Pregnancy loss and autoantibodies against phospholipid-binding proteins

We investigated the utility of two approaches for exploiting pleiotropy to search for genes influencing related traits. To do this we first assessed the genetic correlations among a set of five closely related quantitative traits (Q1, Q2, Q3, Q4, Q5). We then used the genetic correlations among these five traits both to remove the common genetic effects of the four remaining traits, thereby identifying the unique genetic contribution to each trait, and to extract a synthetic phenotype which exploits the shared genetic information (pleiotropy) among these five traits. After obtaining these conditional traits, we then searched for evidence of quantitative trait loci (QTLs) (using variance component linkage) influencing the unique residual genetic component for each trait as well as those influencing the expression of the synthetic traits. From this work, we conclude that the removal of the common genetic effects of other traits in a group may be of greater utility when the majority of the pleiotropy initially detected between traits is attributable to the shared additive effects of polygenes, rather than to those of major loci. By contrast, decomposition of the genetic covariance matrix to its principal components is a greater utility when the majority of pleiotropy is attributable to major loci.     

Improved Flux Pinning in Melt-Textured YBa2Cu3O7 − δ and ErBa2Cu3O7 − δ Through Chemical Additions

The effects of Ce-based additions (CeO₂ and BaCeO₃) in combination with MgO additions on the magnetic properties of melt-textured YBa₂Cu₃O_{7 ? δ} and ErBa₂Cu₃O_{7 ? δ} have been investigated. The additions lead to improvements in the magnetic properties of both RE-123 compounds compared to samples with either addition alone or with no additions. The Ce–Mg addition combination produces a “peak effect” in the magnetic hysteresis loop without significant T _c degradation. This is postulated to be due to the formation of a new type of pinning center. Both Ce and Mg ions are thought to substitute in the RE-Ba₂Cu₃O_{7 ? δ} lattice, creating defects that produce a “peak effect” in the magnetic hysteresis loop. Mg additions alone lead to a reduced T _c, while Ce additions restore the T _c and enhance the magnitude of the peak.     

Framework for Assessing Robotic Dexterity within Flexible Manufacturing

With growing demand for flexibility in manufacturing processes, interest in dexterous industrial robots is increasing. To facilitate benchmarking, and to assess the suitability of these robots for flexible manufacturing tasks, there is a need to develop new methods of capturing the relevant performance characteristics of industrial robots. This research aims to show that the Boothroyd-Dewhurst (B-D) Design-For-Assembly method, an established method for optimizing manufacturing processes, can be effectively adopted to form the basis of a comprehensive robotic dexterity assessment within flexible manufacturing. A comparative study is conducted which shows that the B-D classification tables offer the most comprehensive solution due to the range of operations and artifacts considered. Building on these tables, a framework is developed for determining the suitability of a robot system within flexible manufacturing operations. In a sample test-case scenario involving a pick-and-place operation, the framework is shown to produce an accurate estimate of robot performance that can be easily compared to human data. The framework establishes a link between manufacturing operations and robot performance metrics, which addresses the current difficulty in robot integration and highlights the framework’s potential for adoption within flexible manufacturing.     

Adenovirus-mediated gene transfer of inhibitors of apoptosis protein delays apoptosis in cerebellar granule neurons

The inhibitor of apoptosis (IAP) family of antiapoptotic genes, originally discovered in baculovirus, exists in animals ranging from insects to humans. Here, we investigated the ability of IAPs to suppress cell death in both a neuronal model of apoptosis and excitotoxicity. Cerebellar granule neurons undergo apoptosis when switched from 25 to 5 mM potassium, and excitotoxic cell death in response to glutamate. We examined the endogenous expression of four members of the IAP family, X chromosome-linked IAP (XIAP), rat IAP1 (RIAP1), RIAP2, and neuronal apoptosis inhibitory protein (NAIP), by semiquantitative reverse PCR and immunoblot analysis in cultured cerebellar granule neurons. Cerebellar granule neurons express significant levels of RIAP2 mRNA and protein, but expression of RIAP1, NAIP, and XIAP was not detected. RIAP2 mRNA content and protein levels did not change when cells were switched from 25 to 5 mM potassium. To determine whether ectopic expression of IAP influenced neuronal survival after potassium withdrawal or glutamate exposure, we used recombinant adenoviral vectors to target XIAP, human IAP1 (HIAP1), HIAP2, and NAIP into cerebellar granule neurons. We demonstrate that forced expression of IAPs efficiently blocked potassium withdrawal-induced N-acetyl-Asp-Glu-Val-Asp-specific caspase activity and reduced DNA fragmentation. However, neurons were only protected from apoptosis up to 24 h after potassium withdrawal, but not at later time points, suggesting that IAPs delay but do not block apoptosis in cerebellar granule neurons. In contrast, treatment with 100 microM or 1 mM glutamate did not induce caspase activity and adenoviral-mediated expression of IAPs had no influence on subsequent excitotoxic cell death.     

Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery

We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute.     

Regulation of early cholesterol biosynthesis in rat liver: effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activities

BACKGROUND: Sclerosing peritonitis (SP) is a rare but serious complication of peritoneal dialysis (PD). Small-bowel obstruction (SBO) due to encapsulation, dense adhesions, or mural fibrous is characteristic, often associated with peritonitis. The aim of the study was to determine the incidence, clinical features, effect of duration of dialysis, and other possible aetiological factors in severe SP. METHODS: All dialysis units in Australia were surveyed for possible cases up to 1994. Patients were included if there was either surgical or radiological evidence of sclerosing encapsulating peritonitis or SBO with tanned or thickened peritoneum in the absence of other causes of SBO. RESULTS: Fifty-four patients were analysed. The duration of continuous PD was mean 52 +/- 30 months, median 48 months and range 8-127 months. Nineteen cases were diagnosed between 1980 and 1989 and 35 between 1990 and 1994, giving mean annual incidences 1.9 and 4.2 per 1000 PD periods respectively. The overall prevalence was 0.7%, which increased progressively with the duration of PD being 1.9, 6.4, 10.8, and 19.4% for patients on dialysis for > 2, 5, 6 and 8 years respectively. Sclerosing encapsulating peritonitis was diagnosed in 87% of cases, SBO in 92%, and haemoperitoneum in 8%. Peritoneal calcification was present in seven cases, all of which had been on PD > 7 years. Peritonitis was associated with 38% of cases with fungal infection in 7%. Treatment with immunosuppression in five patients appeared to result in a favourable outcome in three. The mortality rate was 56%. CONCLUSION: Severe sclerosing peritonitis is a serious complication of peritoneal dialysis and there is a time dependent increase on CAPD.