Miracle-dz/UniFAR-FTUs huggingface dataset:
Red nucleus lesions abolish the biphasic respiratory response to isocapnic hypoxia in decerebrate young rabbits.

1. The respiratory response to isocapnic hypoxia (inspired O2 fraction (FI,O1), 0.1‐0.12) was measured in twelve vagotomized, paralysed, artificially ventilated young rabbits (aged 26.6 +/‐ 0.4 days), following pre‐collicular decerebration. Phrenic nerve efferent activity was used as an index of central respiratory output (RO). In hypoxia RO increased after 1‐2 min (phase 1) but decreased over the subsequent 3‐4 min to, or below, the pre‐hypoxic control level (phase 2). 2. We used electrical stimulation to target areas in the mesencephalon which inhibit RO. Profiles of the response to stimulation were determined in a grid of electrode penetrations made mediolaterally and rostrocaudally at the level of the superior colliculi, in normoxia. Histology confirmed that stimulation in the red nucleus (RN) inhibited RO profoundly. 3. Electrolytic lesions were made bilaterally in RN inhibitory sites or in adjacent areas. The respiratory response to isocapnic hypoxia was measured again post‐lesioning. 4. In six rabbits with bilateral lesions in the RN, phase 2 of the respiratory response was abolished and RO remained elevated throughout the hypoxic exposure. However, in six rabbits with unilateral lesions in the RN, or with bilateral lesions placed in areas outside the RN that did not inhibit RO on electrical stimulation, the respiratory response remained biphasic. 5. In both groups of animals, blood pressure increased during 1‐3 min of hypoxia before decreasing to pre‐hypoxic levels. This cardiovascular response remained biphasic irrespective of whether animals showed a biphasic respiratory response or a sustained increase in RO after lesioning. 6. We conclude that structures within the RN are crucial to the mechanism producing a fall in RO during isocapnic hypoxaemia in the neonate.
Enhancement of soil–geogrid interactions in direct shear mode using attached elements as anchors

Abstract Soil reinforcement employing geosynthetics is significantly influenced by interactions which are governed by friction and adhesion at interface. To enhance interactions at soil–geogrid interface under direct shear conditions, effects of attaching elements as anchors to reinforcement has been evaluated. A well and poorly graded sand, one geogrid type, anchors with three different size and clamping lengths of 2, 4 and 6 cm from shear surface were used. Samples were prepared with a relative density of 80% and tested dry under normal pressures of 12.5, 25 and 50 kPa using large direct shear test. Factors investigated included soil grading and particle size, anchor size and anchorage length together with normal pressures. Results shows by attachment of anchors to upper geogrid surface, shear resistance to failure is significantly enhanced with increase in normal pressure and anchor size. This is attributed to soil-anchor friction at interfaces, mobilisation of soil passive resistance in front of anchors and tensile strength of reinforcement. Non-uniform sand having larger and angular particles resulted in more effective interactions with geogrid and anchors at interfaces and resulted in greater resistance to shear failure under direct shear loading. Soil particle size and anchorage length were found to be less influential factors on soil–geogrid interactions.
Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men.

OBJECTIVE: To determine whether Helicobacter pylori, a chronic bacterial infection often acquired in childhood, is associated with increased risk of coronary heart disease and stroke later in life. DESIGN: Nested case-control study. SETTING: Prospective study of cardiovascular disease in men aged 40-59 years at entry (1978-1980) in 24 British towns. SUBJECTS: 135 cases of myocardial infarction and 137 cases of stroke occurring before December 1991; 136 controls were identified, frequency matched to cases by town and age group. METHODS: Serum samples stored at entry were analysed by an enzyme linked immunosorbent assay for the presence of H pylori specific IgG antibodies. RESULTS: 95 of the myocardial infarction cases (70%) and 93 (68%) of the stroke cases were seropositive for H pylori compared with 78 (57%) of the controls (odds ratio for myocardial infarction 1.77, 95% confidence interval (CI) 1.06 to 2.95, P = 0.03; odds ratio for stroke 1.57, 95% CI 0.95 to 2.60, P = 0.07). Helicobacter pylori infection was associated with manual social class, residence in Northern England or Scotland, cigarette smoking, higher systolic pressure and blood glucose, and a lower height-standardised forced expiratory volume in one second. Adjustment for these factors attenuated the relation between H pylori and myocardial infarction (odds ratio = 1.31, 95% CI 0.70 to 2.43, P = 0.40) and effectively abolished the relation with stroke (odds ratio = 0.96, 0.46 to 2.02, P = 0.92). The relation between helicobacter infection and fatal myocardial infarction was slightly stronger (odds ratio 2.41, 95% CI 1.13 to 5.12) but was also markedly attenuated after adjustment (1.56, 95% CI 0.68 to 3.61). CONCLUSION: In this prospective study the association between Helicobacter pylori infection and increased risk of myocardial infarction and stroke was substantially confounded by the relation between this infection, adult social class, and major cardiovascular risk factors.
Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles

Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons.
NGF Signals through TrkA to Increase Clathrin at the Plasma Membrane and Enhance Clathrin-Mediated Membrane Trafficking

Neurotrophin (NT) signals may be moved from axon terminals to neuron cell bodies via signaling endosomes—organelles in which NTs continue to be bound to their activated receptors. Suggesting that clathrin-coated membranes serve as one source of signaling endosomes, in earlier studies we showed that nerve growth factor (NGF) treatment increased clathrin at the plasma membrane and resulted in colocalization of clathrin with TrkA, the receptor tyrosine kinase for NGF. Strikingly, however, we also noted that most clathrin puncta at the surface of NGF-treated cells did not colocalize with TrkA, raising the possibility that NGF induces a general increase in clathrin-coated membrane formation. To explore this possibility further, we examined the distribution of clathrin in NGF- and BDNF-treated cells. NGF signaling in PC12 cells robustly redistributed the adaptor protein AP2 and the clathrin heavy chain (CHC) to surface membranes. Using confocal and epifluorescence microscopy, as well as biochemical assays, we showed the redistribution of clathrin to be attributable to the activation of TrkA. Significantly, NGF signaled through TrkA to induce an increase in clathrin-mediated membrane trafficking, as revealed in the increased endocytosis of transferrin. In that BDNF treatment increased AP2 and clathrin at the surface membranes of hippocampal neurons, these findings may represent a physiologically significant response to NTs. We conclude that NT signaling increases clathrin-coated membrane formation and clathrin-mediated membrane trafficking and speculate that this effect contributes to their trophic actions via the increased internalization of receptors and other proteins that are present in clathrin-coated membranes.
Striking Plasticity of CRISPR-Cas9 and Key Role of Non-target DNA, as Revealed by Molecular Simulations

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system recently emerged as a transformative genome-editing technology that is innovating basic bioscience and applied medicine and biotechnology. The endonuclease Cas9 associates with a guide RNA to match and cleave complementary sequences in double stranded DNA, forming an RNA:DNA hybrid and a displaced non-target DNA strand. Although extensive structural studies are ongoing, the conformational dynamics of Cas9 and its interplay with the nucleic acids during association and DNA cleavage are largely unclear. Here, by employing multi-microsecond time scale molecular dynamics, we reveal the conformational plasticity of Cas9 and identify key determinants that allow its large-scale conformational changes during nucleic acid binding and processing. We show how the “closure” of the protein, which accompanies nucleic acid binding, fundamentally relies on highly coupled and specific motions of the protein domains, collectively initiating the prominent conformational changes needed for nucleic acid association. We further reveal a key role of the non-target DNA during the process of activation of the nuclease HNH domain, showing how the nontarget DNA positioning triggers local conformational changes that favor the formation of a catalytically competent Cas9. Finally, a remarkable conformational plasticity is identified as an intrinsic property of the HNH domain, constituting a necessary element that allows for the HNH repositioning. These novel findings constitute a reference for future experimental studies aimed at a full characterization of the dynamic features of the CRISPR-Cas9 system, and—more importantly—call for novel structure engineering efforts that are of fundamental importance for the rational design of new genome-engineering applications.
Thinness in the era of obesity : trends in children and adolescents in The Netherlands since 1980

European Journal of Public Health, Vol. 25, No. 2, 268–273 The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved. doi:10.1093/eurpub/cku130 Advance Access published on 14 August 2014 . Thinness in the era of obesity: trends in children and adolescents in The Netherlands since 1980
The role of perinatal problems in risk of co-morbid psychiatric and medical disorders in adulthood

ABSTRACT Background Perinatal problems may be associated with an increased risk for psychological and physical health problems in adulthood, although it is unclear which perinatal problems (low birthweight, preterm birth, low Apgar scores, and small head circumference), or what clusters of problems, are more likely to be associated with later health problems. It is also not known whether perinatal problems (singly or together) are associated with co-morbidity between psychological and physical health problems. Method A regional random sample (from Baltimore) of mothers and their children (n=1525) was followed from birth to adulthood (mean age 29 years). Perinatal conditions were measured at delivery. Psychological problems (depression and suicidal ideation) were measured with the General Health Questionnaire-28 (GHQ-28) and physical problems (asthma and hypertension) with the RAND-36 Health Status Inventory. Results Children with perinatal problems were generally at increased risk for depression, suicidal ideation and hypertension, and co-morbid depression and hypertension even after controlling for confounders. One possible underlying condition, preterm low birthweight (LBW), extracted by cluster analysis, considering all of the four perinatal problems, was associated with increased risk for psychological and physical health outcomes as well as co-morbidity of the two. Conclusions LBW, preterm birth and small head circumference singly increased the risk for both psychological and physical health problems, as well as co-morbid depression and hypertension, while low Apgar scores were only associated with psychological problems. Delineating different etiological processes, such as preterm LBW, considering various perinatal problems simultaneously, might be of benefit to understanding the fetal origin of adult illness and co-morbidity.
Rates of Asymptotic Regularity for Halpern Iterations of Nonexpansive Mappings

In this paper we obtain new effective results on the Halpern iterations of nonexpansive mappings using methods from mathematical logic or, more specifically, proof-theoretic techniques. We give effective rates of asymptotic regularity for the Halpern iterations of nonexpansive self-mappings of nonempty convex sets in normed spaces. The paper presents another case study in the project of {\em proof mining}, which is concerned with the extraction of effective uniform bounds from (prima-facie) ineffective proofs.
Natural vibration analysis of steel–concrete composite box beam using improved finite beam element method

Based on Hamilton’s principle and a cubic Hermite polynomial shape function, first the improved steel–concrete composite box beam element stiffness and mass matrixes with a few numbers of degree were derived by considering many influencing factors such as interface slip, shear lag, shear deformation, and rotational inertia, and then the finite beam element method program was established. The natural vibration frequencies of many steel–concrete composite box beam calculation samples with different spans, degrees of shear connection, and boundary conditions were calculated. The analysis results show that the finite beam element method calculation results are consistent with ANSYS’ calculation, thus demonstrating the rationality and validity of the improved steel–concrete composite box beam element stiffness and mass matrixes proposed in this study. Moreover, some meaningful conclusions to engineering design were drawn as follows: The effect of shear lag increases with the order of steel–concrete composite box beam’s natural vibration frequency and degree of shear connection. Shear deformation also increases with the order of steel–concrete composite box beam’s natural vibration frequency; thus, the shear deformation corresponding to the steel–concrete composite box beam’s high-order natural vibration frequency cannot be ignored. The interface slip of steel–concrete composite box beam’s high-order natural vibration frequency is negligible; however, the interface slip of steel–concrete composite box beam’s low-order natural vibration frequency cannot be ignored.
Group SCAD regression analysis for microarray time course gene expression data

MOTIVATION Since many important biological systems or processes are dynamic systems, it is important to study the gene expression patterns over time in a genomic scale in order to capture the dynamic behavior of gene expression. Microarray technologies have made it possible to measure the gene expression levels of essentially all the genes during a given biological process. In order to determine the transcriptional factors (TFs) involved in gene regulation during a given biological process, we propose to develop a functional response model with varying coefficients in order to model the transcriptional effects on gene expression levels and to develop a group smoothly clipped absolute deviation (SCAD) regression procedure for selecting the TFs with varying coefficients that are involved in gene regulation during a biological process. RESULTS Simulation studies indicated that such a procedure is quite effective in selecting the relevant variables with time-varying coefficients and in estimating the coefficients. Application to the yeast cell cycle microarray time course gene expression data set identified 19 of the 21 known TFs related to the cell cycle process. In addition, we have identified another 52 TFs that also have periodic transcriptional effects on gene expression during the cell cycle process. Compared to simple linear regression (SLR) analysis at each time point, our procedure identified more known cell cycle related TFs. CONCLUSIONS The proposed group SCAD regression procedure is very effective for identifying variables with time-varying coefficients, in particular, for identifying the TFs that are related to gene expression over time. By identifying the TFs that are related to gene expression variations over time, the procedure can potentially provide more insight into the gene regulatory networks.
Brief report: cautions against using the Stanford-Binet-IV to classify high-risk preschoolers.

OBJECTIVE To explore concurrent and predictive validity of the Stanford-Binet: Fourth Edition (SB-IV) by comparing scores on the SB-IV with scores from the Battelle Developmental Inventory (BDI) and later achievement scores in preschoolers at risk due to very low birthweight, and/or intraventricular hemorrhage (IVH) and other medical complications. METHODS At ages 3,4, and 5, 92 preschoolers were tested with the SB-IV and BDI as part of an 8-year early intervention follow-up. RESULTS The SB-IV and BDI concurrent correlations at ages 3, 4, and 5 were statistically significant (r = .73-.78, p < .0001), as were predictive correlations (r = .58-.85, p < .0001). However, the BDI and SB-IV failed to place the children in the same categories for intervention services. With the BDI as the comparison measure, SB-IV failed to detect 87% of the children who were "delayed" (by BDI) at age 3 and 50% of the "delayed" children at age 5. CONCLUSIONS Caution is recommended when using the SB-IV to assess high risk for early intervention eligibility.
Application of Information Theory for an Entropic Gradient of Ecological Sites

The present study was carried out to compute the straightforward formulations of information entropy for ecological sites and to arrange their locations along the ordination axes using the values of those entropic measures. The data of plant communities taken from six sites found in the Dedegul Mountain sub-district and the Sultan Mountain sub-district located in the Beysehir Watershed was examined in the present study. Firstly entropic measures (i.e., marginal entropy, joint entropy, conditional entropy and mutual entropy) were computed for each of the sites. Next principal component analysis (PCA) was applied to the data composed of the values of those entropic measures. As a result of the first axis of the applied PCA, the arrangement of the sites was found meaningful from an ecological point of view because the sites were located along with the first component axis of the PCA by illustrating the climatic differences between the sub-districts.
AGA Future Trends Committee report: Colorectal cancer: a qualitative review of emerging screening and diagnostic technologies.

Part 1. The AGA Future Trends Commitee–Charge and Process The AGA Future Trends Committee (FTC) was created in 2004 to further the AGA Strategic Plan by identifying and characterizing important trends in clinical practice and scientific-technological developments in the world in general, and medicine and gastroenterology in particular, that potentially will impact the AGA and/or its members in the coming 3‐5 years or beyond and to make strategic recommendations to the Governing Board on how AGA should deal with those trends and developments. These trends and developments may be economic, demographic, practice-based, scientific/technological, or political in nature.
Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology.
Complement‐mediated bactericidal activity of human milk to a serum‐susceptible strain of E. coli 0111

There has been a lot of controversy concerning the physiological significance of the complement system in human breast‐milk. This is mainly due to the observation that human milk contains predominantly non‐inflammatory and many anti‐inflammatory factors, while simultaneously protecting the infant against a wide range of infectious and other diseases. The present study was carried out to assess the contribution of the complement system to the bactericidal activity of the human colostrum and early lactational milk. Using a serum‐sensitive strain of Escherichia coli, different fractions of human breast‐milk were assessed for their ability to kill the bacteria, with and without inactivation of their complement components, in comparison to another strain of the bacteria species. Deposition of activated C3 fragments on the killed bacteria, using an established ELISA technique, was demonstrated, further proving that the human milk complement could be activated in vitro. The bactericidal activities of human milk were almost completely abolished by complement heat inactivation at 56 °C or by the addition of EDTA.