Large-scale vibrating coil magnetometer for the magnetic characterization of bulk superconductors.

This work presents the design and validation of a vibrating coil magnetometer for the characterization of the field dependence of the critical current density of centimeter-sized bulk superconductors as an alternative to the destructive methods typically used. The magnetometer is also shown to be capable of measuring the magnetic moment in an applied field of up to 5 T for diverse magnetic materials, such as soft and hard ferromagnets and high-temperature superconducting pellets. The vibrating coil magnetometer was first optimized using finite element simulations and calibrated using a commercial vibrating sample magnetometer. The vibrating coil magnetometer was benchmarked with hysteresis measurements of a Nd2Fe14B disk made with a commercial hysteresisgraph, showing good agreement between the different setups. The magnetic hysteresis of a YBa2Cu3O7-x superconducting pellet was measured at 77 K, showing a penetration field of 1 T and an irreversibility field of 4 T. The field dependent critical current density of the superconductor was then inferred from the magnetic hysteresis measurements and extrapolated at low fields. Finally, the resulting critical current density was used to successfully reproduce the measured magnetization curve of the pellet at 2 T with finite element simulations.

Alternative-splicing forms of the major phase II conjugating UGT1A gene negatively regulate glucuronidation in human carcinoma cell lines.

The UDP-glucuronosyltransferase UGT1A gene is a major biotransformation gene involved in the metabolism of a vast array of molecules. Recently, we uncovered a new series of alternative spliced isoforms referred to as isoforms 2 or UGT1As_i2 that use an alternative exon 5 (5b). The function of such mRNAs and the corresponding 45 kDa proteins still remains unclear. Although devoid of glucuronosyltransferase activity, UGT1As_i2 are widely co-expressed with the enzymatically active and classical UGT1A isoforms (UGT1As_i1). In this study, we observed abundant signal in human colon tissue samples, predominantly along intestinal crypts. In human cells, UGT1A_i2 proteins are expressed in similar subcellular compartments as UGT1As_i1. Cellular properties of i2-spliced forms were then studied using synthetic small-interfering RNA (siRNA) in two human colon cancer cell lines that show a significant amount of exon 5a- and exon 5b-containing mRNAs and that display enzymatic activities for UGT1As substrates. We observed that siRNA-mediated knockdown of endogenous i2 upregulates cellular glucuronidation activities by 120-170% (P<0.01) for all substrates tested. Functional data support a dominant-negative function for endogenous exon 5b-spliced forms of UGT1A, hence potentially affecting in vivo glucuronidation capacity. This new regulatory strategy may ensure an additional mean to modulate cellular response to endo/xeno stimulus.

Thoracic dimensions at maximum lung inflation in normal subjects and in patients with obstructive and restrictive lung diseases.

OBJECTIVES: To compare the distribution of lung volume at total lung capacity (TLC) among adult men and women known to have normal lung function or chronic obstructive disease or restrictive lung disease (RLD). DESIGN: Five-year retrospective study. SETTING: Review of available clinical pulmonary function testing (PFT) reports and chest radiographs. PATIENTS: Sixty-four patients presenting with normal PFT and chest radiograph findings (normal subjects), 26 patients with severe COPD and increased TLC (COPD group), 29 patients with cystic fibrosis (CF) and increased TLC (CF group), and 19 patients with RLD with a clinical diagnosis of pulmonary fibrosis and a reduced TLC (RLD group). MEASUREMENTS: Average posteroanterior rib cage diameter (PAave), average lateral rib cage diameter (LAave), and average vertical height of the diaphragm (HDIave) were measured using radiography. Normal prediction equations were generated based on stature, body mass index (BMI), age, and sex as independent variables and then used in between-group comparisons. RESULTS: PAave correlated positively with BMI and age but not with height, whereas LAave correlated positively with BMI and height but not with age. HDIave correlated positively with height and age but negatively with BMI. PAave and LAave were smaller and HDIave was greater in women than men having the same stature. In the COPD group and in male CF group patients, BMI was low and only HDIave was greater than in sex-, age-, and height-matched normal subjects, but in female CF group patients, only the rib cage diameters were greater than normal. In the RLD group, PAave and HDIave were smaller than predicted and inversely related to each other, but LAave was normal. CONCLUSION: Variations in maximum lung volume caused by gender, growth, or by lung diseases are nonisotropic and entail substantial changes in chest wall shape.

Complications of trauma care: risk analysis of pneumonia in 10,001 adult trauma patients.

Five year's experience recorded in the adult registry of a Level I trauma center was reviewed to identify all recorded complications. Patients in whom pneumonia occurred were further analyzed for associated risk factors and for potentially preventable occurrence. Of 10,001 patients, 1027 (10%) sustained a total of 1905 complications. Patients with complications were more severely injured (mean Injury Severity Score = 27.5 versus 9.6;P < 0.01). Pneumonia occurred in 392 patients and was the most frequently encountered complication. Mortality for patients with uncomplicated care was 5.8 per cent in comparison with 46 per cent for those with any complications (P < 0.001), and 30.3 per cent for the pneumonia group (P <0.05). Age >65 years, Injury Severity Score >15, Glasgow coma scale score <8, cervical spine fracture with spinal cord injury, Abbreviated Injury Scale >3 for head, chest, and abdomen regions were associated with an increased risk of pneumonia (P < 0.001). Forty-four patients who developed pneumonia (11%) presented without any risk factor. Two of five related deaths could be considered potentially preventable. We conclude that the incidence of complications related to trauma care increases with injury severity and that complications are associated with a significantly higher mortality. The frequency of pneumonia, 11 percent of which were potentially preventable, emphasizes the critical importance of infection control and aggressive pulmonary toilet in the early care of injured patients.

Death from pelvic fracture: children are different.

This study compares outcome from pelvic fractures in children with that of adults. Data for 23,700 children registered in the National Pediatric Trauma Registry (NPTR) were compared with those of 10,720 adults recorded over 5 years in the registry of our level I trauma center. Patients were categorized by open versus closed fracture and by fracture type as defined by a modification of the Key and Conwell system. Outcome was evaluated by mortality rate and incidence of fracture-induced fatal exsanguination. The 722 pelvic fractures recorded in the NPTR represent 3% of the population and is half the frequency represented by the 532 adults evaluated (P < .001). The overall mortality rate was 5% for children and 17% for adults. Two children died of fracture-related exsanguination; there were 18 such deaths among the adults. Pelvic ring disruption was encountered more commonly among adults, and was associated with a significantly higher mortality rate. Patients with initial hemodynamic instability were more likely to die, although children less so than adults. The authors conclude that children do not die of pelvic fracture-associated hemorrhage as often as adults. Massive blood loss in the child occurs most commonly from solid visceral injury rather than from pelvic vascular disruption.

Study on the functionality and molecular properties of the AT4 receptor.

Whereas the role of angiotensin II (Ang II) has been clarified in numerous tissues and cell types, the physiological relevance of its C-terminal (3-8) degradation fragment, angiotensin IV (Ang IV), is unclear. Previously, we characterized a specific binding site for Ang IV in the bovine adrenal cortex and on bovine aortic endothelial cells (BAEC). In the present study, we tried to assess the functionality and mechanism of action of this receptor for Ang IV (AT4 receptor). Our results revealed that none of the classical second messengers (i.e., cAMP, Ca2+, inositol phosphates, nitric oxide or arachidonic acid derivatives) was modified significantly during acute (less than 1 h) stimulation of cells with Ang IV. Under normal culture conditions, BAEC efficiently internalized 125I-Ang IV. After a 2 h incubation at 37 degrees C, acid-resistant binding corresponded to about 50% of total cell-associated radioactivity. This rapid internalization process suggests that the AT4 receptor is a functional protein. With a photoaffinity labeling approach, we revealed some properties of the AT4 receptor that are consistent with those of a growth factor or cytokine receptor.

Characterization of AT4 receptor from bovine aortic endothelium with photosensitive analogues of angiotensin IV.

Newly developed photosensitive analogues of AngIV were used to characterize the AT4 receptor of bovine aortic endothelial cells. The photoactivatable AngIV analogues [N3-Phe6]AngIV and [Bpa6]AngIV displayed high affinities for AT4 receptor, with IC50's of 3.7 +/- 0.3 and 19.1 +/- 3.5 nM, respectively. The radioiodinated ligands showed a good efficiency of photoaffinity labeling demonstrated by high proportions (60-75%) of acid-resistant binding. Covalently labeled receptor was solubilized under reducing or nonreducing conditions and subjected to SDS-PAGE. Under nonreducing conditions, autoradiographies revealed a major band of Mr 186 +/- 2 kDa and a minor band of Mr 241 +/- 6 kDa. The labeling of these bands was completely abolished in the presence of 10 microM AngIV. Under reducing conditions, only the low Mr 186 kDa band was revealed. After endoglycosidase digestion with an enzyme that cleaves N-linked saccharides, the Mr of the denatured AT4 receptor was decreased by 31% to a value of 129 +/- 10 kDa. Kinetic studies revealed a stepwise process of AT4 receptor deglycosylation by endoglycosidase F, suggesting at least two different sites of N-linked saccharides. Mild trypsin treatment of photolabeled endothelial cell membranes released a large fragment of Mr 177 +/- 3 kDa which accounts for about 95% of the whole receptor molecular mass. These results demonstrate that [N3-Phe6]AngIV and [Bpa6]AngIV are very efficient tools for selective photoaffinity labeling of AT4 receptor. We have shown that AT4 receptor is a 186 kDa integral membrane glycoprotein with a very large extracellular domain. These properties are consistent with those of a growth factor or cytokine receptor.