Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding learning within a commercial video game: A case study

There has been an increasing interest in the debate on the value and relevance using video games for learning. Some of the interest stems from frustration with current educational methods. However, some of this interest also stems from the observations of large numbers of children that play video games. This paper finds that children can learn basic construction skills from playing a video game called World of Goo. The study also employed novel eye-tracking technology to measure endogenous eye blinks and eye gaze fixations. Measures of both these indicators of cognitive processing further suggested that children in the study learned to play the two video games, World of Goo and Bad Piggies. Overall, the results of the study provide further support of the potential for children to learn by playing commercial video games.
Bacteriophage Resistance Mechanisms in the Fish Pathogen Flavobacterium psychrophilum: Linking Genomic Mutations to Changes in Bacterial Virulence Factors

ABSTRACT Flavobacterium psychrophilum is an important fish pathogen in salmonid aquaculture worldwide. Due to increased antibiotic resistance, pathogen control using bacteriophages has been explored as a possible alternative treatment. However, the effective use of bacteriophages in pathogen control requires overcoming the selection for phage resistance in the bacterial populations. Here, we analyzed resistance mechanisms in F. psychrophilum after phage exposure using whole-genome sequencing of the ancestral phage-sensitive strain 950106-1/1 and six phage-resistant isolates. The phage-resistant strains had all obtained unique insertions and/or deletions and point mutations distributed among intergenic and genic regions. Mutations in genes related to cell surface properties, gliding motility, and biosynthesis of lipopolysaccharides and cell wall were found. The observed links between phage resistance and the genetic modifications were supported by direct measurements of bacteriophage adsorption rates, biofilm formation, and secretion of extracellular enzymes, which were all impaired in the resistant strains, probably due to superficial structural changes. The clustered regularly interspaced short palindromic repeat (CRISPR) region was unaffected in the resistant isolates and thus did not play a role as a resistance mechanism for F. psychrophilum under the current conditions. All together, the results suggest that resistance in F. psychrophilum was driven by spontaneous mutations, which were associated with a number of derived effects on the physiological properties of the pathogen, including reduced virulence under in vitro conditions. Consequently, phage-driven physiological changes associated with resistance may have implications for the impact of the pathogen in aquaculture, and these effects of phage resistance on host properties are therefore important for the ongoing exploration of phage-based control of F. psychrophilum.
Variants in the toll-like receptor signaling pathway and clinical outcomes of malaria.

BACKGROUND Malaria is one of the most significant infectious diseases in the world and is responsible for a large proportion of infant deaths. Toll-like receptors (TLRs), key components of innate immunity, are central to countering infection. Variants in the TLR-signaling pathway are associated with susceptibility to infectious diseases. METHODS We genotyped single nucleotide polymorphisms (SNPs) of the genes associated with the TLR-signaling pathway in patients with mild malaria and individuals with asymptomatic Plasmodium infections by means of polymerase chain reaction. RESULTS Genotype distributions for the TLR-1 I602S differed significantly between patients with mild malaria and persons with asymptomatic infection. The TLR-1 602S allele was associated with an odds ratio (OR) of 2.2 (P= .003; P(corrected)= . 015) for malaria among patients with mild malaria due to any Plasmodium species and 2.1 (P= .015; P(corrected)= . 75) among patients with mild malaria due to Plasmodium falciparum only. The TLR-6 S249P SNP showed an excess of homozygotes for the TLR-6 249P allele in asymptomatic persons, compared with patients with mild malaria due to any Plasmodium species (OR 2.1; 95% confidence interval [CI], 1.1- 4.2; P= .01; P(corrected)= . 05), suggesting that the TLR-6 249S allele may be a risk factor for malaria (OR, 2.0; 95% CI, 1.1-3.7; P=0.01; P(corrected)= . 05). The TLR-9 -1486C allele showed a strong association with high parasitemia (P< .001). CONCLUSIONS Our findings indicate that the TLR-1 and TLR-6 variants are significantly associated with mild malaria, whereas the TLR-9-1486C/T variants are associated with high parasitemia. These discoveries may bring additional understanding to the pathogenesis of malaria.
The internet as a cultural forum: Implications for research

Twenty-five years ago, Horace Newcomb and Paul Hirsch proposed a model for studying television as a cultural forum, as the most common reference point for public issues and concerns, particularly in American society. Over the last decade, the internet has emerged as a new communicative infrastructure and cultural forum on a global scale. Revisiting and reworking Newcomb and Hirsch’s classic contribution, this article: first, advances a model of the internet as a distinctive kind of medium comprising different communicative genres — one-to-one, one-to-many as well as many-to-many communication; and, second, the article presents an empirical baseline study of their current prevalence. The findings suggest that while blogs, social network sites and other recent genres have attracted much public as well as scholarly attention, ordinary media users may still be more inclined to engage in good old-fashioned broadcasting and interpersonal interaction. Despite a constant temptation to commit prediction, future research is well advised to ask how old communicative practices relate to new media.
Potentially inappropriate medication use among institutionalized elderly individuals in southeastern Brazil

In recent decades, the elderly population in Brazil has grown rapidly, as has concern for the health of this population. Institutionalization in nursing homes has appeared as an alternative form of health care for frail elderly that live alone. The present study evaluated the pharmacotherapy and inappropriate drug prescriptions for institutionalized elderly patients living in long-term institutions in southeastern Brazil. This research was conducted at five institutions with a total sample of 151 individuals aged at least 60 years. Databases were used to identify drug interactions, defined daily dose and inappropriate prescriptions. The prevalence of drug intake among the elderly was 95.36%, and there were an average of 3.31 ± 1.80 drug prescriptions per individual. Based on Beers criteria, the prevalence of inappropriate prescriptions was 25.83%. In addition, 70.2% of prescriptions were prescribed at a higher dosage than the defined daily dose (ATC/WHO). Potential drug interactions were identified for 54.11% of prescriptions; 81.42% of these were of moderate severity. The main inappropriate drugs were prescribed for cardiovascular and nervous system problems. Institutionalized elderly individuals presented a high consumption and misuse of medications, requiring professional intervention to monitor prescriptions and improve the quality of service for this population.
miRNA-34c inhibits myoblasts proliferation by targeting YY1

ABSTRACT miRNAs are increasingly being implicated as key regulators of cell proliferation, apoptosis, and differentiation. miRNA-34c appears to play a crucial role in cancer pathogenesis wherein it exerts its effect as a tumor suppressor. However, the role of miR-34c in myoblast proliferation remains poorly understood. Here, we found that overexpression miR-34c inhibited myoblasts proliferation by reducing the protein and mRNA expression of cell cycle genes. In contrast, blocking the function of miR-34c promoted myoblasts proliferation and increased the protein and mRNA expression of cell cycle genes. Moreover, miR-34c directly targeted YY1 and inhibited its expression. Similar to overexpression miR-34c, knockdown of YY1 by siRNA suppressed myoblasts proliferation. Our study provides novel evidence for a role of miR-34c in inhibiting myoblasts proliferation by repressing YY1. Thus, miR-34c has the potential to be used to enhance skeletal muscle development and regeneration.
Nervous control of optokinetic responses in the crab Carcinus

The eyes of the crab Carcinus follow the movement of a horizontally rotating striped drum with a constantly increasing lag. The relative movement or slip speed is the stimulus for the eye, which with increasing stimulus increases its speed of response over a range of slip speeds from 0.001°/s to 10.0°/s. The gain in the forward control system, i. e. the ratio of eye speed to slip speed, can be as great as 15. The slowest effective slip speed is very low, about a sixth of the speed of the sun across the sky. Whether a seeing eye is allowed to move or not, it will drive the other eye if the latter sees no contrasting objects. An eye can also be driven in this way after section of its optic tract or after painting the cornea. When an eye which is free to move is exposed to a stationary striped field it suppresses the optokinetic response of the other eye, but if the eye exposed to the stationary contrasting field is clamped to the carapace, it no longer suppresses the optokinetic response of the contralateral eye; i. e. clamping the eye has here the same effect as blinding it. The control of the eye movement appears to be unaffected statically or dynamically by proprioceptors of the eye region. The initiation of the rapid flick back in the optokinetic response also takes no account of proprioceptors, but seems to occur when the efferent impulses to eye muscles reach a threshold frequency, which is only slightly modified by blinding one eye. The flick back is synchronized on the two sides. A different reflex, protective retraction, is a fast movement of the eye back into its socket, for which the minimum stimulus can be a touch to one sensory hair alone. During the rapid return phase of the optokinetic response, and during the retraction reflex, the efferent optokinetic impulses are suppressed, and, in addition, peripheral neuromuscular inhibition of tonic motor activity occurs when protective retraction over-rides the optokinetic response. On extending again after retraction, the blinded eye of a unilaterally blinded crab returns to the point in the optokinetic response where it left off. There are spontaneous eye movements which, although of less than one degree, are adequate to excite visual receptors in a stationary visual field. This is demonstrated by the decrease of the tremor when the visual field is changed from a blank one to a contrasting one. In addition, a small scanning movement of a few degrees is initiated when a contrasting object is introduced into the visual field. Therefore there is every reason to suppose that stationary contrasting objects can be perceived by spontaneous and by scanning movements. Similarities of the control system with that in mammals are the lack of a positional proprioceptive effect, coupled with the importance of the motor outflow as a controlling factor. Although there is eye tremor, as in mammals, the main control of eye movements in the crab is by the movement and not by position of a striped field relative to the eye.
Human CSF GABA Concentrations: Revised Dowd for Controls, but Not Decreased in Huntington's Chorea

Abstract: γ‐Aminobutyric acid (GABA) concentrations were measured in CSF specimens from two large groups of control subjects, one without neurological or psychiatric disease, and one with a variety of neurological disorders not known to involve altered GABAergic function in brain. CSF GABA was also measured in patients with Huntington's chorea and in patients with other choreiform disorders. GABA was measured in CSF by a modification of the ion exchange‐fluorometric method that featured use of a relatively large cation exchange column, and a markedly decreased quantity of sulfosalicylic acid for deproteinization of CSF. Mean GABA concentrations in CSF were 87 and 77 nmol/liter for neurologically normal and abnormal control subjects, 82 nmol/liter for the Huntington's chorea patients, and 105 nmol/liter for patients with other forms of chorea. The mean concentration of homocarnosine was not reduced in CSF of Huntington's chorea patients as compared with controls. Mean CSF GABA concentrations found in control subjects were less than half the lowest control means previously reported. These low values are attributable in part to a reduction in on‐column hydrolysis of conjugated forms of GABA in CSF, which can be produced by excessive sulfosalicylic acid, and in part to improved chromatographic resolution of GABA from other unknown o‐phthalaldehyde‐reactive compounds in CSF. Analysis of free GABA in CSF does not appear useful for diagnosis of suspected Huntington's chorea, nor as a possible predictive test for persons genetically at risk for Huntington's chorea.
Lower diet glycaemic index in African than South Asian men in Trinidad and Tobago

In Trinidad and Tobago (T&T), diabetes is over two times more common in South Asian (SA) than African (AF) men, with a smaller difference in women. In the USA, high diet glycaemic index (GI) was associated with increased risk of developing diabetes. In T&T, dietary intake data are unavailable. The objective of this study was to conduct a pilot survey of the dietary habits of 50 AF and 50 SA subjects in order to develop a valid nutrition survey instrument for use in T&T. We hypothesized that diet GI would be lower in AF than SA subjects. We collected 24 h dietary recalls from a sample of adults from T&T (26 AF and 33 SA women, and 17 AF and 25 SA men), excluding subjects of mixed or other ethnic backgrounds and those with diabetes or other chronic disorders. AF women were of similar age, but taller and heavier than SA women. There was no significant difference in diet between AF and SA women. AF men were taller than SA men, but of similar age (34 ± 2 years versus 33 ± 2 years) and body mass index (24.1 ± 0.8 kg/m2 versus 23.3 ± 0.9 kg/m2, respectively). Intakes of energy, fat, protein, carbohydrate and fibre, and diet glycaemic load did not differ significantly, but AF men had a lower diet GI than SA men (56 ± 1 versus 59 ± 1, P < 0.05). Although not conclusive, these results are consistent with previous data suggesting that diet GI may contribute to the development of type 2 diabetes. The data collected during this survey will be useful in developing a food frequency questionnaire for use in T&T to allow this hypothesis to be tested more rigorously in this population.
The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, type of mutation, and adjuvant treatment.

PURPOSE The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups. PATIENTS AND METHODS A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8. RESULTS TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were associated with lymphatic invasion in proximal tumors. In distal colon tumors, deletions causing loss of amino acids were associated with worse survival. In proximal colon tumors, mutations in exon 5 showed a trend toward statistical significance (P < .05) when overall survival was considered. Dukes' C tumors with wild-type TP53 and those with mutated TP53 (proximal tumors) showed significantly better prognosis when treated with adjuvant chemotherapy. CONCLUSION Analysis of TP53 mutations from a large cohort of CRC patients has identified tumor site, type of mutation, and adjuvant treatment as important factors in determining the prognostic significance of this genetic alteration.
The theoretical foundations of Chinese medicine : systems of correspondence

Although in the United States the scientific value of acupuncture is only now being clinically evaluated for the first time, needling is only one of a number of therapeutic disciplines which have proved effective in China for over two thousand years and which today provide common remedies for more than one quarter of the world's population. Why, asks Dr. Porkert, shouldn't medical men everywhere have access to the premises and results of this medical knowledge? In this book he presents a coherent and systematic account of Chinese theories--the system of correspondence that underlies all of Chinese medicine--using a new and precise Latin terminology (with English equivalents provided for most terms) that he devised over the past decade. The book is based directly and exclusively on Chinese sources, including recent Chinese secondary literature.Chapter 1 introduces the concepts that are the foundation of the system of correspondences--the polar combination yin-yang, which provides a basis for the analysis of all phenomena into complementary groups, and "wu-hsing, " which Dr. Porkert calls the "Five Evolutive Phases," and which are used to resolve cyclic processes into five temporally and qualitatively distinct parts. In Chapter 2 he takes up concepts which relate the body to the cosmos under the title "Phase Energetics" "(yun-ch'i);" these define meteorological, climatic, and immunological factors in health and disease. Chapters 3 and 4 focus on systems of concepts concerned with the body itself. The author has named these systems orbisiconography, sinarteriology, and foraminology. Orbisiconography "(tsang-hsiang), " the "imagery of functional orbs," describes the relationships of the functional systems within the body. It is not, as Dr. Porkert points out, analogous to but the opposite of Western comparative anatomy. Sinarteriology, the study of energetic conduits "(ching-luo), " and foraminology, the study of sensitive points "(shu-hsueh), " indicate the functional relationships manifested at the body's surface as well as within it. The book's systematic description of these disciplines involved in acupuncture is a powerful antidote to basic misconceptions prevalent in earlier Western writing on the subject.This is Volume III in the MIT East Asian Science series, edited by Nathan Sivin.
Activity-based probes for rhomboid proteases discovered in a mass spectrometry-based assay

Rhomboid proteases are evolutionary conserved intramembrane serine proteases. Because of their emerging role in many important biological pathways, rhomboids are potential drug targets. Unfortunately, few chemical tools are available for their study. Here, we describe a mass spectrometry-based assay to measure rhomboid substrate cleavage and inhibition. We have identified isocoumarin inhibitors and developed activity-based probes for rhomboid proteases. The probes can distinguish between active and inactive rhomboids due to covalent, reversible binding of the active-site serine and stable modification of a histidine residue. Finally, the structure of an isocoumarin-based inhibitor with Escherichia coli rhomboid GlpG uncovers an unusual mode of binding at the active site and suggests that the interactions between the 3-substituent on the isocoumarin inhibitor and hydrophobic residues on the protease reflect S′ subsite binding. Overall, these probes represent valuable tools for rhomboid study, and the structural insights may facilitate future inhibitor design.
Epileptogenic action of caffeine during anoxia in the neonatal rat hippocampus

Excessive maternal caffeine consumption can lead to fetal and neonatal pathology, but the underlying mechanisms have not been determined. Here, we report that low doses of caffeine generate seizures when applied in conjunction with brief anoxic episodes in the hippocampus of neonatal rats in vitro. In control conditions, brief (4–6 minutes) anoxic episodes reversibly depressed evoked synaptic responses and blocked the physiological pattern of network activity. In the presence of caffeine (50 μM), similar anoxic episodes generated ictal (29%) or interictal (33%) epileptiform activities often followed during reoxygenation by recurrent spontaneous seizure activity that persisted for several hours. These effects are likely mediated by a blockade of adenosine receptors by caffeine because (1) in control conditions, caffeine antagonized the inhibitory effect of selective A1 receptor agonist N6‐cyclopentyladenosine on excitatory synaptic responses, and (2) epileptogenic effects of caffeine were reproduced by selective A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine and theophylline. Our findings suggest that endogenous adenosine released during anoxia acting via A1 receptors prevents seizures in the neonatal hippocampus and that the antagonism of these receptors by caffeine leads to epileptogenesis. This study suggests concerns about the safety of caffeine in the fetus and newborn. Ann Neurol 1999;46:95–102
Effect of Clonidine on Cardiac Norepinephrine Spillover in Isolated Rat Heart

The purpose of this study is to determine the effect of clonidine on cardiac norepinephrine spillover utilizing an isolated rat heart preparation with attached cardiac sympathetic nerves. Following a 20-minute stabilization period, the sympathetic ganglion for each heart preparation was electrically stimulated with 10V and 2 Hz for 30 seconds (S1: 60 pulses). Heart rate, left ventricular developed pressure, and coronary perfusion pressure was allowed to return to baseline and the perfusate was randomly switched to Krebs buffer containing one of two treatments: placebo or clonidine (1 μM). After 10 minutes of treatment, the sympathetic ganglion was again electrically stimulated with 10V and 2 Hz for 30 seconds (S2: 60 pulses). The perfusate exiting the heart before, during, and after each electrical stimulation was collected for the determination of cardiac norepinephrine spillover. Clonidine administration significantly reduced cardiac norepinephrine spillover by approximately 50% (P < 0.05) and was associated with a 36% reduction in heart rate (P < 0.05). These findings provide evidence that clonidine can directly suppress NE spillover from cardiac sympathetic nerve terminals. Thus, suppression of cardiac NE by clonidine may be due to stimulation of presynaptic α2-adrenergic receptors or imidazoline subtype I receptors located on cardiac sympathetic nerve terminals. Results from our study demonstrate a reduction in cardiac NE spillover by clonidine and provide additional evidence that it can directly suppress peripheral sympathetic activity in that our results were obtained utilizing an isolated perfused heart preparation with attached cardiac sympathetic nerves devoid of any CNS input.