Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the function of Fc‐specific binding of IgM to P lasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting

Acquired protection from Plasmodium falciparum malaria takes years to develop, probably reflecting the ability of the parasites to evade immunity. A recent example of this is the binding of the Fc region of IgM to VAR2CSA‐type PfEMP1. This interferes with specific IgG recognition and phagocytosis of opsonized infected erythrocytes (IEs) without compromising the placental IE adhesion mediated by this PfEMP1 type. IgM also binds via Fc to several other PfEMP1 proteins, where it has been proposed to facilitate rosetting (binding of uninfected erythrocytes to a central IE). To further dissect the functional role of Fc‐mediated IgM binding to PfEMP1, we studied the PfEMP1 protein HB3VAR06, which mediates rosetting and binds IgM. Binding of IgM to this PfEMP1 involved the Fc domains Cμ3‐Cμ4 in IgM and the penultimate DBL domain (DBLζ2) at the C‐terminus of HB3VAR06. However, IgM binding did not inhibit specific IgG labelling of HB3VAR06 or shield IgG‐opsonized IEs from phagocytosis. Instead, IgM was required for rosetting, and each pentameric IgM molecule could bind two HB3VAR06 molecules. Together, our data indicate that the primary function of Fc‐mediated IgM binding in rosetting is not to shield IE from specific IgG recognition and phagocytosis as in VAR2CSA‐type PfEMP1. Rather, the function appears to be strengthening of IE–erythrocyte interactions. In conclusion, our study provides new evidence on the molecular details and functional significance of rosetting, a long‐recognized marker of parasites that cause severe P. falciparum malaria.
Distributed Checkpointing: Analysis and Benchmarks

This work proposes a metric for the analysis and benchmarking of checkpointing algorithms through simulation; the results obtained show that the metric is a good checkpoint overhead indicator. The metric is implemented by ChkSim, a simulator that has been used to compare 18 quasi-synchronous checkpointing algorithms. A survey of previous analyses of checkpointing shows our study to be the most comprehensive comparison carried out so far. Chk-Sim is easy to use and guarantees that the algorithms are fairly compared by subjecting all of them to exactly the same simulation events. The information summarized here can certainly be used to guide the construction of practical quasi-synchronous checkpoint-restart toolkits for modern clusters.
Comparative effectiveness of botulinum toxin versus non-surgical treatments for treating lateral epicondylitis: a systematic review and meta-analysis

Objectives: To explore the effectiveness of botulinum toxin compared with non-surgical treatments in patients with lateral epicondylitis. Methods: Data sources including PubMed, Scopus, Embase and Airity Library from the earliest record to February 2017 were searched. Study design, patients’ characteristics, dosage/brand of botulinum toxin, injection techniques, and measurements of pain and hand grip strength were retrieved. The standardized mean differences (SMDs) in pain relief and grip strength reduction were calculated at the following time points: 2-4, 8-12, and 16 weeks or more after injection. Results: Six randomized controlled trials (321 participants) comparing botulinum toxin with placebo or corticosteroid injections were included. Compared with placebo, botulinum toxin injection significantly reduced pain at all three time points (SMD, -0.729, 95% confidence interval [CI], -1.286 to -0.171; SMD, -0.446, 95% CI, -0.740 to -0.152; SMD, -0.543, 95% CI, -0.978 to -0.107, respectively). Botulinum toxin was less effective than corticosteroid at 2-4 weeks (SMD, 1.153; 95% CI, 0.568-1.737) and both treatments appeared similar in efficacy after 8 weeks. Different injection sites and dosage/brand did not affect effectiveness. Botulinum toxin decreased grip strength 2-4 weeks after injection, and high equivalent dose could extend its paralytic effects to 8-12 weeks. Conclusions: When treating lateral epicondylitis, botulinum toxin was superior to placebo and could last for 16 weeks. Corticosteroid and botulinum toxin injections were largely equivalent, except the corticosteroid injections were better at pain relief in the early stages and were associated with less weakness in grip in the first 12 weeks.
The Affinity of a Major Ca2+ Binding Site on GRP78 Is Differentially Enhanced by ADP and ATP*

GRP78 is a major protein regulated by the mammalian endoplasmic reticulum stress response, and up-regulation has been shown to be important in protecting cells from challenge with cytotoxic agents. GRP78 has ATPase activity, acts as a chaperone, and interacts specifically with other proteins, such as caspases, as part of a mechanism regulating apoptosis. GRP78 is also reported to have a possible role as a Ca2+ storage protein. In order to understand the potential biological effects of Ca2+ and ATP/ADP binding on the biology of GRP78, we have determined its ligand binding properties. We show here for the first time that GRP78 can bind Ca2+, ATP, and ADP, each with a 1:1 stoichiometry, and that the binding of cation and nucleotide is cooperative. These observations do not support the hypothesis that GRP78 is a dynamic Ca2+ storage protein. Furthermore, we demonstrate that whereas Mg2+ enhances GRP78 binding to ADP and ATP to the same extent, Ca2+ shows a differential enhancement. In the presence of Ca2+, the KD for ATP is lowered ∼11-fold, and the KD for ADP is lowered around 930-fold. The KD for Ca2+ is lowered ∼40-fold in the presence of ATP and around 880-fold with ADP. These findings may explain the biological requirement for a nucleotide exchange factor to remove ADP from GRP78. Taken together, our data suggest that the Ca2+-binding property of GRP78 may be part of a signal transduction pathway that modulates complex interactions between GRP78, ATP/ADP, secretory proteins, and caspases, and this ultimately has important consequences for cell viability.
Central Nervous System and Cardiac Effects From Long-Acting Amide Local Anesthetic Toxicity in the Intact Animal Model

With the development of the newer long-acting amide local anesthetics, ropivacaine and levobupivacaine, numerous animal studies of LA systemic toxicity have emerged. Because of the complex nature of the human response to LA intoxication, the task of designing and interpreting these animal studies of LA toxicity can be difficult. Accordingly, this report will review the selection of an animal model for the study of LA toxicity; examine the pertinent in vivo animal studies that compare the central nervous system toxicity, cardiovascular toxicity, and the ease of resuscitation of the single enantiomer local anesthetics to racemic bupivacaine; and extrapolate these findings to the clinical setting. Reg Anesth Pain Med 2003;28:3-11.
A model-based music recommendation system for individual users and implicit user groups

of a dissertation at the University of Miami. Dissertation supervised by Professor Mitsunori Ogihara No. of pages in text: (103) This dissertation introduces several problems on music recommendation. To make a high-qualified recommender, we evaluate feature importance for favorite song detection from two perspectives. The experiment results expose that collaborative filtering signal is the most important feature among the analyzed features. A classifier combination method is proposed to leverage several classifiers trained by different data sources to predict music genre. The complemented genre labels are used in a recommendation system for individual users on local device. The recommender takes freshness, time pattern, genre, publish year, and favor into account to make recommendations. The recommender outperforms the baseline on mostly favorite songs. We propose an adapted recommendation method to response user feedbacks and find out local optimizations to improve the recommendation quality. Furthermore, a probability-based method is proposed to make recommendations for implicit user groups by integrating individual opinions on music.
Night Myopia Studied with an Adaptive Optics Visual Analyzer

Purpose Eyes with distant objects in focus in daylight are thought to become myopic in dim light. This phenomenon, often called “night myopia” has been studied extensively for several decades. However, despite its general acceptance, its magnitude and causes are still controversial. A series of experiments were performed to understand night myopia in greater detail. Methods We used an adaptive optics instrument operating in invisible infrared light to elucidate the actual magnitude of night myopia and its main causes. The experimental setup allowed the manipulation of the eye's aberrations (and particularly spherical aberration) as well as the use of monochromatic and polychromatic stimuli. Eight subjects with normal vision monocularly determined their best focus position subjectively for a Maltese cross stimulus at different levels of luminance, from the baseline condition of 20 cd/m2 to the lowest luminance of 22×10−6 cd/m2. While subjects performed the focusing tasks, their eye's defocus and aberrations were continuously measured with the 1050-nm Hartmann-Shack sensor incorporated in the adaptive optics instrument. The experiment was repeated for a variety of controlled conditions incorporating specific aberrations of the eye and chromatic content of the stimuli. Results We found large inter-subject variability and an average of −0.8 D myopic shift for low light conditions. The main cause responsible for night myopia was the accommodation shift occurring at low light levels. Other factors, traditionally suggested to explain night myopia, such as chromatic and spherical aberrations, have a much smaller effect in this mechanism. Conclusions An adaptive optics visual analyzer was applied to study the phenomenon of night myopia. We found that the defocus shift occurring in dim light is mainly due to accommodation errors.
A Single Nucleotide Polymorphism in the Stromal Cell-Derived Factor 1 Gene Is Associated with Coronary Heart Disease in Chinese Patients

Coronary heart disease (CHD) is highly prevalent globally and a major cause of mortality. Genetic predisposition is a non-modifiable risk factor associated with CHD. Eighty-four Chinese patients with CHD and 253 healthy Chinese controls without CHD were recruited. Major clinical data were collected, and a single nucleotide polymorphism (SNP) in the stromal cell-derived factor 1 (SDF-1) gene at position 801 (G to A, rs1801157) in the 3'-untranslated region was identified. The correlation between rs1801157 genotypes and CHD was evaluated by a multivariate logistic regression analysis. The allele frequency in the CHD and control groups was in Hardy-Weinberg equilibrium (HWE) (p > 0.05). The frequency of the GG genotype in the CHD group (59.5%) was significantly higher than that in the control group (49.8%) (p = 0.036). A number of variables, including male sex, age, presence of hypertension, and the levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), uric acid, and total bilirubin, were associated with CHD in a primary univariate analysis. In a multivariable logistic regression analysis, the GG genotype (GG:AA, odds ratio (OR) = 2.31, 95% confidence interval (CI) = 1.21–5.23), male sex, advanced age (≥60 years), presence of hypertension, LDL-C level ≥ 3.33 mg/dL, HDL-C level < 1.03 mg/dL, and TG level ≥ 1.7 mg/dL were independent risk factors for CHD.
Modulation of uptake of organic cationic drugs in cultured human colon adenocarcinoma Caco‐2 cells by an ecto‐alkaline phosphatase activity

Alkaline phosphatase (ALP) refers to a group of nonspecific phosphomonoesterases located primarily in cell plasma membrane. It has been described in different cell lines that ecto‐ALP is directly or indirectly involved in the modulation of organic cation transport. We aimed to investigate, in Caco‐2 cells, a putative modulation of 1‐methyl‐4‐phenylpyridinium (MPP+) apical uptake by an ecto‐ALP activity. Ecto‐ALP activity and 3H‐MPP+ uptake were evaluated in intact Caco‐2 cells (human colon adenocarcinoma cell line), in the absence and presence of a series of drugs. The activity of membrane‐bound ecto‐ALP expressed on the apical surface of Caco‐2 cells was studied at physiological pH using p‐nitrophenylphosphate as substrate. The results showed that Caco‐2 cells express ALP activity, characterized by an ecto‐oriented active site functional at physiological pH. Genistein (250 µM), 3‐isobutyl‐1‐methylxanthine (1 mM), verapamil (100 µM), and ascorbic acid (1 mM) significantly increased ecto‐ALP activity and decreased 3H‐MPP+ apical transport in this cell line. Orthovanadate (100 µM) showed no effect on 3H‐MPP+ transport and on ecto‐ALP activity. On the other hand, okadaic acid (310 nM) and all trans‐retinoic acid (1 µM) significantly increased 3H‐MPP+ uptake and inhibited ecto‐ALP activity. There is a negative correlation between the effect of drugs upon ecto‐ALP activity and 3H‐MPP+ apical transport (r = −0.9; P = 0.0014). We suggest that apical uptake of organic cations in Caco‐2 cells is affected by phosphorylation/dephosphorylation mechanisms, and that ecto‐ALP activity may be involved in this process. J. Cell. Biochem. 87: 408–416, 2002. © 2002 Wiley‐Liss, Inc.
Revealing Nucleic Acid Mutations Using Förster Resonance Energy Transfer-Based Probes

Nucleic acid mutations are of tremendous importance in modern clinical work, biotechnology and in fundamental studies of nucleic acids. Therefore, rapid, cost-effective and reliable detection of mutations is an object of extensive research. Today, Förster resonance energy transfer (FRET) probes are among the most often used tools for the detection of nucleic acids and in particular, for the detection of mutations. However, multiple parameters must be taken into account in order to create efficient FRET probes that are sensitive to nucleic acid mutations. In this review; we focus on the design principles for such probes and available computational methods that allow for their rational design. Applications of advanced, rationally designed FRET probes range from new insights into cellular heterogeneity to gaining new knowledge of nucleic acid structures directly in living cells.
Grade Inflation: An Issue for Higher Education?.

Grade inflation impacts university credibility, student courses of study, choices of institution, and other areas. There has been an upward shift in grades without a corresponding upward shift in knowledge gained. Some of the most frequently mentioned causes of grade inflation are: O student evaluations of professors, O student teacher dynamics, O merit-based financial aid, and O student expectations. O Among the reasons for higher student grades on the part of professors are: O fear of student evaluations, O avoidance of bad relations with students, O below average teaching skills, O lack of experience, O a lack of clearly stated objectives, and O job security. While grades are not a perfect answer to assessing student performance in a course they are still the best answer we have for evaluating students. In order to evaluate students more accurately, universities must identify the problems in grading and grading practices. Once this is accomplished new practices can be designed and policies implemented.
Is Physical Abuse, Neglect, or a Combination of Both More Predictive of Delinquent Behavior in a High-Risk Population?

ABSTRACT This study explored early abuse type and severity in relation to delinquency utilizing an archival longitudinal data set. These data were collected every 2 years, starting at age 4, from the individuals, caregivers, and teachers. Mean differences tests were conducted to determine how delinquency scores varied by abuse type and severity. These analyses used Child Protective Services reports of the type and severity of abuse as independent measures and the behavior problem scale from the Child Behavior Checklist, Youth Self Report, and Teacher Report Form as independent measures. Follow-up analyses of variance and post-hoc tests were conducted as necessary to clarify the relationship between abuse and delinquency. Although results did not reach significance, a relatively small mean difference was discovered between severity types (more severe maltreatment history demonstrating higher levels of delinquency) for teacher ratings of delinquency.
Activation of Toll-Like Receptors and Inflammasome Complexes in the Diabetic Cardiomyopathy-Associated Inflammation

Diabetic cardiomyopathy is defined as a ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and hypertension. Hyperglycemia, hyperlipidemia, and insulin resistance are major inducers of the chronic low-grade inflammatory state that characterizes the diabetic heart. Cardiac Toll-like receptors and inflammasome complexes may be key inducers for inflammation probably through NF-κB activation and ROS overproduction. However, metabolic dysregulated factors such as peroxisome proliferator-activated receptors and sirtuins may serve as therapeutic targets to control this response by mitigating both Toll-like receptors and inflammasome signaling.
Catheter-Associated Nocardia higoensis Bacteremia in a Child with Acute Lymphocytic Leukemia

ABSTRACT A 23-month-old child with leukemia who was receiving chemotherapy developed fevers. Serial blood cultures from a central venous catheter and a peripheral venous site grew an organism identified by 16S rRNA gene sequencing and phenotypic analysis as Nocardia higoensis, an opportunistic organism isolated once previously from a pulmonary infection in Japan.
Parental Monitoring Affects the Relationship between Depressed Mood and Alcohol-Related Problems in Adolescents

Background Parental monitoring has been identified as a protective factor for adolescent drinking, whereas depressed mood, peer substance use, and peer tolerance of substance use have been identified as risk factors. The purpose of this study was to test the association between depressed mood and alcohol-related problems in adolescents, and to test whether parental monitoring and peer substance use/tolerance of use moderate the strength of this relationship. Methods Participants included 227 adolescents (Mage = 15.36; 51.5% female) recruited from a hospital emergency department and surrounding community who completed self-report assessments. Results Hierarchical linear regression analysis demonstrated that depressed mood was associated with more alcohol-related problems. A significant interaction between depressed mood and parental monitoring indicated a moderating effect, with high levels of depressed mood being associated with alcohol-related problems when parental monitoring was low; at low levels of depressed mood, parental monitoring was not related to alcohol-related problems. Conclusions This study highlights the protective role that parental monitoring may play in the association between depressed mood and alcohol-related problems and suggests that parenting practices, in addition to individual counseling, should be addressed in treatment of depressed adolescents who drink.
Library Abstraction for C / C + + Concurrency — extended version —

When constructing complex concurrent systems, abstraction is vital: programmers should be able to reason about concurrent libraries in terms of abstract specifications that hide the implementation details. Relaxed memory models present substantial challenges in this respect, as libraries need not provide sequentially consistent abstractions: to avoid unnecessary synchronisation, they may allow clients to observe relaxed memory effects, and library specifications must capture these. In this paper, we propose a criterion for sound library abstraction in the new C11 and C++11 memory model, generalising the standard sequentially consistent notion of linearizability. We prove that our criterion soundly captures all client-library interactions, both through call and return values, and through the subtle synchronisation effects arising from the memory model. To illustrate our approach, we verify implementations against specifications for the lock-free Treiber stack and a producer-consumer queue. Ours is the first approach to compositional reasoning for concurrent C11/C++11 programs.
Role of Autonomic Regulatory Mechanisms in Sinoatrial Conduction and Sinus Node Automaticity in Sick Sinus Syndrome

To assess the role of autonomic regulatory mechanisms on sinoatrial conduction and automaticity in patients with clinical evidence of sick sinus syndrome, electrophysiologic studies were conducted in 12 male patients, mean age 64 4 7 years. Heart rate, sinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined before and after autonomic blockade with atropine (0.04 mg/kg) and propranolol (0.2 mg/kg). The mean sinus cycle length was 1033 ± 208 msec (4 SD) before autonomic blockade and 1016 4 188 msec after autonomic blockade. The observed intrinsic heart rate (1HRo) after autonomic blockade was abnormal in nine of 12 patients. The mean corrected SNRT before autonomic blockade was 606.5: 432 msec and was abnormal (< 450 msec) in six of 12 patients (50%). After autonomic blockade the mean SNRT was 661.8 + 604.8 msec and was abnormal (> 450 msec) in eight of 12 (67%). Six of nine patients (66%) with an abnormal intrinsic observed HR had an abnormal SNRTc before autonomic blockade. After autonomic blockade, eight of these nine (88%) had an abnormal SNRTc. SACT was estimated by continuous pacing and by premature stimulation. The mean SACT estimated by continuous pacing before autonomic blockade was 190.3 ± 99.6 msec and decreased significantly after autonomic blockade (140.6 ± 53.4 msec, p < 0.05). The mean SACT estimated by premature stimulation before autonomic blockade was 218 ± 87.6 msec and decreased significantly after autonomic blockade (143.7 ± 49.9 msec, p < 0.01). The coefficient of correlation between the two methods was 0.8 before autonomic blockade and 0.85 after autonomic blockade. SACT was abnormally prolonged (> 206 msec) in five of 12 patients (41%) during control studies and in two of 12 patients (16%) after autonomic blockade. SAC by either method decreased in eight of 12 patients (67%) and increased in four of 12 patients (33%) after autonomic blockade. Changes in SACT after autonomic blockade could not be predicted from symptoms, electrocardiographic findings or determination of intrinsic HR. In conclusion, assessment of IHR, SNRT and SACT after autonomic blockade can differentiate patients with sick sinus syndrome, whether due to intrinsic or extrinsic abnormality of sinus node automaticity or conduction. The significant decrease in SACT in most patients with sick sinus syndrome after autonomic blockade suggests enhanced basal parasympathetic tone and normal intrinsic conduction in the perinodal region. The increase in SACT in a minority of patients after autonomic blockade suggests that enhanced basal sympathetic tone can mask an underlying intrinsic abnormality of sinoatrial conduction.