Miracle-dz/UniFAR-FTUs huggingface dataset:
'Might' Made Right

In recent work, MacFarlane [] and Egan et al. [] have used new observations about epistemic modals to motivate radical new semantic analyses. MacFarlane introduces a triple-indexed semantics which makes sentences with epistemic modals not just sensitive to the context of utterance and an index of evaluation but also to a context of assessment. Egan et al. propose that epistemically modalized sentences do not express standard propositions but functions from individuals to propositions, something like centered propositions. We will argue that these moves are not only problematic but also unnecessary.  The Standard Theory (Kratzer) () a. Every car must be inspected. b. In view of what the laws are, every car must be inspected. () a. That coin might have landed heads. b. In view of what the laws of physics provide, that coin might have landed heads. () a. Jackl might be the murderer. b. In view of what is known, Jackl might be the murderer. Kratzer’s picture [, , ]: • Modals are quantifiers over possible worlds. • Possibility modals are existential quantifiers, necessity modals are universal quantifiers. They are duals of each other. • Modals quantify over the worlds given by a background such as “in view of what the laws are” (i.e. the worlds compatible with what the laws are in the evaluation world). • The “ambiguity” between epistemic modals and deontic modals (and others) is really context-dependency.
Lipid binding and the scaffolding function of the Kinase Suppressor of Ras

The signal transduction field has recently seen a surge of interest in cascade scaffolding proteins. One of these, the Kinase Suppressor of Ras (KSR), has received a great deal of attention as a scaffold for the Ras/ERK signaling pathway. KSR interacts with both MEK and ERK, and possibly binds to Raf-1 as well. Very little is known about the regulation of KSR; however, it has been determined that membrane association is essential for its function in signal augmentation. KSR shares a high degree of sequence homology to Raf-1, including an almost identical phosphatidic acid binding region (PABR). Previous work in the Romero lab has determined the direct interaction of Raf-1 with phosphatidic acid is critical for its membrane recruitment. The PABR is a 35 amino acid sequence consisting of a poly-basic motif (PBM) flanked by two hydrophobic regions. Neutralization of the two arginine residues in the PBM abrogates the binding of Raf-1 to phosphatidic acid (PA), and consequently disrupts its membrane association. This thesis examines lipid-binding properties of the PABR and their potential role in the traffic and function of KSR. Using peptides corresponding to the PABR and tryptophan fluorescence spectroscopy, the data presented in the first section demonstrate that PA induces a blue-shift in the tryptophan emission spectra of WT KSR PABR, and this shift is specific for PA. The second section explores the cellular consequence of KSR PABR mutation. A KSR protein lacking the arginine residues in the PBM expressed in HIRcB fibroblasts retains its membrane-binding ability, but inhibits MEK and ERK phosphorylation in a dominant negative fashion. The data presented here support the conclusion that, although an intact PABR may not be essential for the membrane localization of KSR, it is essential for proper coupling of the pathway.
On Reduced-Complexity Equalization Based on Ungerboeck and Forney Observation Models

This correspondence investigates the asymptotic behavior of reduced-state intersymbol interference (ISI) equalizers, based on the Ungerboeck and Forney observation models. It is shown that Ungerboeck-based equalizers can suffer from correct-path-loss (CPL) even in the noiseless regime. ISI conditions that lead to CPL are analytically derived and illustrated by examples.
A nine‐test screening battery for athletes: a reliability study

Studies have shown that reduced neuromuscular control or strength increases the risk of acute injuries. It is hypothesized that a non‐functional movement pattern can predispose for injuries. In the present paper a detailed description of a test battery consisting of nine different tests to screen athletic movement pattern is provided. The aim was to evaluate the inter‐ and intra‐rater reliability of the test battery on a group of male elite soccer players. Twenty‐six healthy elite soccer players (17–28 years) were screened. Eighteen participated at a second occasion 7 days later. No significant difference (P=0.31) was found between test occasion 1 (LS means 18.3, 95% confidence interval 14.9–21.7) and test occasion 2 (18.0, 14.4–21.7) in the mean total score of the test battery. No significant difference in the inter‐rater reliability was found between the eight physiotherapists at the two test occasions. The intra‐class correlation coefficient was 0.80 and 0.81, respectively. The test battery showed good inter‐ and intra‐rater reliability. The screening battery is easy to use for familiarized professionals and requires minimal equipment. However, further studies are needed to confirm the validity of the test battery in injury prevention, rehabilitation and performance enhancement.
Challenges to the peer influence paradigm: results for 12–13 year olds from six European countries from the European Smoking Prevention Framework Approach study

Objective: To examine whether smoking onset in young adolescents is predicted by peer or parental smoking. Design: Longitudinal design with one pretest and one follow-up at 12 months. Setting: Schools in Finland, Denmark, the Netherlands, the United Kingdom, Spain and Portugal. Participants: 7102 randomly selected adolescents from six countries. Mean age was 12.78 years. Main outcome measures: Smoking behaviour of adolescents, peers and parents. Results: No support was found for peer smoking as an important predictor of smoking onset in most countries. Support was found for the selection paradigm, implying that adolescents choose friends with similar smoking behaviour. Support for the impact of parents on adolescent behaviour and the choice of friends was also found. Conclusions: Smoking uptake in this age cohort may be more strongly influenced by personal and parental influences than initially believed. Hence, social inoculation programmes teaching youngsters to resist the pressures to smoke may be less appropriate if youngsters have a positive attitude towards smoking, associate smoking with various advantages and look for peers with similar values. For this group attitudes towards smoking may thus guide future friend selection.
Developmental Patterns of Doublecortin Expression and White Matter Neuron Density in the Postnatal Primate Prefrontal Cortex and Schizophrenia

Postnatal neurogenesis occurs in the subventricular zone and dentate gyrus, and evidence suggests that new neurons may be present in additional regions of the mature primate brain, including the prefrontal cortex (PFC). Addition of new neurons to the PFC implies local generation of neurons or migration from areas such as the subventricular zone. We examined the putative contribution of new, migrating neurons to postnatal cortical development by determining the density of neurons in white matter subjacent to the cortex and measuring expression of doublecortin (DCX), a microtubule-associated protein involved in neuronal migration, in humans and rhesus macaques. We found a striking decline in DCX expression (human and macaque) and density of white matter neurons (humans) during infancy, consistent with the arrival of new neurons in the early postnatal cortex. Considering the expansion of the brain during this time, the decline in white matter neuron density does not necessarily indicate reduced total numbers of white matter neurons in early postnatal life. Furthermore, numerous cells in the white matter and deep grey matter were positive for the migration-associated glycoprotein polysialiated-neuronal cell adhesion molecule and GAD65/67, suggesting that immature migrating neurons in the adult may be GABAergic. We also examined DCX mRNA in the PFC of adult schizophrenia patients (n = 37) and matched controls (n = 37) and did not find any difference in DCX mRNA expression. However, we report a negative correlation between DCX mRNA expression and white matter neuron density in adult schizophrenia patients, in contrast to a positive correlation in human development where DCX mRNA and white matter neuron density are higher earlier in life. Accumulation of neurons in the white matter in schizophrenia would be congruent with a negative correlation between DCX mRNA and white matter neuron density and support the hypothesis of a migration deficit in schizophrenia.
Redox-controlled iron isotope fractionation during magmatic differentiation: an example from the Red Hill intrusion,

This study presents accurate and precise iron isotopic data for 16 co-magmatic rocks and 6 pyroxene- magnetite pairs from the classic, tholeiitic Red Hill sill in southern Tasmania. The intrusion exhibits a vertical con- tinuum of compositions created by in situ fractional crys- tallisation of a single injection of magma in a closed igneous system and, as such, constitutes a natural laboratory amenable to determining the causes of Fe isotope fraction- ation in magmatic rocks. Early fractionation of pyroxenes and plagioclase, under conditions closed to oxygen exchange, gives rise to an iron enrichment trend and an increase in fO2 of the melt relative to the Fayalite-Magnetite- Quartz (FMQ) buffer. Enrichment in Fe 3? /RFemelt is mir- rored by d 57 Fe, where VI Fe 2? -bearing pyroxenes partition 57 Fe-depleted iron, defining an equilibrium pyroxene-melt fractionation factor of D 57 Fepxmelt �� 0:25 & � 10 6 =T 2 . Upon magnetite saturation, the fO2 and d 57 Fe of the melt fall, commensurate with the sequestration of the oxidised, 57 Fe-enriched iron into magnetite, quantified as D 57 Femtnmelt ¼þ 0:20 & � 10 6 =T 2 . Pyroxene-magnetite pairs reveal an equilibrium fractionation factor of D 57 Femtnpx �þ 0:30 & at 900-1,000 C. Iron isotopes in differentiated magmas suggest that they may act as an indi- cator of their oxidation state and tectonic setting.
Circulating insulin inhibits glucagon secretion induced by arginine in type 1 diabetes.

OBJECTIVE To evaluate if insulin has a suppressive effect on the glucagon secretion stimulated by arginine in type 1 diabetes. RESEARCH DESIGN AND METHODS The alpha-cell response to an i.v. bolus of arginine (150mgkg(-1)) followed by an infusion of arginine (10mgkg(-1)min(-1)) was studied in random order during either low dose infusion (LDT) or high dose infusion (HDT) of insulin in ten patients with type 1 diabetes. The blood glucose level was clamped at an arterialized level of 5mmoll(-1) by a variable infusion of glucose. Venous C-peptide, glucagon, growth hormone, and insulin were analyzed. RESULTS The mean plasma concentration of insulin was four times higher during the HDT. The C-peptide level did not differ between the LDT and the HDT. During the LDT in response to arginine the blood glucose level increased from 5.0 to 5.8mmol l(-1) although the glucose infusion was markedly reduced, while no change was seen during the HDT. A significantly smaller increase in the glucagon levels during the HDT was seen (area under the curve of 413+/-45 vs 466+/-44pgml(-1)h(-1), P=0.03) while the growth hormone levels were almost identical. CONCLUSION This study demonstrates that a high level of circulating insulin exerts an inhibitory effect on the glucagon response to arginine in type 1 diabetes. Thus, the suppressive effect of insulin on the glucagon release from the alpha-cell seems to be general and not only dependent on stimulation by hypoglycemia.
USE OF LOW TIDAL VOLUME IN SEPTIC SHOCK MAY DECREASE SEVERITY OF SUBSEQUENT ACUTE LUNG INJURY

Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.4 ± 4.5 kg) underwent cecal ligation and perforation to induce sepsis. Sheep were then randomized to ventilation with low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory pressure of 10 cmH2O was applied in each case. Ringer’s lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Survival time was longer in the low- than in the high-tidal-volume group (21.8 ± 2.4 vs. 17.6 ± 4.1 h, respectively, P < 0.05). The times to develop hypotension and anuria were longer in the low-tidal-volume group (18.1 ± 3.1 vs. 12.0 ± 2.8 h, P < 0.05, and 17.6 ± 1.6 vs. 14.1 ± 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low- than in the high-tidal-volume group (P = 0.06), postmortem examination showed a lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group (7.1 ± 0.5 vs. 9.1 ± 0.7, P < 0.05). A low-tidal-volume ventilation strategy applied early during septic shock may be beneficial in terms of reducing the amount of lung edema and prolonging survival time.
Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005).

OBJECTIVE To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs. DESIGN Retrospective case-control study. ANIMALS 110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism. PROCEDURES Sensitivity and specificity of basal serum or plasma cortisol concentrations of either <or= 1 microg/dL or <or= 2 microg/dL to detect dogs with hypoadrenocorticism were estimated by use of the ACTH stimulation test as the gold standard. RESULTS Basal cortisol concentrations of <or= 1 microg/dL had excellent sensitivity (100%) and specificity (98.2%) for detecting dogs with hypoadrenocorticism. For basal cortisol concentrations of <or= 2 microg/dL, sensitivity was 100% but specificity was 78.2%. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of sensitivity and specificity, basal serum or plasma cortisol concentrations had high negative predictive values over a wide range of prevalence rates and can be used to rule out a diagnosis of hypoadrenocorticism. Dogs with basal cortisol concentrations > 2 microg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is <or= 2 microg/dL, little to no information regarding adrenal gland function can be obtained and an ACTH stimulation test should be performed.
Estimating risks from urban sewer flooding's -Combining quantitative microbial data with hydrological software to improve quantitative microbial risk assessment of urban sewer flooding's

: During heavy rain events diluted wastewater often flood streets and basements or occur as overflow. As a consequence, exposure to the water during cleaning basements may lead to infection or severe illness. The purpose of this study was to generate a new quantitative microbial risk assessment (QMRA) of the impacts of urban flooding on human health with less uncertainty on the pathogenic concentrations and the dilution factor. This was accomplished by firstly validating a hydraulic model by use of quantitative data from dry weather flow and combined sewer overflow (CSO) from sub-catchments of the model. Secondly, opportunistic sampling of flooding and CSO events showed elevated levels of ammonia and Enterococci spp. in flood water and CSO water when compared to stormwater and provided the basis for a risk assessment of flood water. By the approach of hydraulic modelling a risk of 4.9 x 10 -1 for single infections and 1.5 x 10 -2 for illness when exposed to Campylobacter in flooded basements (darkness) were estimated. By including the hydraulic model in the QMRA the uncertainty of the dilution factor for potential flood water was thereby reduced.
Interferon Signaling Is Dependent on Specific Tyrosines Located within the Intracellular Domain of IFNAR2c

Type I interferons (IFNs) are cytokines that play a central role in mediating antiviral, antiproliferative, and immunomodulatory activities in virtually all cells. These activities are entirely dependent on the interaction of IFNs with their particular cell surface receptor. In this report, we identify two specific tyrosine residues located within the cytoplasmic domain of IFNAR2c that are obligatory for IFN-dependent signaling. Various IFNAR2c tyrosine mutants were expressed in a human lung fibroscarcoma cell line lacking IFNAR2c (U5A). Stable clones expressing these mutants were analyzed for their ability to induce STAT1 and STAT2 activation, ISGF3 transcriptional complex formation, gene expression, and cell growth regulation in response to stimulation with type I IFNs. The replacement of all seven cytoplasmic tyrosine residues of IFNAR2c with phenylalanine resulted in a receptor unable to respond to IFN stimulation. Substitution of single tyrosines at amino acid residue 269, 316, 318, 337, or 512 with phenylalanine had no effect on IFN-dependent signaling, suggesting that no single tyrosine is essential for IFN receptor-mediated signaling. In addition, IFNAR2c retaining five proximal tyrosines residues (269, 306, 316, 318, and 337) or either two distal tyrosine residues (411 or 512) continued to be responsive to IFN stimulation. Surprisingly, the presence of only a single tyrosine at either position 337 or 512 was sufficient to restore a complete IFN response. These results indicate that IFN-dependent signaling proceeds through the redundant usage of two tyrosine residues in the cytoplasmic domain of IFNAR2c.
A Method to Culture GABAergic Interneurons Derived from the Medial Ganglionic Eminence

Understanding the mechanisms guiding interneuron development is a central aspect of the current research on cortical/hippocampal interneurons, which is highly relevant to brain function and pathology. In this methodological study we have addressed the setup of protocols for the reproducible culture of dissociated cells from murine medial ganglionic eminences (MGEs), to provide a culture system for the analysis of interneurons in vitro. This study includes the detailed protocols for the preparation of the dissociated cells, and for their culture on optimal substrates for cell migration or differentiation. These cultures enriched in interneurons may allow the investigation of the migratory behavior of interneuron precursors and their differentiation in vitro, up to the formation of morphologically identifiable GABAergic synapses. Live imaging of MGE–derived cells plated on proper substrates shows that they are useful to study the migratory behavior of the precursors, as well as the behavior of growth cones during the development of neurites. Most MGE-derived precursors develop into polarized GABAergic interneurons as determined by axonal, dendritic, and GABAergic markers. We present also a comparison of cells from WT and mutant mice as a proof of principle for the use of these cultures for the analysis of the migration and differentiation of GABAergic cells with different genetic backgrounds. The culture enriched in interneurons described here represents a useful experimental system to examine in a relatively easy and fast way the morpho-functional properties of these cells under physiological or pathological conditions, providing a powerful tool to complement the studies in vivo.
Heteroresistance to Itraconazole Alters the Morphology and Increases the Virulence of Cryptococcus gattii

ABSTRACT Cryptococcus gattii is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11 C. gattii strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of original cells and the level of heteroresistance to itraconazole (LHI) was observed in addition to a negative correlation between capsule size of heteroresistant clones and LHI. Moreover, heteroresistance to itraconazole increased the engulfment of C. gattii by macrophages and augmented fungal proliferation inside these cells, which probably accounted for the reduced survival of the mice infected with the heteroresistant clones and the higher fungal burden in lungs and brain. Our results indicate that heteroresistance to itraconazole is intrinsic and increases the virulence of C. gattii. This phenomenon may represent an additional mechanism that contributes to relapses of cryptococcosis in patients during itraconazole therapy.
Strain Variation in the Transcriptome of the Dengue Fever Vector, Aedes aegypti

Studies of transcriptome dynamics provide a basis for understanding functional elements of the genome and the complexity of gene regulation. The dengue vector mosquito, Aedes aegypti, exhibits great adaptability to diverse ecological conditions, is phenotypically polymorphic, and shows variation in vectorial capacity to arboviruses. Previous genome sequencing showed richness in repetitive DNA and transposable elements that can contribute to genome plasticity. Population genetic studies revealed a varying degree of worldwide genetic polymorphism. However, the extent of functional genetic polymorphism across strains is unknown. The transcriptomes of three Ae. aegypti strains, Chetumal (CTM), Rexville D-Puerto Rico (Rex-D) and Liverpool (LVP), were compared. CTM is more susceptible than Rex- D to infection by dengue virus serotype 2. A total of 4188 transcripts exhibit either no or small variation (<2-fold) among sugar-fed samples of the three strains and between sugar- and blood-fed samples within each strain, corresponding most likely to genes encoding products necessary for vital functions. Transcripts enriched in blood-fed mosquitoes encode proteins associated with catalytic activities, molecular transport, metabolism of lipids, carbohydrates and amino acids, and functions related to blood digestion and the progression of the gonotropic cycle. Significant qualitative and quantitative differences were found in individual transcripts among strains including differential representation of paralogous gene products. The majority of immunity-associated transcripts decreased in accumulation after a bloodmeal and the results are discussed in relation to the different susceptibility of CTM and Rex-D mosquitoes to DENV2 infection.