Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of ERK and calcium in the hypoxia‐induced activation of HIF‐1

Oxygen‐dependent regulation of HIF‐1 activity occurs at multiple levels in vivo. The mechanisms regulating HIF‐1α protein expression have been most extensively analyzed but the ones modulating HIF‐1 transcriptional activity remain unclear. Changes in the phosphorylation and/or redox status of HIF‐1α certainly play a role. Here, we show that ionomycin could activate HIF‐1 transcriptional activity in a way that was additive to the effect of hypoxia without affecting HIF‐1α protein level. In addition, a calmodulin dominant negative mutant and W7, a calmodulin antagonist, as well as BAPTA, an intracellular calcium chelator, inhibited the hypoxia‐induced HIF‐1 activation. These results indicate that elevated calcium in hypoxia could participate in HIF‐1 activation. Furthermore, ERK but not JNK phosphorylation was evidenced in both conditions, ionomycin and hypoxia. PD98059, an inhibitor of the ERK pathway as well as a ERK1 dominant negative mutant also blocked HIF‐1 activation by hypoxia and by ionomycin. A MEKK1 (a kinase upstream of JNK) dominant negative mutant had no effect. In addition, BAPTA, calmidazolium, a calmodulin antagonist and PD98059 inhibited VEGF secretion by hypoxic HepG2. All together, these results suggest that calcium and calmodulin would act upstream of ERK in the hypoxia signal transduction pathway. © 2002 Wiley‐Liss, Inc.
Cumulative and after-effects of short and weak coordinated reset stimulation: a modeling study

We show that the dynamical multistability of a network of bursting subthalamic neurons, caused by synaptic plasticity has a strong impact on the stimulus-response properties when exposed to weak and short desynchronizing stimuli. Intriguingly, such stimuli can reliably shift the network from a stable state with pathological synchrony and connectivity to a stable desynchronized state with down-regulated connectivity. However, unlike in the case of stronger coordinated reset stimulation, after termination of weaker stimulation the network may undergo a transient rebound of synchrony. When the coordinated reset stimulation is even weaker and/or shorter, so that a single stimulation epoch is not effective, the network dynamics and connectivity can still be reshaped in a cumulative manner by repetitive stimulation delivery.
Lack of association of the MDR1 C3435T polymorphism with susceptibility to gastric cancer and peptic ulcer: a systemic review and meta-analysis.

BACKGROUND The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU). MATERIALS AND METHODS A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias. RESULTS Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them. CONCLUSIONS This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.
The Causal Set Approach to Quantum Gravity

The ideas of spacetime discreteness and causality are important in several of the popular approaches to quantum gravity. But if discreteness is accepted as an initial assumption, conflict with Lorentz invariance can be a consequence. The causal set is a discrete structure which avoids this problem and provides a possible history space on which to build a " path integral " type quantum gravity theory. Motivation, results and open problems are discussed and some comparisons to other approaches are made. Some recent progress on recovering locality in causal sets is recounted. On the occasion of his 60th birthday, this article is dedicated to Rafael Sorkin, without whom the causal set idea would not have survived its infancy. How can we reach a theory of quantum gravity? Many answers to this question have been proposed, motivated by different experiences and views of current theories [1]. A more specific set of questions might be: what demands should we put on our framework, so that it is best able to meet all the challenges involved in creating a theory of quantum gravity? What choices are most likely to give the correct theory, according to the clues we have from known physics? Are there any problems with our initial assumptions that may lead to trouble further down the road? The latter seems to be one of the most important strategic questions when beginning to formulate a candidate theory. For example, can a canonical approach overcome the multifaceted problem of time? And how far can a theory based on a fixed background spacetime be pushed? On the one hand, these questions may only be answered in the very attempt to formulate the theory. On the other, many such attempts have been made, and now that quantum gravity research has built up some history, perhaps it is time to plough some of the experience gained back into a new approach, laying the groundwork for our theory in such a way as to avoid well-known problems. The causal set program [2, 3, 4, 5, 6] represents such an attempt. In this review, some answers to the above questions, as embodied by the causal set program, are set out and explained, and some of their consequences are given. As part of this, the results and open problems in the program are discussed. In section 1, reasons for hypothesising spacetime discreteness are reviewed. The definition of a causal set …
A Comparison of Wrist Angular Kinematics and Forearm EMG Data for an Elite, Intermediate and Novice Standard Tennis Player Performing a One-handed Backhand Groundstroke

Wrist angular kinematics (flexion/extension) and electromyography (EMG) data of a one-handed tennis backhand groundstroke were compared for an elite, intermediate and novice standard tennis player. For this purpose, synchronisation of the data with respect to ball impact time was achieved by a system of wireless and wired triggers and receivers. All three players maintained wrist extension for the 0.6 second period centred on ball impact. The elite and intermediate player struck the ball with the wrist extended by an average of 10 o from neutral alignment whilst moving towards flexion. After ball impact the wrist moved back towards and further into extension. The novice player was characterised by fluctuations in the wrist flexion/extension angle prior to ball impact with the wrist extended on average by 30 o from neutral alignment at impact. The wrist of the novice palyer moved back towards and further into extension after ball impact, although less than for intermediate and elite players. For the elite player, peak EMG levels for the wrist flexors and extensors were reached consistently 0.050. 1 seconds prior to ball impact. Wrist flexor EMG levels for the intermediate and novice players peaked on average 0.02 seconds after ball impact and extensor EMG levels peaked at ball impact. For the novice player, both flexor and extensor EMG data exhibited fluctuations consistent with the wrist kinematics data. Previously cited conditions that predispose a novice player to injury were not observed in this study. Given current injury mechanism theories, the data from this study suggests that the susceptibility of a player to tennis elbow injury cannot be established by generic skill level alone. Tennis players need to analysed as individuals.
Use of Clinical Criteria and Molecular Diagnosis to More Effectively Monitor Patients Recovering after Severe Acute Respiratory Syndrome Coronavirus Infection

0.135 mg/L), with a maximum concentration 6 h after injection. These values are in the low range, compared with previously reported ranges [1, 3]. In those 2 reports, information concerning liver function and the concomitant drugs received are not available. These low concentrations are similar to the MICs of the Aspergillus species and can explain the slow evolution of the abscess. Three main explanations can be invoked for these low values. Pharmacokinetic interactions do not explain the low concentrations. With regard to the drugs the patient received, the interaction between tacrolimus and voriconazole leads to a higher concentration of tacrolimus and not to a lower concentration of voriconazole [4]. We did not find obvious interactions between voriconazole and prazosine, paroxetine, nicarpidine, or metopimazine. We can assess that the liver graft was not involved in these low concentrations of voriconazole, because it exhibited normal function. The sampling procedure can perhaps explain the low results. The CSF specimen was collected during 2 h through the intraventricular catheter. Therefore, the in vitro instability of voriconazole and/ or adsorption of voriconazole on the lines and collection materials of the intraventricular derivation are able to decrease measured CSF concentrations. Furthermore, we noticed in the previously reported data from Lutsar et al. [1] that, among samples that yielded the 7 lowest concentrations found (which were similar to ours), 4 samples were obtained through an intraventricular catheter. A nonhomogeneous distribution of voriconazole resulting from compression of the fourth ventricle could also explain the lower concentrations in ventricles, compared with the concentration expected from a lumbar puncture. In conclusion, voriconazole is highly active against Aspergillus species, but additional studies are needed to confirm that our low drug concentrations result from the method of sampling and not from poor efficacy of this molecule in the CSF.
Ultrasound Screening of Multifocal Atherosclerosis

Ultrasound Screening of Multifocal Atherosclerosis Aim. The aim of our study was to perform ultrasound screening of multifocal atherosclerosis (MFA), in patients with coronary atherosclerosis. Material and methods. Color duplex screening (CDS) and continuous wave (CW) doppler was used to study 32 clinically healthy persons and 87 patients with clinical data for ischemic heart disease (IHD). Results. We have found high frequency of MFA simultaneously affecting coronary, carotid and femoral arteries. Intima-media thickness (IMT), which is a coronary atherosclerosis marker, had verifiable increasing in the common carotid artery (CCA) and common femoral artery (CFA) in the case of patients with chronic heart disease (CHD). In patients with CHD using ultrasound we established high frequency of clinically non-manifested asymptomatic stenosis and thromboses of the internal carotid artery (ICA) and common femoral artery, as well as aneurysms of the abdominal aorta (AAA). Markers for CHD with high sensitivity were the atherosclerosis plaques of ICA and CFA as well as IMT of the CFA. The most sensitive and specific markers for CHD were the combination of the IMT and atherosclerosis plaques of CCA, ICA and CFA. Conclusion. Ultrasound diagnostic is the method of choice for simultaneous non-invasive screening of carotid, peripheral and MFA and has sensitive markers for coronary atherosclerosis.
Effect of obesity on retinal vascular structure in pre-adolescent children.

UNLABELLED OBJECTIVES. In adults, obesity is linked to changes in the retinal microvasculature. Limited research has been conducted into this association in children. We examined in a cohort of pre-adolescents the relationship between body mass index (BMI) and retinal vascular structure, including retinal vessel diameter and retinal vessel fractals, a measure of geometric patterns reflecting vessel density. METHODS A population-based study among school children (2 353/3 144 [75.3%], median age, 12.7 years) recruited from a random cluster sample of 21 schools was conducted during 2004-5. Retinal images were taken and vessel diameter and fractal dimension were quantified using computer-based programs following standardized protocols. Anthropometric measures (weight, height, waist circumference, and BMI) were obtained and defined using standardized protocols. RESULTS Children with the highest quartile of BMI had narrower retinal arteriolar diameter (2.8 μm narrower, p<0.0001) and wider venular caliber (4.2 μm wider, p=0.001) than those with BMI in the lowest quartile, after adjusting for age, sex, ethnicity, mean arterial blood pressure, iris color, axial length, birth weight and fellow retinal vessel caliber. Obese children had narrower retinal arteriolar diameter (2.8 μm narrower, p=0.01) and wider venular diameter (4.5 μm wider, p=0.01) than in non-overweight/obese children. Retinal fractal dimension was not significantly associated with BMI. Increasing quartiles of waist circumference were also associated with retinal vessel diameter. CONCLUSIONS Our data provide evidence of adverse retinal microvascular caliber changes in obese pre-adolescent children, well before the onset of metabolic and cardiovascular disease in adulthood, and support an early, generalized adverse effect of adiposity on microvascular structure.
Autographa californica Multicapsid Nucleopolyhedrovirus Efficiently Infects Sf9 Cells and Transduces Mammalian Cells via Direct Fusion with the Plasma Membrane at Low pH

ABSTRACT The budded virus (BV) of the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) infects insect cells and transduces mammalian cells mainly through the endocytosis pathway. However, this study revealed that the treatment of the virus bound to Sf9 cells at low pH could efficiently rescue the infectivity of AcMNPV in the presence of endocytosis pathway inhibitors. A colocalization assay of the major capsid protein VP39 with the early endosome marker EEA1 showed that at low pH, AcMNPV entered Sf9 cells via an endosome-independent pathway. Using a fluorescent probe (R18), we showed that at low pH, the viral nucleocapsid entered Sf9 cells via direct fusion at the cell surface. By using the myosin-specific inhibitor 2,3-butanedione monoxime (BDM) and the microtubule inhibitor nocodazole, the low pH-triggered direct fusion was demonstrated to be dependent on myosin-like proteins and independent of microtubules. The reverse transcription-PCR of the IE1 gene as a marker for viral entry showed that the kinetics of AcMNPV in cells triggered by low pH was similar to that of the normal entry via endocytosis. The low pH-mediated infection assay and VP39 and EEA1 colocalization assay also demonstrated that AcMNPV could efficiently transduce mammalian cells via direct membrane fusion at the cell surface. More importantly, we found that a low-pH trigger could significantly improve the transduction efficiency of AcMNPV in mammalian cells, leading to the potential application of this method when using baculovirus as a vector for heterologous gene expression and for gene therapy.
Using Bone's Adaptation Ability to Lower the Incidence of Stress Fractures

In three prospective epidemiologic studies of the effect of pre-military-induction sport activities on the incidence of lower extremity stress fractures during infantry basic training, recruits who played ball sports (principally basketball) regularly for at least 2 years before basic training had a significantly lower incidence of stress fractures (13.2%, 16.7%, and 3.6% in the three studies, respectively) than recruits who did not play ball sports (28.9%, 27%, and 18.8%, respectively). Preinduction running was not related to the incidence of stress fracture. To assess the tibial strain environment during these sport activities, we made in vivo strain measurements on three male volunteers from the research team. Peak tibial compression and tension strain and strain rates during basketball reached levels 2 to 5.5 times higher than during walking and about 10% to 50% higher than during running. The high bone strain and strain rates that occurred in recruits while playing basketball in the years before military induction may have increased their bone stiffness, according to Wolff's Law. The stiffer bone could tolerate higher stresses better, resulting in lower strains for a given activity and a lower incidence of stress fractures during basic training.
First-episode psychosis is characterized by failure of deactivation but not by hypo- or hyperfrontality

Background It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia. Method Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined. Results The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not. Conclusions First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.
The Roles of Perceived Social Support, Coping, and Loneliness in Predicting Internet Addiction in Adolescents

The current research aims to examine the roles of perceived social support, coping, and loneliness when predicting the Internet addiction in adolescents. The research participants included 300 high school students, with an average age of 16.49 and SD=1.27, attending schools in a city in Southeastern Anatolian Region during 2015-2016 academic years. Participant adolescents included 180 females (60%) and 120 males (40%). Data collection was conducted through Short Form of Young’s Internet Addiction Test, Revised Form of Multi-Dimensional Perceived Social Support Scale, Coping Scale for Children and Youth, and the UCLA Loneliness Scale – Short-Form. Descriptive statistics, Pearson Correlation Coefficient, and Multiple Linear Regression Analysis were used to analyze the research data. Research findings showed that perceived social support from significant other support, loneliness, and cognitive avoidance and problem solving among coping strategies significantly predicted Internet addiction. Family support and friend support as sub-dimensions of perceived social support and assistance seeking and behavioral avoidance among coping strategies were not found to predict Internet addiction. Research findings were discussed based on the relevant literature, interpreted, and suggestions for researchers were put forward. Keywords : Internet addiction, perceived social support, coping strategies, loneliness, adolescents
Relationships among interleukin-6, tumor necrosis factor-α, adipokines, vitamin D, and chronic periodontitis.

BACKGROUND The aim of this study is to explore relationships among serum adipokines, vitamin D, and clinical and microbial parameters of chronic periodontitis before and after treatment. METHODS Weight, height, and smoking status were recorded for 56 patients with chronic periodontitis. Plaque, gingivitis, bleeding on probing, suppuration, probing depth, and clinical attachment level were measured at all teeth present. Subgingival biofilm samples from each tooth were analyzed for levels of 40 bacterial species using checkerboard DNA-DNA hybridization. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α, adiponectin, leptin, resistin, and vitamin D were measured at baseline. Sample collection was then performed in a subset of the population 6 months after therapy (n = 17). Serum samples were analyzed using enzyme-linked immunosorbent assay and immunoassays. Differences in clinical, microbial, and serum factors among groups were sought using the Mann-Whitney U test. Correlations among factors were evaluated using regression analysis. Effects of therapy were sought using the Wilcoxon signed rank test. RESULTS There were positive correlations between adiponectin/vitamin D and between IL-6/leptin, negative correlations between IL-6/vitamin D and leptin/vitamin D, but no associations between serum analytes and clinical or microbial parameters. Sex and body mass index were associated with levels of adipokines. Periodontal therapy improved clinical and microbiologic parameters but did not influence the levels of serum analytes. CONCLUSION Adipokines and IL-6 levels were affected by sex and body mass index. Serum analytes were not influenced by periodontal therapy.
Fuzzy Regression Models Using the Least-Squares Method Based on the Concept of Distance

Fuzzy regression models are developed to construct the relationship between explanatory variables and responses in a fuzzy environment. In order to increase the explanatory performance of the model, the least-squares method is applied to determine the numeric coefficients based on the concept of distance. Unlike most existing approaches, the numeric coefficients in the proposed model can have negative values. The proposed model minimizes total estimation error in terms of the sum of the average squared distance between the observed and estimated responses based on a few alpha-cuts. The proposed approach is not limited to triangular fuzzy numbers; it can be used to carry out a large number of fuzzy observations efficiently because the model is based on traditional statistical methods. Comparisons with existing methods show that based on the total estimation error using the mean squared error and Kim and Bishu's criterion, the explanatory performance of the proposed model is satisfactory.
Preventive and Therapeutic Strategies for Diabetic Foot Ulcers

The prevalence of diabetes in the United States has grown dramatically in recent years, rising from 5.5% in 1990 to 9.3% in 2010. Today it is estimated there are more than 29 million adults in the United States living with diabetes, and approximately 15% of those individuals will develop foot ulcers in their lifetime. Diabetic foot ulcers (DFUs) often lead to complications such as deep infection, abscess, and osteomyelitis. They precede 71% to 85% of lower extremity amputations. In addition to causing significant disability, the economic cost of diabetes-related lower limb conditions is staggering. The event-year direct medical costs for DFUs and lower extremity amputations approximate $2147 and $9041, respectively, whereas the total economic burden exceeds $31 200 per patient for lower limb amputation. The aim of this current concepts review is to summarize our current understanding of this systemic disease as it relates to the foot and ankle and to provide evidence-based recommendations (Table 1) regarding preventive and therapeutic management of diabetic foot ulcers based on analysis of recent literature published since the previous review in 2010. A summary of recommendations can be found in Table 2.