroxymethyl)-10-carbamoylacridan, another carbamazepine metabolite, are reported for the first time.
3D mid-air manipulation techniques above stereoscopic tabletops

Stereoscopic tabletops collocate both user interaction and visualization spaces, fostering more natural freehand interaction metaphors to manipulate 3D virtual content. Thanks to a non-intrusive tracking solution, based on depth cameras, users can interact and manipulate virtual objects using both hands. In this position paper, we perform a comparative study of one multi-touch and four mid-air interaction techniques assigning the seven degrees of freedom (translation, rotation and uniform scaling) of 3D manipulation, symmetrically or asymmetrically between both hands. Author Keywords
Innovative Approaches for Designing and Analyzing Adaptive Dose-Ranging Trials

Inadequate selection of the dose to bring forward in confirmatory trials has been identified as one of the key drivers of the decreasing success rates observed in drug development programs across the pharmaceutical industry. In recognition of this problem, the Pharmaceutical Research and Manufacturers of America (PhRMA), formed a working group to evaluate and develop alternative approaches to dose finding, including adaptive dose-ranging designs. This paper summarizes the work of the group, including the results and conclusions of a comprehensive simulation study, and puts forward recommendations on how to improve dose ranging in clinical development, including, but not limited to, the use of adaptive dose-ranging methods.
Delayed neutrophil apoptosis enhances NET formation in cystic fibrosis

Background Cystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation. We hypothesised that the delay in apoptosis in CF is a primary defect and preferentially allows CF neutrophils to form NETs, contributing to inflammation. Methods Blood neutrophils were isolated from patients with CF, CF pigs and appropriate controls. Neutrophils were also obtained from patients with CF before and after commencing ivacaftor. Apoptosis was assessed by morphology and flow cytometry. NET formation was determined by fluorescent microscopy and DNA release assays. NET interaction with macrophages was examined by measuring cytokine generation with ELISA and qRT-PCR. Results CF neutrophils live longer due to decreased apoptosis. This was observed in both cystic fibrosis transmembrane conductance regulator (CFTR) null piglets and patients with CF, and furthermore was reversed by ivacaftor (CFTR potentiator) in patients with gating (G551D) mutations. CF neutrophils formed more NETs and this was reversed by cyclin-dependent kinase inhibitor exposure. NETs provided a proinflammatory stimulus to macrophages, which was enhanced in CF. Conclusions CF neutrophils have a prosurvival phenotype that is associated with an absence of CFTR function and allows increased NET production, which can in turn induce inflammation. Augmenting neutrophil apoptosis in CF may allow more appropriate neutrophil disposal, decreasing NET formation and thus inflammation.
Wolbachia mosquito control: Tested.

E. L. S. Loreto and G. L. Wallau (“Risks of Wolbachia mosquito control,” Letters, 18 March, p. [1273][1]) suggest that the risks associated with the Eliminate Dengue Program's release of Wolbachia -infected mosquitoes have been insufficiently assessed. In particular, they raise the possibility
Bayesian statistical analysis for spams

This paper presents a Bayesian statistical analysis applied to the spam problem. In most anti-spam related research, generally it is assumed that the probability of a spam occurrence is equal to 0.5, which is in our opinion unrealistic. It is also assumed that in the spam message, words are considered as an independent family of words. This makes us look at how the posterior probability behaves when the a priori probability is different from 0.5 and derive the consequences of the assumption of independent words on the posterior probability. The first assumption pushes us to define a prior and find a posterior probability laws to enhance the spam detection and increase the reliability decision. This analysis differs from previous results, that used the Bayesian approach to the anti-spam issue, especially through refinement and enhancement of various probability laws.
Relative performance of the two hands in simple and choice reaction time tasks

There is evidence that the left hemisphere is more competent for motor control than the right hemisphere. This study investigated whether this hemispheric asymmetry is expressed in the latency/duration of sequential responses performed by the left and/or right hands. Thirty-two right-handed young adults (16 males, 16 females; 18-25 years old) were tested in a simple or choice reaction time task. They responded to a left and/or right visual target by moving their left and/or right middle fingers between two keys on each side of the midline. Right hand reaction time did not differ from left hand reaction time. Submovement times were longer for the right hand than the left hand when the response was bilateral. Pause times were shorter for the right hand than the left hand, both when the responses were unilateral or bilateral. Reaction time results indicate that the putatively more efficient response preparation by the left hemisphere motor mechanisms is not expressed behaviorally. Submovement time and pause time results indicate that the putatively more efficient response execution by the left hemisphere motor mechanisms is expressed behaviorally. In the case of the submovements, the less efficient motor control of the left hand would be compensated by a more intense attention to this hand.
Longitudinal study of the influence of lung function on vascular health from adolescence to early adulthood in a British multiethnic cohort

Background: Vascular and lung function develop and decline over the life course; both predict cardiovascular events and mortality but little is known of how they develop over time. We analysed their relationship in a multiethnic cohort study to test whether lung function from early adolescence to young adulthood affected vascular indices. Methods: ‘DASH’ (http://dash.sphsu.mrc.ac.uk) included 6643 children aged 11–13 years in 2003; a representative 10% sample (n = 665) participated in a pilot follow-up in 2013. Psychosocial, anthropometric, blood pressure (BP), and lung function measures were collected in both surveys; aortic pulse wave velocity (PWV) and augmentation index (AIx) were measured at aged 21–23 years. Relationships between forced expiratory volume Z-scores in 1 s (zFEV1), after global initiative-ethnic adjustments and BP, PWV, and AIx were tested in linear regression and general estimating statistical models. Results: In total, 488 people with complete data were included. At 11–13 years, SBP was positively associated with zFEV1 (coefficient = 1.90, 95% confidence interval 1.11–2.68, P < 0.001); but not at 21–23 years. The 10-year increase in zFEV1 was associated with rise in SBP (1.38, 0.25–1.51, P < 0.05) in mixed effect models adjusted for age, sex, ethnicity, waist to height ratio, employment, reported racism, smoking, and alcohol use but DBP change was unrelated. In fully adjusted models, neither PWV nor central AIx were associated with zFEV1 at 11–13 years or 21–23 years (P > 0.05). Conclusion: Forced expiratory volume change is positively and independently associated with SBP change from adolescence to young adulthood, suggesting earlier lung function plays important roles in SBP development. Vascular indices were unrelated to lung function or its change.