Fluorescence flow cytometry of human leukocytes in the detection of LDL receptor defects in the differential diagnosis of hypercholesterolemia

A flow-cytometric method with fluorescence-labeled monoclonal antibodies (MABs) against the low density lipoprotein (LDL) receptor (C7A MAB) or 3,3'-dioctadecylindocarbocyanin-iodide (DiI) LDL has been developed that allows the quantification of LDL receptors on leukocytes and the identification of patients with familial hypercholesterolemia (FH) within 48 hours. Leukocytes were isolated from 10 mL anticoagulated blood by density gradient centrifugation. To induce maximal expression of LDL receptors, mononuclear cells were preincubated with either phytohemagglutinine (PHA) or lipoprotein-deficient serum (LPDS). LPDS-treated monocytes provided a more homogeneous cell population with regard to LDL receptor activity than did the PHA-treated lymphocytes; they also provided a greater discrimination between the fluorescence of the receptor probes and cellular autofluorescence. The C7A MAB was able to compete for DiI LDL binding by about 40%. In competition with unlabeled LDL, DiI LDL revealed linear binding, indicating an affinity similar to native LDL. The binding characteristics of DiI LDL were also similar to 125I-LDL binding. LDL isolated from familial defective apolipoprotein B-100 was not able to compete for DiI LDL binding on monocytes, whereas native LDL reduced it by about 80%. In monocytes from FH heterozygous patients, the cellular mean fluorescence using either C7A MAB or DiI LDL at 4 degrees C was 30% to 70%; in FH homozygotes, cellular mean fluorescence was less than 20% of that in monocytes from normal individuals. In patients with familial defective apolipoprotein B-100 antibody binding was normal, but one patient's own LDL failed to compete with normal DiI LDL for 4 degrees C binding on U937 test monocytes. Patient monocytes having internalization defects showed normal 4 degrees C DiI LDL binding, but at 20 degrees C cell-associated fluorescence was reduced by about 40%. In our study 384 hypercholesterolemic patients (preselected according to serum cholesterol levels, clinical symptoms, and family history) were analyzed for LDL receptor expression using the C7A MAB-based assay. In 71.8% of the patients with cholesterol levels higher than 300 mg/dL, an LDL receptor deficiency was observed. Apolipoprotein E isoforms and lipoprotein[a] were found to be independent from the LDL receptor status. In some patients with high cholesterol levels but normal LDL receptor expression with the C7A MAB assay, LDL receptor defects could be diagnosed when either reduced binding or internalization of DiI LDL or familial defective apolipoprotein B-100 was detected.(ABSTRACT TRUNCATED AT 400 WORDS)     

High-speed InGaP/GaAs HBTs with a strained InxGa1-xAs base

A self-aligned InGaP/GaAs heterojunction bipolar transistor with a compositionally graded In_xGa_1-xAs base has been demonstrated with f_T=83 GHz and f_max=197 GHz. To our knowledge, these results are the highest reported for both parameters in InGaP/GaAs HBT's. The graded base, which improves electron transport through the base, results in a DC current gain and a cutoff frequency which are 100% and 20% higher, respectively, than that achieved by an identical device with a nongraded base. The high f_max results from a heavily doped base, self-aligned base contacts, and a self-aligned collector etch. These results demonstrate the applicability of InGaP/GaAs HBT's in high-speed microwave applications     

Bias, frequency, and area dependencies of high frequency noise inAlGaAs/GaAs HBT's

The noise figure of the heterojunction bipolar transistor (HBT) in the microwave frequency range is studied, and an improved physical noise model is developed. Unlike the conventional high frequency noise model, which considers only the bias current dependence, the present model includes both the effects of voltage and current on the noise behavior. In addition, the frequency- and area-dependent natures of the HBT noise at very high frequencies are incorporated in the model. It is found that the voltage dependence of the high frequency noise in the HBT results from the self-heating effect, which gives rise to a higher HBT lattice temperature than the ambient temperature. Also, the free-carrier transport delay time must be considered to properly model the frequency dependence of noise since the inverse of this time is comparable with the frequency. Furthermore, the area dependence of noise is dominated by changes in the base resistance and emitter-base junction capacitance. Results for the minimum noise factor calculated from the model compare favorably with those obtained from measurements     

High-speed InP/lnGaAs heterojunction bipolar transistor utilizing nonalloyed contacts on n+-InP contacting layers

We have demonstrated a high-speed InP/lnGaAs heterojunction bipolar transistor with nonalloyed TiPtAu contacts on n⁺-InP emitter and collector contacting layers. The use of SiBr₄ as a silicon doping source enabled the formation of low resistance (p_c <2 × 10⁻⁶Ω. cm²), nonalloyed TiPtAu contacts to the heavily doped (n = 2 × 10¹⁹ cm⁻³) InP contacting layers. A device with a 3 × 10 Μm² emitter contact exhibited excellent dc characteristics and had ƒ_T = ƒ_max = 107 GHz. Emitter and collector resistances are compared to a device with InGaAs contacting layers.     

Effect of Interfacial Roughness Parameters on the Fiber Pushout Behavior of a Model Composite

The effect of interfacial roughness on the frictional sliding in composites has been studied using fiber pushout and pushback tests on a model composite of Plexiglas rods in an epoxy matrix. Different extents of roughness were introduced on the Plexiglas rods and the resulting roughness profiles measured. The roughness profiles were characterized using six different roughness parameters. An attempt was made to find a correlation between the sliding resistance and the selected roughness parameters. A parameter defined as the maximum coefficient in the Fourier transform of the roughness profile was found to yield the best correlation. If the roughness introduced is periodic, then the pushout traces exhibit periodic dips, but the magnitude of this periodic dip is significantly smaller than the seating drop obtained from pushback tests.     

Underlying design advantages for GaN MOSFETs compared with GaN HFETs for power applications

This study investigates the underlying reasons and quantifies the advantages the GaN MOSFET has over the GaN HFET for high voltage and power applications. Calibrated simulations with equivalent material model files show that equivalent dimensioned devices are capable of producing similar on-state modes of operation, and achieve similar effective mobility at equivalent larger electric fields. However, during sub-threshold operation, the GaN MOSFET is shown to contain a much lower carrier concentration than the GaN HFET. This prolongs the breakdown avalanche effect in the GaN MOSFET (3500 V) by roughly five times larger than the GaN HFET (600 V) for devices of similar dimensions. Implementing the MOS structure can potentially resolve fundamental constraints for high voltage power applications caused by current device architects.     

Inversion MOS capacitance extraction for high-leakage dielectricsusing a transmission line equivalent circuit

Accurate measurement of MOS transistor inversion capacitance with a physical silicon dioxide thickness less than 20 Å requires correction for the direct tunneling leakage. This work presents a capacitance model and extraction based on the application of a lossy transmission line model to the MOS transistor. This approach properly accounts for the leakage current distribution along the channel and produces a gate length dependent correction factor for the measured capacitance that overcomes discrepancies produced through use of previously reported discrete element based models. An extraction technique is presented to determine the oxide's tunneling and channel resistance of the transmission line equivalent circuit. This model is confirmed by producing consistent C_0x measurements for several different gate lengths with physical silicon dioxide thickness of 9, 12, and 18 Å     

Predictors of blood loss after coronary artery bypass grafting

OBJECTIVE: To assess the predictive value of variables possibly associated with blood loss after coronary artery bypass grafting (CABG). DESIGN: A prospective study. SETTING: A university hospital. PARTICIPANTS: Eighty-nine patients scheduled for elective CABG. INTERVENTIONS: Blood samples were drawn before and after surgery. Chest tube drainage was measured hourly until removal of drains. MEASUREMENTS AND MAIN RESULTS: Activation of coagulation and fibrinolysis, routine clotting tests, and expression of platelet surface antigens were analyzed using flow cytometry. A significant correlation was found among blood loss and activated partial thromboplastin time, fibrinogen, prothrombin fragment 1 + 2, D-dimers, platelet count, GPIb and P-selectin expression on platelets, use of internal thoracic artery, cross-clamp time, and thrombin-antithrombin III complex. In a multiple regression model, glycoprotein (GP) Ib expression on platelets, platelet count, use of internal thoracic artery, and D-dimers were significantly associated with blood loss. Logistic regression analysis showed that GPIb and D-dimers predicted an increased blood loss with a positive predictive value of 73% and a negative predictive value of 91%. CONCLUSIONS: Postoperative D-dimers and GPIb expression may be useful to exclude nonsurgical causes in bleeding patients after CABG.     

Thermal characterization of thermally-shunted heterojunctionbipolar transistors

Heterojunction Bipolar Transistors (HBTs) are potentially useful in a number of microwave applications, but they are severely limited by a current distribution instability caused by electrothermal interaction and the use of a low thermal conductivity substrate. A novel thermal management technique called “thermal shunting” has been developed to reduce thermal resistance and junction temperature non-uniformity. Thermal resistance measurements for thermally-shunted devices are presented. Specific thermal resistance measurements as low as 2.6×10^-4°C-cm²/W (147°C/W at 0.1 W for a device with a 177 μm² emitter area) have been obtained. Thermal resistance values obtained for thermally-shunted HBTs are substantially lower than those reported for conventional HBTs     

Characterization and modeling of AlGaN/GaN MOS capacitor with leakage for large signal transistor modeling

Dual mode AlGaN/GaN metal oxide semiconductor (MOS) heterostructure field-effect transistor (HFET) devices were fabricated and characterized. In HFET mode of operation the devices showed an f/sub t//spl middot/L/sub g/ product of 12GHz/spl middot//spl mu/m at Vgs=-2 V. The AlGaN devices showed formation of an accumulation layer under the gate in forward bias and a f/sub t//spl middot/L/sub g/ product of 6GHz/spl middot//spl mu/m was measured at Vgs=5 V. A novel piecewise small signal model for the gate capacitance of MOS HFET devices is presented and procedures to extract the capacitance in presence of gate leakage are outlined. The model accurately fits measured data from 45MHz to 10GHz over the entire bias range of operation of the device.