Miracle-dz/UniFAR-FTUs huggingface dataset:
Adverse effects of large tidal volume and low PEEP in canine acid aspiration.

When normal lungs are ventilated with large tidal volumes (VT) and end-inspired pressures (Pei), surfactant is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilatory with large VT-low PEEP would similarly increase edema following acute lung injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (HCl) induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 cm H2O) (large VT-low PEEP) and compared their results with dogs ventilated with a smaller VT (15 ml/kg) and 12 cm H2O PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnia in our preparation; the large VT was chosen to match Pei and end-inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) was kept at 8 mm Hg in both groups. Five hours after injury, the median lung wet weight to body weight ratio (WW/BW) was 25 g/kg higher in the large VT-low PEEP group than in the small VT-high PEEP group (p less than 0.05). Venous admixture (Qva/Qt) was similarly greater in the large VT-low PEEP group (49.8 versus 23.5%) (p less than 0.05). We conclude that small VT-high PEEP is a better mode of ventilating acute lung injury than large VT-low PEEP because edema accumulation is less and venous admixture is less. These advantages did not result from differences in Pei, end-inspiratory lung volume, or preload (Ppwtm). (ABSTRACT TRUNCATED AT 250 WORDS)
Glucotoxicity inhibits cAMP–protein kinase A‐potentiated glucose‐stimulated insulin secretion in pancreatic β‐cells葡萄糖毒性抑制cAMP‐PKA通路促进的胰岛β细胞中血糖刺激的胰岛素分泌

The effect of incretin is markedly blunted in patients with type 2 diabetes (T2D), and this reduced effect of incretin is correlated with a diminished insulintropic potency of glucagon‐like peptide‐1 (GLP‐1). We reported recently that GLP‐1 potentiates glucose‐stimulated insulin secretion (GSIS) mainly via activation of the cAMP–protein kinase A (PKA) signaling pathway in INS‐1E cells under hyperglycemic conditions. In the present study, we further explored whether glucotoxicity impairs cAMP–PKA‐mediated effects and its relevance to the reduced insulinotropic action of GLP‐1 in hyperglycemia.
Cardiovascular follow-up at school age after perinatal glucocorticoid exposure in prematurely born children: perinatal glucocorticoid therapy and cardiovascular follow-up.

OBJECTIVE To study whether antenatal or neonatal glucocorticoid therapy to reduce the incidence and severity of chronic lung disease in preterm infants is associated with long-term adverse cardiac effects and hypertension. DESIGN Retrospective matched-cohort study. SETTING Outpatient clinic of a tertiary care hospital. PARTICIPANTS One hundred ninety-three children aged 7 to 10 years who had been born prematurely between December 2, 1993, and September 15, 1997. Main Exposure Neonatal treatment with dexamethasone disodium phosphate(n = 48) or the clinically equally effective glucocorticoid hydrocortisone (n = 51), or only antenatal treatment with betamethasone disodium phosphate and betamethasone acetate (n = 51). These 3 groups were compared with a reference group of prematurely born children who had not been exposed to perinatal glucocorticoid therapy (n = 43). MAIN OUTCOME MEASURES General hemodynamic data (heart rate and blood pressure), cardiovascular function as assessed at echocardiography, intima-media thickness of the carotid arteries, and cardiac biochemical features as early markers of expansion and volume overload of the cardiac left ventricle (B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide). RESULTS No significant group differences were found for heart rate, blood pressure, biochemical features, intima-media thickness, or systolic or diastolic left ventricular function. CONCLUSIONS Although no differences were found in blood pressure and cardiovascular function at school age in children antenatally or neonatally treated with glucocorticoids, further cardiovascular follow-up may be advisable because cardiovascular dysfunction may become apparent only later in life.
Bone's mechanostat: a 2003 update.

The still-evolving mechanostat hypothesis for bones inserts tissue-level realities into the former knowledge gap between bone's organ-level and cell-level realities. It concerns load-bearing bones in postnatal free-living bony vertebrates, physiologic bone loading, and how bones adapt their strength to the mechanical loads on them. Voluntary mechanical usage determines most of the postnatal strength of healthy bones in ways that minimize nontraumatic fractures and create a bone-strength safety factor. The mechanostat hypothesis predicts 32 things that occur, including the gross anatomical bone abnormalities in osteogenesis imperfecta; it distinguishes postnatal situations from baseline conditions at birth; it distinguishes bones that carry typical voluntary loads from bones that have other chief functions; and it distinguishes traumatic from nontraumatic fractures. It provides functional definitions of mechanical bone competence, bone quality, osteopenias, and osteoporoses. It includes permissive hormonal and other effects on bones, a marrow mediator mechanism, some limitations of clinical densitometry, a cause of bone "mass" plateaus during treatment, an "adaptational lag" in some children, and some vibration effects on bones. The mechanostat hypothesis may have analogs in nonosseous skeletal organs as well.
Increased Dendritic Cell Numbers Impair Protective Immunity to Intracellular Bacteria Despite Augmenting Antigen-Specific CD8+ T Lymphocyte Responses1

Dendritic cells (DCs) reside in tissues, where they function as sentinels, providing an essential link between innate and adaptive immunity. Increasing the numbers of DCs in vivo augments T cell responses, and can cause dramatic CTL-dependent tumor regression. To determine whether greater DC numbers promoted T cell-mediated protection in the context of host defense against intracellular bacteria, we treated mice with Flt3 ligand (Flt3-L) to increase DCs in vivo and challenged them with Listeria monocytogenes. Unexpectedly, after primary challenge with Listeria, the overall control of Listeria infection was impaired in Flt3-L-treated mice, which had greater bacterial burden and mortality than controls. Similar results were obtained when DC numbers were increased by treatment with polyethylene glycol-conjugated GM-CSF rather than Flt3-L and in mice infected with Mycobacterium tuberculosis. Impaired protection was not due to dysfunctional T cell responses, as Flt3-L-treated mice had a greater frequency and absolute number of Ag-specific CD8+ T cells, which produced IFN-γ, exhibited cytolytic activity, and transferred protection. The increased Listeria burden in Flt3-L-treated mice was preferentially associated with DCs, which were unable to kill Listeria and more resistant to CTL lysis compared with macrophages in vitro. Although we cannot exclude the possibility that other potential effects, in addition to increased numbers of DCs, are shared by Flt3-L and polyethylene glycol-conjugated GM-CSF and contributed to the increase in susceptibility observed in treated mice, these results support the notion that DC numbers must be properly controlled within physiological limits to optimize host defense to intracellular bacterial pathogens.
Endemic occurrence of Mycobacterium kansasii in water-supply systems.

Of a total number of 1079 drinking water and colliery service water samples examined in an area of the North-Moravian Region Czechoslovakia, characterized by endemic occurrence of M. kansasii infections, 233 [21.6%] samples were found to be contaminated by mycobacteria, of these 20 [1.9%] by M. kansasii. Of additionally examined 510 water samples from the municipal water-supply network, which were collected in hospital laboratories and clinical departments as well as in the households of patients with M. kansasii infection and their possible contacts, 171 [33.5%] samples showed presence of mycobacteria, of these 18 [3.5%] were M. kansasii-positive. This mycobacterial species was isolated from the drinking water samples collected in two hospitals in the core of the endemic area, e.i. in the district of Karviná. In the district of Ostrava, where the drinking water supply, bot for colliery and households facilities, is provided from the same water-supply system, the presence of M. kansasii in the municipal water-supply network was not proved, but it was isolated from 5 samples of colliery drinking water. Further 114 samples taken from the local water treatment plant supplying the endemic area with drinking water were found to be free of M. kansasii species.
The EVH2 Domain of the Vasodilator-stimulated Phosphoprotein Mediates Tetramerization, F-actin Binding, and Actin Bundle Formation*

Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena/VASP family of proteins that are implicated in regulation of the actin cytoskeleton. All family members share a tripartite structural organization, comprising an N-terminal Ena/VASP homology (EVH) 1 domain, a more divergent proline-rich central part, and a common C-terminal EVH2 region of about 160–190 amino acids. Using chemical cross-linking, sucrose gradient sedimentation, and gel filtration analyses of different truncated VASP constructs, we demonstrate that the VASP EVH2 region is both necessary and sufficient for tetramerization. Moreover, co-sedimentation and fluorescent phalloidin staining showed that the EVH2 region binds and bundles F-actin in vitro and localizes to stress fibers in transfected cells. Analysis of the functional contribution of highly conserved blocks within this region indicated that residues 259–276 of human VASP are essential for the interaction with F-actin, whereas residues 343–380 are required for tetramerization, probably via coiled-coil formation. Interactions with F-actin are enhanced by VASP tetramerization. The results demonstrate that the C-terminal EVH2 segment is not only conserved in sequence but also forms a distinct functional entity. The data suggest that the EVH2 segment represents a novel oligomerization and F-actin binding domain.
HVDC flashover on the surface of conductive ice

For a generalized and systematic study of the flashover performance of iced insulators, we investigated the flashover characteristics of HVDC iced insulators on a physical model with different ice temperatures. Iced insulator was simulated by a frozen electrolyte channel connected to the low voltage electrode. HV electrode, made of tungsten, is at an adjustable distance above the electrolyte. Investigation was done in a small refrigerated chamber in which temperature can be obtained at any desired value between 20°C and −50°C. Results show that discharge characteristics do not change with temperature and the flashover voltage obtained with positive polarity is slightly higher than that obtained with negative polarity for high-resistivity liquids. Furthermore with relatively high resistivity liquids (r≥20 kΩcm−1) during icing period (decreasing temperature from 0° to −40°C) the ice resistance is higher than that measured during de-icing period (increasing temperature from −40°C to 0°C) therefore the minimum flashover voltage is lower in the latter case. At −40°C and below it is unlikely to have flashover on ice because ice resistivity is excessively large. Flashover voltage on ice covered with water film is always lower than that obtained with “dry” ice. In the case of uniform voltage stress of our experimental conditions the combination of both de-icing and water-film conditions of ice leads to worst possible situation.
Peroxisome proliferation in Arabidopsis

Peroxisomes are subcellular organelles with multiple functions mediated by their plasticity and dynamic behavior in plants. Changes in their shape, size, number and enzyme content occur in response to developmental and metabolic cues as well as environmental conditions. The number of peroxisomes per cell is thus mainly determined by its capacity to proliferate. In mammals, peroxisome proliferators such as the hypolipidemic drug clofibrate are perceived by the Peroxisome Proliferator-Activated Receptors (PPARs) nuclear receptors. Therein, activated transcription of the peroxisome biogenesis PEX11 genes and the recruitment of dynamin-related proteins lead to peroxisome proliferation. We recently reported that Arabidopsis thaliana, despite of lacking a PPAR homolog protein, activated the proliferation of peroxisomes in response to clofibrate. Concomitantly, clofibrate activated the expression of wound-responsive genes through the jasmonic acid signaling master regulator COI1 F-box protein. Besides, wounding activated the expression of the peroxisome biogenesis-related PEX1 and PEX14 genes, but not of PEX11 or DRP3A, which analogously to mammals, code for the main regulators of peroxisome proliferation in Arabidopsis. Thus, wounding did not activate peroxisome proliferation. Noteworthy, jasmonic acid-treated plants contained fewer but larger peroxisomes. Despite of the cross-talk between clofibrate- and wound-induced signaling, the proliferation of peroxisomes and the wound-activated defense remained uncoupled.
Sense of effort and other unpleasant sensations during exercise: clarifying concepts and mechanisms

Introduction The sense of effort is an essential component of all forms of exercise. Although extensively studied, exercise physiologists have failed to reach consensus about whether this sensation is based on afferent sensory feedback or is centrally generated and independent of such feedback. This confusion has led to misunderstandings regarding the neurological mechanisms responsible for the sense of effort as opposed to other specific sensations such as pain and temperature. Discussion A mechanism in which the sense of effort is centrally generated and independent of feedback had been proposed more than 150 years ago. However, a more recent concept of sense of effort as a subjective rating of exercise intensity based on various sensations experienced during exercise given by Borg may have caused confusion, especially among exercise physiologists. Many began to use and understand the sense of effort as a sensation that is generated by afferent sensory feedback. The information reviewed in this article, together with the examples given, constitutes a body of evidence in favour of a centrally generated sense of effort. Afferent sensory feedback is important for the conscious awareness of different sensations such as pain and temperature, and plays important roles in the control of homeostasis. However, peripheral sensory feedback does not seem to be important for the generation of the sense of effort. Conclusion The sense of effort and other specific sensations such as temperature, pain and other muscular sensations present two separate neurological mechanisms. While the former is centrally generated, the latter is based on afferent sensory feedback. An interaction of these sensations is likely the ultimate regulator of exercise performance. However, further investigation is required to fully understand these phenomena.
C5a delays apoptosis of human neutrophils by a phosphatidylinositol 3-kinase-signaling pathway.

BACKGROUND Studies have shown that survival factors including cytokines and growth factors delay apoptosis of human neutrophils via induction of the phosphatidylinositol-3 kinase (PI 3-K)/Akt pathway. In the present study, we explored whether complement fragment C5a has a modulatory effect on neutrophil apoptosis through this signaling pathway. METHODS Human neutrophils were isolated and treated with C5a for up to 24 hours, with or without wortmannin, a PI 3-K inhibitor, and staurosporine, a caspase-9 activator. Apoptosis was quantified by flow cytometry, using propidium iodide nuclear staining, and confirmed by the detection of DNA fragmentation on gel electrophoresis. PI 3-K downstream signaling events were evaluated by measuring the expression of cytosolic total and phosphorylated Akt and Bad proteins by Western blot analyses, and caspase-9 activity. RESULTS C5a inhibited neutrophil apoptosis in a dose- and time-dependent manner. The anti-apoptotic effects of C5a were markedly abrogated in the presence of wortmannin. Brief stimulation of neutrophils with C5a induced phosphorylation of Akt and Bad proteins through a PI 3-K-dependent pathway. Caspase-9 activity was minimal in C5a-treated cells, but markedly increased following PI 3-K inhibition by wortmannin. Finally, C5a reduced caspase-9 activity in staurosporine-treated cells. CONCLUSIONS This study demonstrates that C5a inhibits neutrophil apoptosis via a PI 3-K signaling pathway. This effect may be an important mechanism that improves cell survival and function in the inflammatory milieu.
Differential Recognition and Scavenging of Native and Truncated Macrophage-Derived Chemokine (Macrophage-Derived Chemokine/CC Chemokine Ligand 22) by the D6 Decoy Receptor1

The promiscuous D6 receptor binds several inflammatory CC chemokines and has been recently proposed to act as a chemokine-scavenging decoy receptor. The present study was designed to better characterize the spectrum of CC chemokines scavenged by D6, focusing in particular on CCR4 ligands and analyzing the influence of NH2-terminal processing on recognition by this promiscuous receptor. Using D6 transfectants, it was found that D6 efficiently bound and scavenged most inflammatory CC chemokines (CCR1 through CCR5 agonists). Homeostatic CC chemokines (CCR6 and CCR7 agonists) were not recognized by D6. The CCR4 agonists CC chemokine ligand 17 (CCL17) and CCL22 bound to D6 with high affinity. CCL17 and CCL22 have no agonistic activity for D6 (chemotaxis and calcium fluxes), but were rapidly scavenged, resulting in reduced chemotactic activity on CCR4 transfectants. CD26 mediates NH2 terminus processing of CCL22, leading to the production of CCL22 (3–69) and CCL22 (5–69) that do not interact with CCR4. These NH2-terminal truncated forms of CCL22 were not recognized by D6. The results presented in this study show that D6 recognizes and scavenges a wide spectrum of inflammatory CC chemokines, including the CCR4 agonists CCL22 and CCL17. However, this promiscuous receptor is not engaged by CD26-processed, inactive, CCL22 variants. By recognizing intact CCL22, but not its truncated variants, D6 expressed on lymphatic endothelial cells may regulate the traffic of CCR4-expressing cells, such as dendritic cells.
Fixed frequency series loaded resonant converter based battery charger which is insensitive to resonant component tolerances

This paper proposes an EV battery charger with a fixed frequency operated series loaded resonant converter(SRC). Due to the proposed fixed frequency operation the SRC is operated under ZCS turn on and turn off regardless of load condition, and the magnetic components and the EMI filters can be optimized. The proposed battery charger has minimum component count, which makes it possible to achieve low cost and high reliability. Also, it is insensitive to resonant component tolerances and therefore suitable for high volume manufacturing. Experimental results are provided from a 3.3kW prototype which was built for 2011 Future Energy Challenge Competition.
Substances released from probiotic Lactobacillus rhamnosus GR-1 potentiate NF-κB activity in Escherichia coli-stimulated urinary bladder cells.

Lactobacillus rhamnosus GR-1 is a probiotic bacterium used to maintain urogenital health. The putative mechanism for its probiotic effect is by modulating the host immunity. Urinary tract infections (UTI) are often caused by uropathogenic Escherichia coli that frequently evade or suppress immune responses in the bladder and can target pathways, including nuclear factor-kappaB (NF-κB). We evaluated the role of L. rhamnosus GR-1 on NF-κB activation in E. coli-stimulated bladder cells. Viable L. rhamnosus GR-1 was found to potentiate NF-κB activity in E. coli-stimulated T24 bladder cells, whereas heat-killed lactobacilli demonstrated a marginal increase in NF-κB activity. Surface components released by trypsin- or LiCl treatment, or the resultant heat-killed shaved lactobacilli, had no effect on NF-κB activity. Isolation of released products from L. rhamnosus GR-1 demonstrated that the induction of NF-κB activity was owing to released product(s) with a relatively large native size. Several putative immunomodulatory proteins were identified, namely GroEL, elongation factor Tu and NLP/P60. GroEL and elongation factor Tu have previously been shown to elicit immune responses from human cells. Isolating and using immune-augmenting substances produced by lactobacilli is a novel strategy for the prevention or treatment of UTI caused by immune-evading E. coli.
Les facteurs d'engagement à la marque : vers une approche intégrative

Avec l'emergence du paradigme cognitif et du paradigme relationnel, l'engagement s'est impose comme concept central de la fidelite. De nombreux travaux ont permis d'identifier les antecedents de l'engagement. Le rapprochement des differentes approches dans un cadre integrateur constitue un enjeu theorique. Notre contribution se situe a trois niveaux: 1. Nous montrons que les actes n'accroissent pas le pouvoir predictif des attitudes sur l'engagement lorsqu'ils resultent de l' etat psychologique interne de l'individu (par ex: «je lis regulierement ce magazine parce que je l'apprecie). Dans ce cas, un modele integrateur de l'approche attitudinale et de 1'approche comportementale ne semble pas presenter d'interet. Seuls les actes induits de maniere externe, au moyen de techniques telles que le pied dans la porte, l'amorcage ou le leurre, peuvent renforcer l'engagement a la marque. 2. Nous montrons que la multifidelite est un cas limite, a la frontiere du modele transactionneI et du modele relationnel de l'engagement (Garbarino et Johnson, 1999). Alors que la monofidelite est clairement associee dans la litterature a la forme « pure » de la fidelite relationnelle en raison de l'exclusivite de la relation, il existe une ambiguite sur le statut de la multifidelite, que nous contribuons a lever en degageant sa double dimension, transactionnelle et relationnelle. 3. Nous proposons et testons un modele integrant l'approche par l'implication et l'approche attitudinale de l'engagement. Nous montrons que le lien entre profil d'implication et engagement a la marque n'est pas direct, mais mediatise par la relation a la marque. L'influence de la valeur hedonique est decisive.
The anchorage function of CipA (CelL), a scaffolding protein of the Clostridium thermocellum cellulosome.

Enzymatic cellulose degradation is a heterogeneous reaction requiring binding of soluble cellulase molecules to the solid substrate. Based on our studies of the cellulase complex of Clostridium thermocellum (the cellulosome), we have previously proposed that such binding can be brought about by a special "anchorage subunit. " In this "anchor-enzyme" model, CipA (a major subunit of the cellulosome) enhances the activity of CelS (the most abundant catalytic subunit of the cellulosome) by anchoring it to the cellulose surface. We have subsequently reported that CelS contains a conserved duplicated sequence at its C terminus and that CipA contains nine repeated sequences with a cellulose binding domain (CBD) in between the second and third repeats. In this work, we reexamined the anchor-enzyme mechanism by using recombinant CelS (rCelS) and various CipA domains, CBD, R3 (the repeat next to CBD), and CBD/R3, expressed in Escherichia coli. As analyzed by non-denaturing gel electrophoresis, rCelS, through its conserved duplicated sequence, formed a stable complex with R3 or CBD/R3 but not with CBD. Although R3 or CBD alone did not affect the binding of rCelS to cellulose, such binding was dependent on CBD/R3, indicating the anchorage role of CBD/R3. Such anchorage apparently increased the rCelS activity toward crystalline cellulose. These results substantiate the proposed anchor-enzyme model and the expected roles of individual CipA domains and the conserved duplicated sequence of CelS.