Recently, we showed that the self-field transport critical current, I
(sf), of a superconducting wire can be defined in a more fundamental way than the conventional (and arbitrary) electric field ...criterion, E
= 1 μV/cm. We defined I
(sf) as the threshold current, I
, at which the perpendicular component of the local magnetic flux density, B
, measured at any point on the surface of a high-temperature superconducting tape abruptly crosses over from a non-linear to a linear dependence with increasing transport current. This effect results from the current distribution across the tape width progressively transitioning from non-uniform to uniform. The completion of this progressive transition was found to be singular. It coincides with the first discernible onset of dissipation and immediately precedes the formation of a measureable electric field. Here, we show that the same I
definition of critical currents applies in the presence of an external applied magnetic field, B
. In all experimental data presented here I
is found to be significantly (10-30%) lower than I
determined by the common electric field criterion of E
= 1 µV/cm, and E
to be up to 50 times lower at I
than at I
.
Raman microspectroscopy was applied to monitor the intracellular redox state of myoglobin and cytochrome c from isolated adult rat cardiomyocytes during hypoxia and reoxygenation. The nitrite ...reductase activity of myoglobin leads to the production of nitric oxide in cells under hypoxic conditions, which is linked to the inhibition of mitochondrial respiration. In this work, the subsequent reoxygenation of cells after hypoxia is shown to lead to increased levels of oxygen-bound myoglobin relative to the initial levels observed under normoxic conditions. Increased levels of reduced cytochrome c in ex vivo cells are also observed during hypoxia and reoxygenation by Raman microspectroscopy. The cellular response to reoxygenation differed dramatically depending on the method used in the preceding step to create hypoxic conditions in the cell suspension, where a chemical agent, sodium dithionite, leads to reduction of cytochromes in addition to removal of dissolved oxygen, and bubbling-N2 gas leads to displacement of dissolved oxygen only. These results have an impact on the assessment of experimental simulations of hypoxia in cells. The spectroscopic technique employed in this work will be used in the future as an analytical method to monitor the effects of varying levels of oxygen and nutrients supplied to cardiomyocytes during either the preconditioning of cells or the reperfusion of ischaemic tissue.
The variation in transition temperature T c with oxygen deficiency or calcium substitution in Y 1-x Ca x Ba 2 Cu 3 O 7-δ (YBCO) is a well-known manifestation of the generic hole-doping phase diagram ...governing the superconducting cuprates. Less well understood is the role that microstructural defects can play in determining hole doping. We have investigated the formation of Y124-type stacking faults in metal-organic deposited (MOD) YBCO coated conductors and shown that these defects also act to reduce the hole concentration in YBCO. With low stacking-fault density, T c can be as low as 89 K when fully oxygen loaded and can increase to a maximum of 94 K when partially unloaded. The presence of stacking faults limits the degree to which fully oxygen loaded YBCO can be overdoped. The critical current density J c is optimized by full oxygen loading but with a moderate density of stacking faults. We have demonstrated substitution of calcium for yttrium in YBCO by modification of the MOD precursor resulting in an increase in hole concentration and consequent decrease in T c . J c is initially depressed by calcium substitution but partially recovers upon incorporation of a moderate density of stacking faults.
The loss of intracellular potassium is a pivotal step in the induction of apoptosis but the mechanisms underlying this response are poorly understood. Here we report caspase-dependent stimulation of ...potassium channels by the Fas receptor in a human Jurkat T cell line. Receptor activation with Fas ligand for 30 min increased the amplitude of voltage-activated potassium currents 2-fold on average. This produces a sustained outward current, ∼10 pA, at physiological membrane potentials during Fas ligand-induced apoptosis. Both basal and Fas ligand-induced currents were blocked completely by toxins that selectively inhibit Kv1.3 potassium channels. Kv1.3 stimulation required the expression of Fas-associated death domain protein and activation of caspase 8, but did not require activation of caspase 3 or protein synthesis. Furthermore, Kv1.3 stimulation by Fas ligand was prevented by chronic stimulation of protein kinase C with 20 nm phorbol 12-myristate 13-acetate during Fas ligand treatment, which also blocks apoptosis. Thus, Fas ligand increases Kv1.3 channel activity through the same canonical apoptotic signaling cascade that is required for potassium efflux, cell shrinkage, and apoptosis.
Trauma is the number one killer of individuals 1-44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, ...with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition.
We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40-80 h window post-injury.
The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions.
ClinicalTrials.gov NCT00257231
Fetal outcome in obstetric cholestasis Fisk, N M; Storey, G N
British journal of obstetrics and gynaecology,
November 1988, Letnik:
95, Številka:
11
Journal Article
Recenzirano
Obstetric cholestasis has been associated with a high incidence of stillbirth and perinatal complications. Between 1975 and 1984, 83 pregnancies were complicated by cholestasis. Meconium staining ...occurred in 45%, spontaneous preterm labour in 44%, and intrapartum fetal distress in 22%. Of 86 infants two were stillborn and one died soon after birth. Perinatal mortality fell from 107 in a previous series from this hospital (1965-1974) to 35/1000 in this series. Cardiotocography, estimations of oestriol, liver function tests and ultrasonic assessment of amniotic fluid volume failed to predict fetal compromise, whereas amniocentesis revealed meconium in 8 of 26 pregnancies. Early intervention was indicated in 49 pregnancies, 12 because of fetal compromise. This study suggests that intensive fetal surveillance, including amniocentesis for meconium, and induction of labour at term or with a mature lecithin/sphyngomyelin ratio, may reduce the stillbirth rate in this 'high-risk' condition.
Many nuclear hormones have physiological effects that are too rapid to be explained by changes in gene expression and are often attributed to unidentified or novel G protein-coupled receptors. ...Thyroid hormone is essential for normal human brain development, but the molecular mechanisms responsible for its effects remain to be identified. Here, we present direct molecular evidence for potassium channel stimulation in a rat pituitary cell line (GH₄C₁) by a nuclear receptor for thyroid hormone, TRβ, acting rapidly at the plasma membrane through phosphatidylinositol 3-kinase (PI3K) to slow the deactivation of KCNH2 channels already in the membrane. Signaling was disrupted by heterologous expression of TRβ receptors with mutations in the ligand-binding domain that are associated with neurological disorders in humans, but not by mutations that disrupt DNA binding. More importantly, PI3K-dependent signaling was reconstituted in cell-free patches of membrane from CHO cells by heterologous expression of human KCNH2 channels and TRβ, but not TRα, receptors. TRβ signaling through PI3K provides a molecular explanation for the essential role of thyroid hormone in human brain development and adult lipid metabolism.
We present the initial results of a 3-mm spectral-line survey towards 83 methanol maser-selected massive star-forming regions. Here, we report observations of the J = 5–4 and 6–5 rotational ...transitions of methyl cyanide (CH3CN) and the J = 1–0 transition of HCO+ and H13CO+. CH3CN emission is detected in 58 sources (70 per cent of our sample). We estimate the temperature and column density for 37 of these using the rotational diagram (RD) method. The temperatures we derive range from 28–166 K, and are lower than previously reported temperatures, derived from higher J transitions. We find that CH3CN is brighter and more commonly detected towards ultracompact H ii (UCH ii) regions than towards isolated maser sources. Detection of CH3CN towards isolated maser sources strongly suggests that these objects are internally heated and that CH3CN is excited prior to the UCH ii phase of massive star formation. HCO+ is detected towards 82 sources (99 per cent of our sample), many of which exhibit asymmetric line profiles compared to H13CO+. Skewed profiles are indicative of inward or outward motions, however, we find approximately equal numbers of red- and blue-skewed profiles among all classes. Column densities are derived from an analysis of the HCO+ and H13CO+ line profiles. 80 sources have mid-infrared (mid-IR) counterparts: 68 seen in emission and 12 seen in absorption as ‘dark clouds’. Seven of the 12 dark clouds exhibit asymmetric HCO+ profiles, six of which are skewed to the blue, indicating infalling motions. CH3CN is also common in dark clouds, where it has a 90 per cent detection rate.
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