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Resolution of current controversies regarding the nature and functional roles of the oligomeric forms of G-protein coupled receptors (GPCRs) demands that experimental methods are both quantitative – i.e., they allow determination of size, geometry and stability of oligomers under varying experimental conditions – and applicable to receptors within their cellular milieu. Standard microscopy methods based on light do not provide the resolution necessary to resolve membrane receptor complexes, while techniques based on other contrast mechanisms (e.g., electron microscopy or atomic force microscopy) require sample destruction and fixation. Fortunately, techniques that exploit physical properties of fluorescent molecules, such as their ability to transfer excitations to an unexcited nearby fluorescent molecule (as in FRET spectrometry) and spatial or temporal fluctuations in the fluorescence intensity (fluorescence correlation spectroscopies and photon counting histograms) driven by aggregation and diffusion are capable of increasing the spatial and temporal resolution of all optical microscopies by several orders of magnitude. In this chapter, we overview the physical principles underlying such techniques, their comparative advantages and limitations, as well as their application to quantitative analysis of GPCR oligomerization in living cells.

A microelectromechanical systems (MEMS) actuator was selected to study the effects of packaging induced stress on device reliability. In this work, MEMS devices were obtained and packaged using cyanate ester, 96.5/3.5 Sn/Ag, and 92.5/5/2.5 Pb/Sn/Ag die attachment materials. The die attachment materials were then cured or reflowed appropriately and cooled to room temperature which induced stress through the coefficient of thermal expansion mismatches between the silicon die and alumina package. In this work, a MEMS microengine developed at Sandia National Laboratories, which is a device that has been well studied, was selected as a test vehicle to understand the effects of various die attachment solders and related processes parameters on the ultimate functionality of the packaged MEMS microengine. Particularly, the operational lifetime of these devices was measured by testing these devices to failure. These lifetimes were then compared with baseline values to determine the effect of stress on these devices. The maximum stress values observed in these studies ranged from 11–23 MPa based on the die attachment material used for cyanate ester to Pb/Sn/Ag solder, respectively. About 50% of the total population tested failed between 105 and 106 cycles, while 25% failed above 106 cycles and the remaining 25% failed below 105 cycles. The reliability results agreed well with previous results. The effect of stress did not seem to adversely affect the device lifetimes for this class of MEMS device, suggesting that these ranges of solders can be safely used to package MEMS devices.

Nanomechanical silicon cantilever beam test structures were fabricated from silicon-on-insulator wafers using electron beam lithography. A scanning probe system in the form of an atomic force microscope was used to measure their mechanical properties in a non-destructive evaluation approach. It is important to note that, despite the nanometer size of the silicon cantilever beams in the [100] direction, Young's modulus remained unchanged from the bulk value: 179 GPa. We believe that the fabrication processes did not induce any major structural modifications to the basic building blocks of silicon. Hence the Young's modulus was measured to be the same as that of the bulk silicon, which is important for designing predictable structures at nanometer scale.

As applications continue to demand increasingly higher optical output power and longer lifetime, thermo-mechanical stresses on dissimilar materials interfaced for packaging pose an ever-growing challenge for the realization of a durable system. Particularly important for an epitaxy-down configuration is the die-attachment interface, which is desired to be defect free and stress managed for reliable optical alignment. A knowledge of the changes in the physical defect density and magnitude of the thermo-mechanical stress present in the active region as a function of the fabrication process and aging is crucial to an understanding of the influence of the process parameters and operating conditions on device performance and reliability. In this study, we investigated high power laser diode array packages aged under various conditions. Microscopic defect analyses of the die attachment interface and device stress were carried out using primarily metallography, scanning electron microscopy, scanning acoustic microscopy, microhardness, and micro-Raman spectroscopy. It was noted that the intermetallic compounds and microscopic physical defects at the die attach interface are detrimental to transient heat transfer, and thus, overall package reliability. Using micro-Raman spectroscopy, we found that tensile stress near the bar-package interface increases with aging for the first few hundred hours and then decreases with further aging.

Using numerical, analytical and experimental methods, we evaluate the structural and thermal performance of a large, 1 cm×1 cm, GaAs die, flip-chip attached to 2.54 cm×2.54 cm diamond substrates. In agreement with numerical predictions, the GaAs dice's induced stress during the attachment process — 37Pb/63Sn solder reflow and high-temperature underfill cure — is below the fracture strength of GaAs. However, as numerically predicted, the stress in the dice is higher for underfilled chips. This larger stress is measured indirectly through stylus profilometry where we experimentally determine the die deflection. The underfilled chips deflect more, which correlates with higher die stress. Both analytical and numerical results confirm this conclusion. Experimental and numerical thermal studies demonstrate the importance of the case-to-ambient thermal resistance (θca). For our package, diamond offers tremendous thermal advantage only for θca values less than 1°C W−1 and offers little to no advantage for θca values greater than 10°C W−1.

Diamond-coated tools can greatly improve the productivity of machining highly abrasive materials such as high silicon–aluminium alloys used in the automotive industry. Cemented-carbide diamond-coated tool inserts have not become an off-the-shelf product owing to several difficulties including insufficient adhesion of diamond to the substrate and questionable reproducibilty in their machining performance in the manufacturing. In order to overcome these difficulties, a better understanding of the effects of the chemical vapour deposition (CVD) conditions such as methane concentration, reactor pressure and substrate temperature is important. In this work, cemented tungsten carbide tool inserts with 6 wt% Co (WC–Co) were coated with diamond films deposited at five different methane concentrations (1–9 vol%). Here we present preliminary results of the effect of methane concentration variation on the following physical properties of the diamond coating: surface morphology; crystal structure; chemical quality; surface roughness; residual stress. The results indicate that the best physical properties of diamond-coated tool inserts using hot-filament CVD are achieved with diamond coatings deposited at methane concentrations ranging from 1 to 3%.

CVD diamond-coated cemented carbide inserts are on the verge of becoming the next generation of tools used for high-speed hard-cutting processes. Good adhesion of the diamond coating, and consistency on the micro-level of the CVD process are the current challenges which to a certain extent prevent these coated tools from becoming an off-the-shelf product. In this work, we report preliminary results of the effect of methane concentration variation on the surface roughness, adhesion, residual stress, and turning performance for diamond-coated inserts. Cemented carbide inserts with 5% cobalt were coated with diamond films using an inexpensive hot filament CVD system. The methane concentration in the reaction mixture was varied from 1 to 9%. The results suggest that the optimal mechanical performance of diamond-coated inserts can be achieved when diamond is deposited at a methane concentration of about 3%.

A hairline crack was introduced in a 27.9 cm long by 7.62 cm wide by 1.3 cm thick (11 by 3 by 0.5 in.) 6061-4 aluminum specimen by repeated bending. The size of the crack was limited by stopping the bending at the initial stage of crack formation. Measurements were then made using an AC magnetic bridge which detected the presence of the crack and enabled characterization of its form. The extent, the orientation, and the depth from the surface along the crack length were obtained from the measurement. This paper outlines the principle of the bridge operation and details related to interpreting the output from the bridge as the bridge is moved over the surface of the aluminum specimen. Verification of the bridge measurements was made by destructive evaluation of the specimen using a scanning electron microscopic examination.

A general, integral expression is developed which relates measurements of the variations of the imaginary component of complex‐ reluctance with frequency to stress profiles near the surfaces of metals. The technique should yield either applied or residual stress profiles produced, for example, by heat‐treating, metal‐working, fatigue, or peening. It may even be applicable to carburizing. The technique of measurement cancels out the effects of any pre‐treatment residual‐stress profile (subject to the assumption of superposition). The general, integral expression is induced from the results of measurements on a steel bar which is subjected to both tensile tests and bending tests.

Knowledge of the mechanical behavior of strategically important materials such as silicon at nano scale is the key for building next generation devices. In this paper, we investigate the Young’s Modulus of nanomechanical beams [1-8 mm long, 200-400 nm wide, and 193 & 255 nm in thickness] fabricated from silicon-on-insulator (SOI) wafers. The beams of different dimensions were defined in PMMA resist using e-beam lithography. A layer of chrome deposited using lift-off technique, acted as an etch-mask for silicon to fabricate the beams by using RIE. The samples were dipped in BOE (Buffered Oxide Etch) to etch the oxide underneath and the beams were released using critical point drying. Using a Scanning Probe System, nanomechanical beams were bent using AFM silicon tapping mode probes. A controlled amount of force was applied by varying the voltage applied to the Z-axis piezoactuator. The values of beam deflection and the net force applied enabled us to plot the Load vs. Displacement graph for the bending of the nanomechanical beams. Using Euler - Bernoulli beam bending equations, the Young’s Modulus of the Silicon beams was measured to be 174 GPa. This value agrees within 5% of the known value of bulk silicon Young’s modulus of 169GPa. Thus we conclude that the value of Young’s modulus of Si beams does not change when the size is reduced to nanometer regime.

In this paper the authors describe the design considerations including force and tolerance analysis and mechanism and tip design, for a novel, dynamic scanning probe microscopy tip directly insertable into today’s existing atomic force microscopy tools. This tool is the first of its kind and is a major step in the field of nanomanufacturing enabling the use of nanomechanical machining operations for nanostructure top-down manufacturing. The application of this device is the nanomechanical drilling and milling of III-V semiconductor substrates for various applications such as nanovias for electrical interconnection of next generation electronic and photonic applications, as well as reservoirs and capillaries for nano-fluidics. Results to date indicate that device performance parameters allow a normal drilling force of 25 μN, tangential drilling force of 35 μN, maximum rotational speed of 100,000 rpm, and minimum machined feature size of less than 200 nm. This device is currently being fabricated at Sandia National Laboratories, SUMMIT MEMS foundry and being packaged at the University of Arkansas, Fayetteville High Density Electronics Center (HiDEC).Copyright © 2002 by ASME

High power semiconductor laser diodes are finding increasing applications in diverse areas such as the biomedical field, materials processing, cosmetics, etc. Dissimilar materials integration and thermal management are some of the primary challenges in the fabrication and packaging of reliable laser diode systems. For example, in a specific case, a high power diode must be mounted with its epitaxy-side down, so as to achieve efficient heat transfer. The device and package junction, particularly the die attach interface, is desired to be void-free (i.e., micro-defect free), stress-managed, and contamination-free for uniform optical delivery and reliable optical alignment. Soft solders used in optoelectronic applications are typically subjected to extreme service conditions that may exceed two-thirds of the melting point. As a result, it is expected that the solder microstructure will be metastable and subjected to nearly constant modification during processing and device operation. In this study, we investigated high power laser diode packages aged under various conditions. Die attach interface, device stress, and microscopic defect analyses were carried out using primarily metallography, scanning electron microscopy (SEM), scanning acoustic microscopy, and micro-Raman spectroscopy. It was observed that the intermetallic compounds and microscopic physical defects at the die attach interface are detrimental to transient heat transfer, and thus, overall package reliability. Further, accurate device modeling can be used to assist in the overall understanding of the effect of packaging-induced stress on the performance and reliability of semiconductor lasers. The purpose of this modeling work was to better understand the interplay between electrical, optical, mechanical, and thermal effects in the operation of laser diodes. Micro-Raman spectroscopy was employed to explore the degradation of high power lasers due to mechanical stresses that appear in an active region of the diode during its growth, packaging, and operation. Using micro-Raman spectroscopy, we found that, although stress increases with aging, the shape of the stress profile and the strength changes randomly from one active region of the diode to another.

In an effort to better understand and thereby utilize laser processing, an existing code describing laser-metal (aluminum) interaction is modified to describe laser-ceramic (diamond) interaction. Comparisons between our modified code (diamond target) and the original code (aluminum target) highlight similarities and differences between laser-ceramic and laser-metal processing. Gas breakdown effects, which are expected for the simulated short (time duration), high energy laser pulses, are observed in both codes. Due to the lower sublimation heat of aluminum (1.1×104J/g) compared to diamond (5.3×104J/g), aluminum vaporizes more quickly and exhibits a faster expansion speed (1.4×107 cm/sec compared to 8×106 cm/sec for diamond) in the early stage of the laser pulse. Because aluminum requires significantly more energy to fully ionize than does carbon, our simulations show that the diamond plasma is fully ionized (6 of 6 electrons per atom) and the aluminum plasma is partially ionized (11 of 13 electrons per atom).

The standard 55-gallon barrel is frequently used for storage of hazardous chemicals and low-level radioactive materials. Corrosion on the inner surface of the barrels produced by the stored materials may produce wall thinning. Wall thinning may be a problem either in long-term storage or where the barrels must be moved. Ultrasonics could determine the degree this thinning, but the nature of the stored material may discourage the use of the couplant associated with ultrasonics. Electromagnetic fields suggest a way to detect wall thinning rapidly and without the use of couplant.

Alloy 600 tubing is in widespread use in steam generations of nuclear power plants, due to its good high temperature corrosion resistance. It is, however, susceptible to a variety of corrosion damage mechanisms. One of these is tress corrosion cracking (SCC).

It is well known that magnetite builds on the outside of boiler and steam generator tubes. Low-frequency (10 kiloHertz) eddy-current testing (ECT) has been used in attempts to quantify magnetite deposits on alloy 600 steam generator tubes. At this frequency, ECT has some sensitivity to the presence of magnetite on the outside of the tube with measurements made inside the tube. However, it has been historically impossible to resolve differences in deposit thickness, a quantity of some interest to power plant operators. ECT can be further inhibited by layers of copper which may be deposited on the outer surface of Inconel tubing. AC magnetics (ACM) may be conveniently operated at a few hundred Hertz where the small thicknesses of Inconel and the copper deposits are essentially transparent to the electromagnetic fields. The problem then becomes detection of magnetite at large lift off. Here again, ACM is a good technique to use. Preparatory to the design of an ACM probe to fit within steam generator tubing, a feasibility study was conducted which is described here. Flat copper-cladded Inconel plates were used to simulate the tubing, and magnetite of various thicknesses were placed on the side opposite a magnetic-circuit gap. The results indicate that the depth of magnetite through Inconel and copper can be quantified through the use of ACM to about 10 mm.

The high thermal strains that generate during chemical vapor deposition (CVD) of diamond coatings on carbide inserts result in high compressive thermal residual stresses in the diamond near the coating interface. These stresses are believed to increase the strain energy at the interface leading to coating failure. To help predict CVD diamond adhesion characteristics to carbide inserts, quantifying such residual stresses becomes important. A three dimensional finite element model was constructed for a commercial cemented carbide tool insert coated with a 20μm film of CVD diamond and the interfacial thermal residual stresses at the rake and flank regions computed. A 2-D axi-symmetric contact model was constructed to evaluate the effectiveness of mircohardness indentation as an appropriate adhesion test for CVD diamond coatings. Superposition of the residual stresses and the stresses generated by indentation just before cohesive brittle failure of the coating revealed that the combined shear and peel stresses were lower than those originally present due to residual stresses alone indicating that the indentation method may not be a useful technique for determining adhesion.

Nuclear reactor pressure vessels are clad with a layer of stainless steel approximately 6 millimeters thick. The characteristics of the steel of the pressure vessels are known to change with cumulative radiation exposure from the operating reactor. In situ nondestructive determination of the extent of the changes of the steel characteristics must be made through the stainless-steel cladding. Preliminary tests described here indicate that AC magnetic bridges can differentiate among steels of differing characteristics through stainless cladding.

Coil eddy-current (CEC) technology generates real and complex reactances of the search coil. These reactances are frequently plotted in a complex-impedance (C-I) plane with inductive reactance as the ordinate and resistance as the abscissa. This plane is a useful tool in nondestructive evaluation (NDE), and it is known to virtually all NDE technicians using electromagnetic fields. The complex-impedance plane is generally used to establish the operating conditions for particular eddy-current coils and for particular NDE problems. It can also be used to establish the effect of lift off and to identify flaws.

Relative measurements of real and imaginary reluctances were made as a function of sample thickness on both rolled and cast 6061 aluminum samples using an ac magnetic bridge. Samples were both nonannealed and annealed. Evidence was developed that the imaginary reluctance (which is shown here to respond to the conductivity of samples) responds more to the bulk properties of the samples while real reluctance apparently responds more to surface conditions such as surface residual stress.

AC magnetic bridges offer a technique for continuous electromagnetic scanning of surfaces and lap seams of aging aluminum aircraft to detect material losses due to corrosion. AC magnetic bridges are particularly responsive to changes in conductance because nearly all the electromagnetic field generated is in contact with the sample as compared with conventional eddy-current devices where the high reluctance of that portion of the magnetic field not in contact with the sample has a tendency to mask the small portion of the field in contact with the sample. Further, the eddy-current technique masks the effect of the electromagnetic interaction with the sample through the requirement that the changes produced by changes in the sample be detected in series with the impedance of the eddy-current coil. This latter effect requires the use of relative high frequencies in conventional eddy-current devices. Use of the ac magnetic bridge (the bridge) solves all of these problems while providing the physical convenience of conventional eddy-current scans if such a scans were effective. The frequencies used for bridge operation are usually of the order of 100 Hz to 20 kHz and offer greater sample penetration than conventional eddy-current devices which usually operate well above this range. Further, ac magnetic bridges maintain their sensitivity to material loss at values of lift off of 20 mils or greater, well above the usual values of paint coating thicknesses.

The effects of sample thicknesses, frequencies, and values of lift-off on real and imaginary reluctances for a modified ac magnetic bridge were found for aluminum. Aluminum test samples with thicknesses varying between 0.406 and 6.35 millimeters were scanned at values of lift-off ranging from 0.1 to 0.38 millimeters and at frequencies between 200 and 5000 Hz.

Hidden corrosion in the seams or below the skin of an aluminum aircraft results in the loss of material and therefore affects the net conductance as measured at the seam or skin surface. This loss of conductance has been detected through the use of electromagnetic techniques, for example, eddy-current techniques [1].

To optimize the sensitivity and minimize lift-off effects of electromagnetic NDE devices requires an understanding of the source and distribution of electromagnetic fields. This understanding is particularly difficult when conductive devices other than the sample are in the vicinity of the field. Such is the case with the modified AC magnetic bridge [1] which has a conducting insert in the vicinity of the gap in proximity to the sample.

The finite element method was used to simulate glacier flow problems with particular examples given for the flow behavior of the Greenland ice sheet and the Wilkes 1ce cap In Antarctica. The proble...

In this paper a finite element formulation for determining the finite deflection of thin bars is presented. The nonlinear stiffness equations are generated after simple approximate expressions involving the nodal parameters are used to replace the nonlinear terms in the energy functional. The procedure used results in a simplified set of nonlinear algebraic equations which are more amenable to solution than the equations usually presented. The applicability and accuracy of the method together with an evaluation of three incremental solution techniques, a step by step method, a one step Newton-Raphson procedure, and a variable interpolation technique is demonstrated by solving a cantilever beam with a point load acting on the end. Curves showing the sensitivity to increment size and to the number of elements are also presented. The results indicate that the formulation is accurate and inexpensive in terms of computational effort.

A 6-year retrospective investigation elicited patient response to wearing Molloplast-B-lined dentures with the following results: 1. For nearly all the patients wearing a Molloplast-B-lined denture, their ability to wear it comfortably outweighs its disadvantages. 2. Nearly all the patients (95.4%) would elect to have a new soft-lined denture should their present one need replacement. 3. Nearly all the patients (93%) thought that their soft-lined dentures were more comfortable than their previous conventional acrylic resin ones. 4. Molloplast-B-lined dentures offered comfort to a significant number of patients in this study who had had a history of chronic discomfort with the wearing of conventional acrylic resin dentures. 5. The presence of a retracted tongue habit is likely to decrease the patient's satisfaction with the dentures.

The Antarctic ice sheet has almost no net annual ablation on its surface, so most mass losses are by iceberg calving along its perimeter, which may be either grounded in shallow water or floating in deep water. An ice cliff forms along the perimeter in both cases. Wave action undercuts ice margins in the tide-water zone along beaches, and causes coastal calving if the rate of undercutting compares with the forward ice velocity. If the ice velocity is sufficiently greater, the ice sheet advances into deeper water and becomes a float at depths of 200 to 300 m (Robin 1979). A floating ice shelf then forms and icebergs calve along the ice front. Iceberg calving along this ice front may be due to several causes (Holdsworth 1977,Robin 1979). Since iceberg calving, either from ice shelves or in the tidewater zone of beaches between ice shelves, is the principal ablation mechanism of the Antarctic ice sheet, it is important to understand calving dynamics quantitatively. This paper presents the results of a finite-element examination of calving along floating margins of the ice sheet.

An adaptive procedure for selecting the step size when incremental or continuation methods are used to solve sets of non-linear equations is presented. The increment size is limited by requiring the corrective iteration procedure employed to reduce the drifting error to be within a contractive boundary at each level. The usefulness of the procedure is extended by the development of a set of conditions for detecting impending divergence of the corrective iteration process. These conditions, used in conjunction with the step size selection procedure permit the continuation of the solution through highly non-linear regions and also provide a simple means of isolating a limit point, if one exists. Two additional benefits of the procedure are an effective convergence criterion for terminating the iteration process and a simple means for switching between the Newton-Rephson and modified Newton-Raphson iteration procedures. The paper concludes with a number of example problems, three are hyperelastic bodies at finite strain and the final example is the large displacement analysis of an elastic beam. The results illustrate that the procedure is computationally inexpensive, using only information normally obtained in a non-linear analysis, flexible in the sense that a dense or sparse distribution of points along the total solution curve may be obtained, and effective, normally requiring less total computational effort than a constant step size procedure.

It is shown how the elasticity equations can be formulated in terms of a general procedure of abstract analysis, called the projective method, for constructing an approximate solution. This allows the many studies of convergence and uniqueness of solutions which have been made in modern mathematics to be applied to the elasticity problem. The abstract formulation also suggests an organizational scheme for generating a computer code. A computer code for hollow or solid cylinders of arbitrary cross section was developed and several numerical examples are presented. The procedure is computationally advantageous for the class of problems under consideration because of the relatively small number of equations that must be solved as compared to the finite element method. The results presented demonstrate the accuracy of the method.

An investigation of the behavior of metals during asixymmetric extrusion using the finite element method is presented. Flow characteristics as functions of die shape. die-workpiece interface fricti...

The organic mercurial p-chloromercuribenzensulfonic acid (PCMBS) reversibly increases fluxes of sodium and potassium across the human red blood cell membrane. We examined the effect of different monovalent anions on cation fluxes stimulated by PCMBS. A substantial portion of the fluxes of both cations was found to have a specific anion requirement for chloride or bromide, and was not observed when chloride was replaced by nitrate, acetate or methylsulfate. The chloride-dependent component of the cation fluxes was only observed when the cells were exposed to PCMBS concentrations of 0.5 mM or greater. Furosemide (1 mM) did not inhibit the PCMBS-stimulated cation fluxes. The observed anion specificity is directly associated with the transport process rather than PCMBS binding to the membrane. A portion of the potassium transport stimulated by PCMBS appears to involve K+-K+ exchange; however, Na+ + K+ cotransport is not stimulated by this sulfhydryl reagent.

The finite deflection analysis of flexible bars subjected to vertical loads as well as the prediction of the buckling load and post-buckling response in the case of horizontal loading has attract the attention of numerous researchers. Publications related to large deflections of slender beams are referenced in and the monograph contains several applications as well as additional references to previous work. In the present note an efficient finite element procedure is developed for the problem of the elastica including variable loading and foundation stiffness. The effectiveness of the procedure is demonstrated by considering a number of example problems. Because of the generality of the finite element method extensions to more general problems than those presented here can easily be accomplished.

This paper contains a procedure for continuing the solution of nonlinear structural analysis problems past limit and branch points when using the Newlon-Raphson or the modified Newton-Raphson methods in conjunction with incremental loading. The singular or ill conditioned Jacobian which arises at or in the vicinity of critical load points is eliminated by adding positive values to select diagonal elements of the Jacobian. A technique for determining which elements to modify together with a method for efficiently determining the optimum magnitude of the modification for minimum solution error are developed. The effectiveness of the procedure is illustrated by a number of example problems of hyperelastic bodies at finite strain which experience either snap-buckling, bifurcation, or a soft load-displacement response followed by stiffening. In addition a few cases are presented to illustrate the sensitivity of the particular problems to imperfections.

Duck red cells in hypertonic media experience rapid osmotic shrinkage followed by gradual reswelling back toward their original volume. This uptake of salt and water is self limiting and demands a specific ionic composition of the external solution. Although ouabain (10(-4)M) alters the pattern of cation accumulation from predominantly potassium to sodium, it does not affect the rate of the reaction, or the total amount of salt or water taken up. To study the response without the complications of active Na-K transport, ouabain was added to most incubations. All water accumulated by the cells can be accounted for by net salt uptake. Specific external cation requirements for reswelling include: sufficient sodium (more than 23 mM), and elevated potassium (more than 7 mM). In the absence of external potassium cells lose potassium without gaining sodium and continue to shrink instead of reswelling. Adding rubidium to the potassium- free solution promotes an even greater loss of cell potassium, yet causes swelling due to a net uptake of sodium and rubidium followed by chloride. The diuretic furosemide (10(-3)M) inhibits net sodium uptake which depends on potassium (or rubidium), as well as inhibits net sodium uptake which depends on sodium. As a result, cell volume is stabilized in the presence of this drug by inhibition of shrinkage, at low, and of swelling at high external potassium. The response has a high apparent energy of activation (15-20 kcal/mol). We propose that net salt and water movements in hypertonic solutions containing ouabain are mediated by direct coupling or cis-interaction, between sodium and potassium so that the uphill movement of one is driven by the downhill movement of the other in the same direction.

A detailed description of the laboratory processing procedures for Molloplast-B-lined dentures that varies from those offered by the manufacturer has proved to be effective. 1 The processing technique for MolloplastB-lined dentures is very sensitive, consequently, no steps should be omitted. Because these procedures are time-consuming, the minimal time required is 3 full working days in the laboratory.

Chronic granulomatous disease (CGD) is usually a sex-linked recessive disorder characterized by recurrent purulent infections of the skin and lymph nodes. Affected granulocytes form diminished quantities of superoxide 1 and can ingest but not kill catalase-positive bacteria. 2 Granulocytes from patients with CGD fail to reduce nitroblue tetrazolium (NBT) to blue formazin, 3 a defect that forms the basis of tests to identify affected patients and carriers. We describe two children with CGD who had unusual symptoms in order to emphasize the variability of initial signs associated with the disease. Earlier diagnosis coupled with aggressive therapy may improve the outcome in such cases. Report of Cases .—Case1.—An 8-month-old boy was hospitalized in 1974 for evaluation of fever of one month's duration. The child was well until 6.5 months of age when right lower—lobe pneumonia developed. He was referred to The Children's Hospital of Philadelphia because of continued high

AC magnetic bridges have been used to detect applied stress in steel and aluminum test specimens. The data show effects of mechanical hysteresis. In the steel test specimens, changes in real and imaginary reluctance occur. In aluminum samples only changes in imaginary reluctance are observed. From these observations it is concluded that AC magnetic bridges can be used for the NDE of stress and could possibly be used to determine residual stress.

A 6-year retrospective investigation was conducted into the serviceability of Molloplast-B-lined dentures with the following results: The Molloplast-B-lined denture is not a temporary expedient but can remain serviceable for a time competitive with that of conventional acrylic resin dentures. All the soft liners were still serviceable after 4 years and 83% after 6 years. The longevity of the soft liner is dependent on correct processing procedures and proper home care. The three liners judged as unserviceable exhibited excessive wrinkling, and all had been soaked in a bleach-type cleanser. The resilience of the liner is dependent on its thickness. The optimum thickness is approximately 3 mm. The resilience of the liner did not decrease with time. No noticeable wear of the soft liner was observed. Staining was present in about half the soft liners. Smoking was commonly associated with staining and odor of the soft liner.

A digital computer program was developed to predict the anti-icing requirements of engine inlets by calculating water droplet trajectories toward the particular inlet through a potential flow field. The incompressible potential flow field is determined by a separate computer program using known boundary conditions. The potential flow field results are combined with the droplet and flow physical data for input to a droplet trajectory computer program. This water droplet trajectory program is based on balancing the drag, buoyancy and weight forces on the water droplet with the rate of change of the water droplet momentum. The water droplet computer program is extremely versatile because the actual design shape is used in the study and therefore the results do not need to be extrapolated.

The report was written to provide a sample problem to be used to guide the user of the water droplet impingement prediction computer program. The report is intended to illustrate the preparation of input data and the interpretation of results.

Background: Magrolimab is a humanized monoclonal antibody that blocks the immune checkpoint CD47, a "do not eat me" signal, overexpressed on tumor cells. The binding of magrolimab to CD47 leads to phagocytosis of cancer cells from human solid tumors and hematologic malignancies. The overexpression of CD47 contributes to the pathogenesis of multiple myeloma (MM) and blocking CD47 induces immediate activation of macrophages and elimination of myeloma cells (Sun et al). Hence, a blockade of CD47 with magrolimab may have therapeutic benefit in patients with MM. Combination therapies are more effective than single-agent therapy for both newly diagnosed and relapsed/refractory MM (RRMM). In vitro studies show synergy between magrolimab and daratumumab on MM cell line phagocytosis, and complimentary mechanisms suggest potential enhanced efficacy in other combinations. The current study (NCT04892446) is investigating the efficacy of magrolimab in combination with commonly used myeloma therapies in patients with RRMM. Design and Methods: This phase 2, multi-arm study includes patients aged ≥18 years currently requiring treatment for RRMM; all participants must have received at least 3 previous lines of therapy for MM, including an immunomodulatory drug and a proteasome inhibitor. This study includes 2 phases: a safety run-in cohort and a dose-expansion cohort (Figure 1). The primary objectives of the safety run-in cohort are to evaluate the safety and tolerability of magrolimab in combination with other anticancer therapies using the occurrence of dose-limiting toxicities (DLTs) as the primary endpoint, and to determine the recommended phase 2 dose (RP2D) of magrolimab in the following combinations: magrolimab+daratumumab; magrolimab+pomalidomide+dexamethasone; and magrolimab+bortezomib (maximum of 8 prior cycles in those who previously received bortezomib)+dexamethasone. Dose expansion cohorts will evaluate the efficacy of magrolimab combinations with objective response rate (ORR) as the primary endpoint. Secondary endpoints include duration of response, progression-free survival, and overall survival. Minimal residual disease negativity, biomarker changes from baseline, immune cell signaling alterations, and the mutational profile of plasma cell clones will also be explored. Magrolimab is administered intravenously (IV) with an initial priming dose, followed by a maintenance dose on days 8, 15, 22, and 29 during cycle 1 (35 days) and days 1, 8, 15, and 22 from cycle 2 (28 days) onwards. Daratumumab, pomalidomide, dexamethasone, and bortezomib will be administered according to manufacturer's prescribing information. Dose de-escalation may occur based on DLTs per protocol. Patients will continue treatment until unacceptable toxicity, progressive disease, or patient/investigator choice to discontinue. Planned enrollment is approximately 153 patients. Status: Recruitment is ongoing. Reference: Sun J, Muz B, Alhallak K, Markovic M, Gurley S, Wang Z, Guenthner N, Wasden K, Fiala M, King J, Kohnen D, Salama NN, Vij R, Azab AK. Targeting CD47 as a novel immunotherapy for multiple myeloma. Cancers (Basel). 2020;12(2):305. Figure 1 Figure 1. Disclosures Paul: Amgen Inc.: Speakers Bureau; Bristol Myers Squibb: Divested equity in a private or publicly-traded company in the past 24 months; Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees. Liedtke: Celgene: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Other: Clinical Trial Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Monge: Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Consultancy. Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Fresenius-Kabi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; McKesson: Current Employment, Current equity holder in publicly-traded company; Coherus: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb (Celgene): Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Gandhi: Karyopharm Therapeutics: Honoraria; TG Therapeutics: Honoraria; GlaxoSmithKline: Honoraria. Kovacsovics: Janssen Pharmaceuticals: Research Funding; Amgen Inc.: Research Funding; Stemline: Honoraria; Jazz Pharmaceutials: Honoraria; Novartis: Research Funding; AbbVie: Research Funding. Levy: Bristol Myers Squibb: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; GSK: Consultancy, Other: Promotional speaker; Novartis: Consultancy, Other: Promotional speaker; Amgen Inc.: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences, Inc.: Consultancy, Honoraria, Speakers Bureau; Epizyme: Consultancy, Other: Promotional speaker; Morphosys: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Janssen Pharmaceuticals: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Beigene: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Promotional speaker, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Dova: Consultancy, Other: Promotional speaker. Siegel: Karyopharm: Honoraria; Celularity: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Speakers Bureau; Takeda: Honoraria; Bristol Myers Squibb: Honoraria, Speakers Bureau; Amgen Inc.: Honoraria; Janssen: Honoraria, Speakers Bureau. Silbermann: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding. Byrne: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Ncube: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Murphy: Gilead Sciences, Inc.: Current Employment, Current holder of stock options in a privately-held company. Gu: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Rajakumaraswamy: Gilead Sciences, Inc.: Current Employment, Current equity holder in publicly-traded company. Chao: Gilead Sciences, Inc.: Current Employment; TigaTx: Membership on an entity's Board of Directors or advisory committees; Stanford University: Patents & Royalties; Hepatx Inc: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Iconovir Bio: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Stanford University Medical School: Membership on an entity's Board of Directors or advisory committees; Foresite capital: Consultancy; Bioverge: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Chimera Bioengineering: Current equity holder in publicly-traded company. Usmani: Sanofi: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; EdoPharma: Consultancy; GSK: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Array BioPharma: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy. OffLabel Disclosure: Magrolimab is an investigational therapy

Two infants who received whole blood filtered through commercially available woven stainless steel micropore filters experienced a sudden onset of hemoglobinuria. The plasma hemoglobin level in one child was 200 mg/dL. To investigate whether filters might lead to RBC destruction, we experimentally quantitated filter-induced hemolysis using standard conditions. Our studies in vitro show that hemolysis decreases with increased speed of transfusion. Hemolysis is particularly extensive with blood stored more than 14 days, but measurable hemolysis occurs with blood stored for as little as one day. (JAMA1982;248:1629-1632)

At the present time the maximum breathing capacity test provides the most significant correlation between symptoms and history of ability to work without pulmonary symptoms, as compared with the vital capacity or three-second timed vital capacity tests. As a study that can be readily performed in the general hospital or physician's office, it offers the most practicable objective guide to evaluation of dyspnea in relation to hard manual labor in coal mining. This conclusion is based on studies carried out in 482 persons, most of whom were soft-coal miners, divided into seven groups by varying degrees of breathlessness in association with physical activity. Similar studies should be done to serve as disability guides for other groups of workers.