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Iron oxides are promising thermoelectrics, but their high electrical resistivity impedes broader applications. In this work, we have studied Fe oxides with metallic contributions. Pt and Ir additions are also considered to enhance the valence electron concentration and further modify the transport properties. Based on density functional theory explorations, Fe based clusters (Fe 3 , Fe 4 , and Fe 3 Pt) are suggested to act as nucleation sites for metallic crystallites, while O leads to formation of an amorphous matrix. This has been validated by transmission electron microscopy and x-ray photoelectron spectroscopy of sputter-grown Fe-Pt-Ir-O thin films. Densely packed bcc Fe grains, approx. 2–3 nm in diameter, are embedded in an amorphous Fe-O matrix in the as-grown state. The Seebeck coefficient reaches even −411 μV K −1 and the electrical resistivity is up to 5 orders of magnitude lower than that of previously reported literature data on Fe oxides. We suggest that this peculiarity of our films is due to finite states localized at the Fermi level in these nanocomposites.

This paper explores the fundamentals in the run-up to systemic banking crises. It applies a visualisation approach that combines elements of an event study analysis and a fan chart technique. The approach helps identify potential leading indicators. A multivariate analysis follows. This paper presents a new early warning system for banking crises built upon these indicators. The interaction of liquidity ratio and loss of demand deposits is incorporated into the model and substantially improves the results. The selected factors are highly statistically significant and robust. The out-of-sample forecasts demonstrate the strong predictive power of the model.

Universities in the United States are increasingly implementing programs to effectively respond to and manage sport-related concussions (SRC). One such effort is to develop common data elements (CDEs) and standardize data collection methods. This study aimed to describe CDEs currently collected by the Big Ten and Ivy League universities for SRCs, and to compare the collected data with the core CDEs recommended by the National Institute of Neurological Disorders and Stroke. We conducted an anonymous cross-sectional online survey among medical staff at the 22 universities (one per university). The survey instrument, including 9 questions corresponding to the concussion data collected before, during, and after a concussion, was developed and pilot-tested before field use. We analyzed patterns of the concussion CDEs being collected and compared them with the recommended core CDEs. The findings show of the 19 participating universities (participation rate of 86%), 13 were from the Big Ten and 6 from the Ivy-League. All 19 universities currently collected concussion data with athletes before, during, and after a concussion. Great similarities in data collection were observed at baseline and acutely post-concussion across participating universities. All 19 universities collected one of the ten recommended acute symptoms checklists, and 18 universities collected one of the four recommended core neuropsychological function cognitive measures. However, CDEs in the sub-acute and chronic timeframes were limited, with only 9 (47%) universities collecting short to long term post-concussion outcome data. While over 60% of participating universities collected and stored concussion data electronically, only 17% to 42% of data collected were readily available for research purposes. In conclusion, inter-institutional similarities were found in acute concussion CDEs. Further efforts should focus on collecting sub-acute and chronic timeframe core CDEs. Data access protocols should also be created to facilitate evidence-based concussion prevention and treatment for all collegiate athletes.

Background Universities are increasingly implementing programs to effectively respond to and manage sport-related concussions (SRCs). One such effort is to develop common data elements (CDEs) and standardize data collection methods. The objectives of this study were to describe CDEs currently collected by Big Ten and Ivy League universities for SRC studies, and to compare the data collected with the core CDEs recommended by the National Institute of Neurological Disorders and Stroke (NINDS). Methods We conducted an anonymous cross-sectional online survey among medical staff at the 14 Big Ten and 8 Ivy League universities (one per university) between September and October 2015. The survey instrument, including 9 questions corresponding to the concussion data collected before, during, and after a concussion, was developed and pilot-tested before field use. We analyzed patterns of the concussion CDEs being collected, including when, what, and how the data were collected and stored, and compared them with the NINDS' recommended core CDEs. Results A total of 19 out of 22 universities were included, with 13 from Big Ten and 6 from Ivy-League universities. All 19 participating universities currently collected concussion data with athletes before, during, and after a concussion. Great similarities in data collection were observed at baseline and acutely post-concussion across participating universities. All 19 universities collected at least one of the ten recommended acute symptoms checklists, and 18 universities collected one of the four recommended core neuropsychological function cognitive measures. However, CDEs in the sub-acute and chronic timeframes were limited, with only 9 (47%) universities collecting post-concussion short to long term outcome data. While over 60% of universities collected and stored concussion data electronically, only 17% to 42% of data collected were readily available for research. Conclusions Significant inter-institutional similarities in acute concussion CDEs were found. Further efforts should focus on collecting sub-acute and chronic timeframe core CDEs and creating data access protocols to facilitate evidence-based concussion prevention and treatment for all collegiate athletes.

This paper concerns the blow-up behavior of large radial solutions of polyharmonic equations with power nonlinearities and positive radial weights. Specifically, we consider radially symmetric solutions of mu = c(|x|)|u| p on an annulus {x ∈ Rn | σ ≤ |x| < ρ}, with ρ ∈ (0,∞) and σ ∈ [0, ρ), that diverge to infinity as |x| → ρ. Here n,m ∈ N, p ∈ (1,∞), and c is a positive continuous function on the interval [σ, ρ]. Letting φρ(r) := QCρ/(ρ −r)q for r ∈ [σ, ρ), with q := 2m/(p−1), Q := (q(q +1)···(q +2m−1))1/(p−1), and Cρ := c(ρ)−1/(p−1), we show that, as |x| → ρ, the ratio u(x)/φρ(|x|) remains between positive constants that depend only on m and p. Extending well-known results for the second-order problem, we prove in the fourth-order case that u(x)/φρ(|x|) → 1 as |x| → ρ and obtain precise asymptotic expansions if c is sufficiently smooth at ρ. In certain higher-order cases, we find solutions for which the ratio u(x)/φρ(|x|)does not converge, but oscillates about 1 with non-vanishing amplitude.

The PDE Δmu = u|u|p–1, with \({m\in\mathbb{N}}\) and \({p\in(1,\infty)}\), serves as a paradigm for a large class of higher-order elliptic equations with power-like nonlinearities. In studying radially symmetric solutions of this PDE and their asymptotic behavior, it is of critical importance to understand the dynamics of the associated ODE, u(2m) = u|u|p–1, which is the subject of the present paper. Most solutions of the ODE blow up in finite time, diverging to either ∞ or −∞. In the phase space \({\mathbb{R}^{2m}}\), the orbits of these two types of solutions are separated by a (2m−1)-dimensional manifold \({\fancyscript{M}}\), which is unordered and homeomorphic to each of the coordinate hyperplanes under orthogonal projection. Solutions with orbits on \({\fancyscript{M}}\) do not blow up or, else, are unbounded from above and from below (oscillatory blow-up). In the second-order case, \({\fancyscript{M}}\) coincides with the stable manifold of the trivial equilibrium. In the fourth-order case, which is our main focus, \({\fancyscript{M}}\) contains a two-dimensional manifold \({\fancyscript{M}_0}\) of periodic orbits. There exists a unique periodic solution \({\bar u}\) with \({\bar u(0)=1}\) and \({\bar u'(0)=0}\), which shares most of the symmetry properties of the common cosine; all nontrivial periodic solutions are obtained from \({\bar u}\) via scaling and phase-shifting. Every solution with orbit on \({\fancyscript{M}\setminus\fancyscript{M}_0}\) converges to either the trivial equilibrium or one of the nontrivial periodic orbits; oscillatory blow-up does not occur. In higher-order cases, the structure of the manifold \({\fancyscript{M}}\) remains largely open.

We classify the regular radial solutions of the equation Δ m u = u | u | p − 1 with m a positive integer and p ∈ ( 1 , ∞ ) . Any such solution u is uniquely determined by the center values of u and its iterated Laplacians up to order m − 1 , that is, by the “center point” ( u ( 0 ) , Δ u ( 0 ) , … , Δ m − 1 u ( 0 ) ) . Most solutions have finite exit radius (that is, they are unbounded and defined on open balls of finite radius), are eventually monotonic with respect to the radial variable, and diverge to ∞ or − ∞ . The center points of these solutions form two open half-spaces in R m , separated by an ( m − 1 ) -dimensional manifold M . Solutions with center points on M are either global, or they have finite exit radius and oscillate about 0 with unbounded amplitude. Our results yield precise information regarding the existence, multiplicity, and nature of large radial solutions of Δ m u = u | u | p − 1 on a ball of given radius.

It is well known that the biharmonic equation Δ2u=u|u|p−1 with p∈(1,∞) has positive solutions on Rn if and only if the growth of the nonlinearity is critical or supercritical. We close a gap in the existing literature by proving the existence and uniqueness, up to scaling and symmetry, of oscillatory radial solutions on Rn in the subcritical case. Analyzing the nodal properties of these solutions, we also obtain precise information about sign-changing large radial solutions and radial solutions of the Dirichlet problem on a ball.

Zusammenfassung Es wird ein nierentransplantierter Patient mit oro-pharyngo-oesophagialem Candida-Befall und Candida-Septicamie vorgestellt. Pradisponierende Faktoren fur das Auftreten der generalisierten Candidose waren ein Diabetes mellitus und die immunsuppres-sive Prednisolon-Azathioprin Therapie. Klinisch bestand eine Candida-Stomatitis, -Pharyngitis, -Oesophagitis, -Balanitis und ein massiver Candida-Befall des Verdauungsbzw. Urogenitaltraktes. Wiederholte Pilzkulturen aus Rachen, Sputum, Stuhl und Harn erbrachten den Nachweis von Candida albicans, wahrend aus dem Blut Candida para-psilosis Stamme gezuchtet wurden. Neben emsprechender Lokaltherapie mit Nystatin wurden in der Behandlung der systemischen Candidose Miconazol und 5-Fluorocytosin eingesetzt. Summary A renal transplant patient developed oro-pharyngo-oesophageal Candida infection and Candida septicaemia. Predisposing factors for the development of generalized candidiasis were diabetes mellitus and the immunosuppressive prednisolon-azathioprine therapy. Clinically Candida stomatitis, -pharyngitis, -oesophagitis, -balanitis and Candida infection of the gastrointestinal and urogenital tract were found. Candida albicans was cultured from pharynx, sputum, stool and urine. Blood cultures were positive for Candida parapsilosis. Nystatin was given locally and Miconazole and 5-fluorocytosine were chosen for treatment of the systemic candidiasis.

Substitution of Pro residues with AIB (alpha-aminoisobutyric acid) residues in peptides provides a means of evaluating the presence of cis' proline conformations both in solution and, using bioassay data, in a receptor complex. 1H n.m.r. has been used to probe the DMSO solution conformation of all seven of the possible AIB/Pro isomers of bradykinin. AIB substitution for Pro2 and/or Pro3 appears to stabilize a type III beta-turn involving the N-terminal residues, but not an incipient 3(10) helix suggested by model peptides. These substitutions are correlated with low biological potencies, suggesting that such conformational features may be incompatible with receptor complexation. Alternatively, AIB7 -bradykinin analogs exhibit a variety of long range shift perturbations relative to bradykinin. The data suggests that bradykinin can adopt several folded conformations, including beta-turns involving both Ser6-Pro7-Phe8-Arg9 and Phe5-Ser6-Pro7-Phe8. The relatively high biological activities of the AIB7-BK suggest that the complexed form of the peptide is characterized by a cis' Pro7 conformation.

We describe a novel approach to the mathematical modeling and computational simulation of fully three-dimensional, electromagnetically and thermally driven, steady liquid-metal flow. The phenomenon is governed by the Navier-Stokes equations, Maxwell’s equations, Ohm’s law, and the heat equation, all nonlinearly coupled via Lorentz and electromotive forces, buoyancy forces, and convective and dissipative heat transfer. Employing the electric current density rather than the magnetic field as the primary electromagnetic variable, it is possible to avoid artificial or highly idealized boundary conditions for electric and magnetic fields and to account exactly for the electromagnetic interaction of the fluid with the surrounding media. A finite element method based on this approach was used to simulate the flow of a metallic melt in a cylindrical container, rotating steadily in a uniform magnetic field perpendicular to the cylinder axis. Velocity, pressure, current, and potential distributions were computed and compared to theoretical predictions.

This paper is concerned with a boundary-value problem, describing the stationaryflow of a viscous, incompressible, electrically conducting fluid, confined to a bounded region of space, under mixed boundary conditions. The flow is governed by the Navier-Stokes equations, Ohm's law, and the Biot-Savart law; the boundary conditions involve the velocity field, stress tensor, electric current density, and electric potential. We derive a mixed variational formulation of the problem, which lends itself naturally to finite-element discretizations, and prove the existence and uniqueness of a (small) solution under the assumption of sufficiently small data.

An experimental technique has been developed to measure both axial and transverse velocities and temperature distribution in molten aluminum. Couette flow of liquid aluminum, lead, tin, and low melting alloy in cylindrical container was chosen for calibration of the experimental technique and the magnetic probe. Velocity and temperature profiles for liquid aluminum rotating in cylindrical container at different angular velocities are obtained for two different values of the depth. We determined that the velocity values increase with magnetic induction.

Oxidation of Bi2Te3 (space group R [Formula: see text] m) has been investigated using experimental and theoretical means. Based on calorimetry, x-ray photoelectron spectroscopy and thermodynamic modelling, Bi2Te3 is at equilibrium with Bi2O3 and TeO2, whereby the most stable compound is Bi2Te3, followed by Bi2O3. The reactivity of Bi towards oxygen is expected to be higher than that of Te. This notion is supported by density functional theory. The strongest bond is formed between Bi and Te, followed by Bi-O. This gives rise to unanticipated atomic processes. Dissociatively adsorbed oxygen diffuses through Bi and Te basal planes of Bi2Te3(0 0 0 1) and preferably interacts with Bi. The Te termination considerably retards this process. These findings may clarify conflicting literature data. Any basal plane off-cut or Bi terminations trigger oxidation, but a perfect basal cleavage, where only Te terminations are exposed to air, may be stable for a longer period of time. These results are of relevance for applications in which surfaces are of key importance, such as nanostructured Bi2Te3 thermoelectric devices.

Based on a mass-energy analysis, Nb, NbO, NbO2, NbO3, O, O2, and O3 film forming-species occur in an Nb-O2-Ar sputtering plasma. H, H2, H2O, and OH also emerge due to high-vacuum conditions. Surface diffusion pathways for fast moving species (H, O, and OH) and adsorption energy are obtained by density functional theory. H rattles, O hops in a [110] direction, and OH moves in ⟨100⟩ channels on NbO(001), while surface diffusion on NbO2(001) is not species specific. There are strongly adsorbed species (Nb, O, O2, and O3) and weakly adsorbed species (Nb-O clusters and H containing molecules). H2O, O2, and O3 dissociate, while Nb-O clusters and OH undergo nondissociative adsorption and H2 is repelled. H incorporation is thus enabled via H and OH adsorption. Nb and O seem to promote an epitaxial growth of NbO, but not of NbO2. An NbO cluster on NbO(001) and an NbO2 cluster on NbO2(001) may sustain epitaxial growth. All other Nb-O clusters lead to a growth disruption or a nanostructure formation. In general, NbO...

We are concerned with the steady flow of a conducting fluid, confined to a bounded region of space and driven by a combination of body forces, externally generated magnetic fields, and currents entering and leaving the fluid through electrodes attached to the surface. The flow is governed by the Navier--Stokes equations (in the fluid region) and Maxwell's equations (in all of space), coupled via Ohm's law and the Lorentz force. By means of the Biot--Savart law, we reduce the problem to a system of integro-differential equations in the fluid region, derive a mixed variational formulation, and prove its well-posedness under a small-data assumption. We then study the finite-element approximation of solutions (in the case of unique solvability) and establish optimal-order error estimates. Finally, an implementation of the method is described and illustrated with the results of some numerical experiments.

We derive a velocity-current formulation for the equations of stationary, incompressible magnetohydrodynamics under natural interface conditions for the magnetic field and prove its well-posedness for small data by means of a variational principle.

We study a parameter-dependent single-loop positive-feedback system in the nonnegative orthant of $\mathbb{R}^n$, with $n\in\mathbb{N}$, that arises in the analysis of the blow-up behavior of large radial solutions of polyharmonic PDEs with power nonlinearities. In Part 1 of the paper we showed that, in every dimension $n\ =12$. For $12\ =12$, followed by at least a second one if $n\>=62$, and that the number of successive bifurcations increases without bound as $n\to\infty$.

We study a parameter-dependent single-loop positive-feedback system in the nonnegative orthant of $\mathbb{R}^n$, with $n\in\mathbb{N}$, that arises in the analysis of the blow-up behavior of large radial solutions of polyharmonic PDEs with power nonlinearities. We describe the global dynamics of the system for arbitrary $n$ and prove that, in every dimension $n\ = 12$.

This paper is concerned with a weakly coupled system of quasilinear autonomous strongly parabolic equations on a compact two-dimensional manifold without boundary; the system arises from an energy balance climate model. We establish L ∞ , Hoelder, and Sobolev estimates, and apply general results on quasilinear evolution equations in order to guarantee the existence of classical nonnegative solutions. More precisely, it is shown that the system generates a global solution semiflow in the positive cone of some fractional order Sobolev space. Employing elements of the theory of infinite-dimensional dissipative systems, we prove the existence of a connected global attractor. Finally, we present some results about stationary solutions and forced periodic oscillations. The present paper extends earlier work of the authors on a semilinear problem.

Background. We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. Methods. More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. Results. Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three ...

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents.TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)).Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns.TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.

This paper is concerned with the elliptic system (0.1) Delta upsilon=phi, Delta phi=vertical bar del upsilon vertical bar(2) posed in a bounded domain Omega subset of R-N, N is an element of N. Specifically, we are interested in the existence and uniqueness or multiplicity of "large solutions," that is, classical solutions of (0.1) that approach infinity at the boundary of Omega. Assuming that Omega is a ball, we prove that the system (0.1) has a unique radially symmetric and nonnegative large solution with v(0) = 0 (obviously, v is determined only up to an additive constant). Moreover, if the space dimension N is sufficiently small, there exists exactly one additional radially symmetric large solution with v(0) = 0 (which, of course, fails to be nonnegative). We also study the asymptotic behavior of these solutions near the boundary of Omega and determine the exact blow-up rates; those are the same for all radial large solutions and independent of the space dimension. Our investigation is motivated by a problem in fluid dynamics. Under certain assumptions, the unidirectional flow of a viscous, heat-conducting fluid is governed by a pair of parabolic equations of the form (0.2) upsilon(t) -Delta upsilon=theta, theta t-Delta theta=vertical bar del upsilon vertical bar(2), where v and theta represent the fluid velocity and temperature, respectively. The system (0.1), with phi = -theta, is the stationary version of (0.2).

An experimental technique has been developed to measure the local velocity in molten metals. Couette flow of liquid aluminum, lead, tin and low melting alloy in cylindrical container was chosen for calibration of the experimental technique and the magnetic probe. Velocity and temperature profiles for liquid aluminum rotating in cylindrical container at different angular velocities are obtained for two different values of the depth. We determined that the velocity values increase with magnetic induction, and the relationship between the normalized azimuthal velocity and the magnetic induction can be expressed by quadratic function.

We describe a novel approach to the mathematical modeling and computational simulation of fully three-dimensional, electromagnetically and thermally driven liquid-metal flow. The phenomenon is governed by the Navier-Stokes equations, Maxwell’s equations, Ohm’s law, and the heat equation, all nonlinearly coupled via Lorentz and electromotive forces, buoyancy forces, and convective and dissipative heat transfer. Employing the electric current density rather than the magnetic field as the primary electromagnetic variable, it is possible to avoid artificial or highly idealized boundary conditions for electric and magnetic fields and to account exactly for the electromagnetic interaction of the fluid with the surrounding media. A finite-element method based on this approach was used to simulate the flow of a metallic melt in a cylindrical container, rotating steadily in a uniform magnetic field perpendicular to the cylinder axis. Velocity, pressure, current, and potential distributions were computed and compared to theoretical predictions.

The traditional formulation of the MHD equations employs the magnetic field as the primary electromagnetic variable. Unless the flow region is electromagnetically shielded from the surrounding space, boundary conditions are needed for the magnetic field; these can rarely be derived from physical principles. Using the current density as the primary electromagnetic variable, it is possible to avoid artificial boundary conditions and fully account for the electromagnetic interaction between flow region and surrounding space. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The flow of a viscous fluid driven by buoyancy forces is governed by balance equations for momentum, mass, and internal energy. Frequently, the Boussinesq approximation is employed to simplify the system, even in situations where dissipative heating cannot be neglected. The resulting equations violate the principle of conservation of total energy, which causes significant mathematical problems. We discuss these problems and possible remedies. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Kaposi’s sarcoma, the most common tumor occurring in human immunodeficiency virus (HIV)-infected individuals and persons with the acquired immunodeficiency syndrome (AIDS), has become a more aggressive, increasingly difficult-totreat tumor partly because of its rapid progression late in the course of AIDS.1–4 Despite significant progress in understanding and treating Kaposi’s sarcoma lesions cosmetically over the last 15 years, overall survival of patients with advanced, HIV-associated Kaposi’s sarcoma has remained unchanged,1 prompting continued research for effective and better tolerated therapies. By selectively enhancing drug delivery to tumor versus normal tissues, thereby enhancing the antitumor effects and limiting the toxicities of antineoplastic drugs, some liposomal delivery formulations have presented an exciting therapeutic advance in the treatment of advanced, HIV-associated Kaposi’s sarcoma.

This chapter explores unilamellar liposomes for anticancer, DaunoXome and antifungal, AmBisome, therapy. Visceral leishmaniasis (VL) is endemic in many areas of the world, more prevalent in areas nearer to the equator and, including the Mediterranean. AmBisome is highly effective in VL and has been approved as a first-line treatment for this disease in several countries. The direct cytotoxic effect of DaunoXome on tumors in vivo is supported by the significant reduction of tumor volume, relative to free drug. Across all free drug dose levels, each established tumor eventually grew to considerable size (>500 mg). Of 40 mice treated with DaunoXome at therapeutic doses (15–30 mg/kg), 14 had confirmed tumors that regressed and disappeared completely. This chapter highlights that the efficacy and safety of DaunoXome in the treatment of advanced AIDS-related Kaposi's sarcoma suggest that the liposomal drug will be useful for therapy of other cancers. Phase II clinical trials are underway to test DaunoXome as a single agent against lymphoma, leukemia, and solid tumors, including breast, ovarian, and brain. On the basis of the Phase III efficacy, DaunoXome has been approved for the first-line therapy of advanced AIDS-related Kaposi's sarcoma in the United States and 16 other countries.

The development of effective targeting strategies for the selective transport of boron to cancer cells has been the single most urgent problem in the area of BNCT. Successful therapy requires the site-specific delivery of relatively large amounts of boron to tumors. Strategies employed have included the use of boron compounds with some natural affinity for tumors such as 4-(dihydroxyboryl)phenylalanine (BPA)1 or B12H11SH2- ,2 the attachment of boron species to other molecules such as porphyrins,3and the conjugation of boron compounds with tumor-specific monoclonal antibodies.4 In any targeting strategy, the primary difficulties are delivering therapeutic quantities of boron, lack of specifiCity, and loss of specifiCity after incorporating useful amounts of boron in the targeting agent.

We are concerned with a parameter-dependent reaction-diffusion system on a two-dimensional compact connected oriented Riemannian manifold M without boundary (e.g., the two-sphere): $${c_j}{\partial _t}{u_j} - div\left( {{k_j}\;grad\;{u_j}} \right) = {f_j}\left( {\mu ;x,{u_1},{u_2},{u_3}} \right){\mkern 1mu} \quad \left( {j = 1,2.3} \right).$$ (*)

31P nuclear magnetic resonance (NMR) spectra of bovine platelets at 28 degrees C display prominent peaks from adenine nucleotides in two different environments, the metabolic and storage pools. Addition of 20 mM 2-deoxy-D-glucose and 0.1 mM 2,4-dinitrophenol depletes metabolic ATP, resulting in loss of nucleotide signals at 5, 10, and 19 ppm and leaving peaks at 6.5, 10.5, and 19 ppm that are assigned primarily to the dense granule storage pool. The ATP/ADP concentration ratio of the remaining pools is 1.9 +/- 0.2, with chemical shifts which reflect a more acidic environment for the intragranular nucleotides than for the cytosol. Isolated bovine dense granules give spectra with similar peak positions to those ascribed to the storage pool after metabolic depletion of whole cells. Storage pool nucleotide spectra are highly temperature dependent. Below 20 degrees C, the beta-ATP peak broadens and decreases in area to the point that it is almost undetectable at 0 degrees C, probably reflecting formation of progressively higher molecular weight aggregates at the lower temperatures. The release reaction was followed by 31P NMR after addition of thrombin at 28 degrees C. Spectra of the cell suspension taken at 5-min intervals were compared to spectra of perchloric acid extracts produced in parallel. A new finding of these experiments is that the released nucleotides rapidly undergo a transition to a "NMR silent" form as part of the bovine platelet release reacton. Metabolic breadkdown and external paramagnetic ion interactions did not explain the loss of signal from the storage pool. During release reaction, the nucleotides may be broadened out beyond detection due to immobilization by divalent cation and/or platelet membrane binding.

Methyl carbon-13 NMR spectra of purified tRNA species are presented for the first time. In addition, these spectra of tRNA species specific for phenylalanine, tyrosine, and cysteine exhibited the first resolution of single methyl carbon resonances. Carbon-13 enriched methyl groups of ribothymidine (T) and 7-methylguanosine (m7G) and the methylthio group of 2-methylthio-N6-(delta2-isopentenyl) adenosine (ms2i6A) were resolved. The T methyl signal of tRNAPhe shifted from 12.3 ppm at 45 degrees in the absence of added Mg2+ to 11.1 ppm at 30 degrees in the presence of 10mM MgCl2. The same change in conditions led to a 0.4 ppm shift of the m7G methyl signal in the opposite direction. The relative ease in obtainment of single carbon resonances of purified tRNA species, and display of the sensitivity of their chemical shifts to changes in local structure, are requisite criteria for 13C-NMR to be a useful technique in probing tRNA conformation and its changes during interaction with proteins and other nucleic acids.

The interaction of succinate with aspartate transcarbamylase from Escherichia coli has been studied by magnetic resonance relaxation measurements of the dicarboxylic acid methylene protons in H2O solutions. The pH and temperature dependence of the relaxation in the presence of either native aspartate transcarbamylase or its catalytic subunit in H2O solutions is qualitatively very similar to the corresponding situation utilizing D2O as the solvent. From previous results of measurements in D2O [C.B. Beard and P.G. Schmidt, Biochemistry 12 (1973) 22551] a mechanism was proposed involving 2 protonated groups affecting succinate binding and titratable over the pH range 7–10. Quantitatively, fitting the data from H2O solutions to the mechanism yields values of the fitting parameters generally in good agreement with the D2O experiments. The main exceptions are the pKa values calculated for the two titratable groups. For these species, the values obtained in the presence of the catalytic subunit are 6.7 and 7.8 in H2O solutions versus 7.3 and 8.6 in D2O solutions. In the presence of native enzyme the corresponding values are 6.8 and 8.3 in H2O versus 7.6 and 9.2 in D2O. These observed differences are consistent with differences in ionization constants of weak acids in D2O relative to H2O. The results imply that succinate interaction with the enzyme active site is similar in the two solvents.

Replacement of protons by deuterium at specific positions of l -malate results in simplified proton magnetic resonance spectra and a large reduction in the effect of intramolecular dipole-dipole relaxation of the proton resonances. Under conditions of concomitant deuterium decoupling, these spectra are further simplified. These advantages are used to study the proton relaxation of two specifically deuterated l -malates in the presence of the catalytic subunit of aspartate transcarbamylase. The bound relaxation rates of the deuterated L-malates are much smaller than those of undeuterated l -malate implying that the major relaxation mechanism for enzyme bound, undeuterated l -malate is the intramolecular dipole-dipole interaction.

Values of ring current shielding in parts-per-million have been calculated for double helical nucleic acids in the A-RNA (RNA-11), A' -RNA (RNA-12) and B-DNA geometries. Atomic coordinates determined previously from x-ray diffraction of fibers were used to calculate the positions of protons relative to both nearest and second nearest neighboring bases, including those on the complementary strand. The magnitude of the diamagnetic shielding was then calculated for each aromatic ring. From these calculations tables were constructed for use in determining the shielding expected for carbon-bound and ring nitrogen-bound protons of any double helical nucleic acid sequence. The results are compared with available experimental data for several oligonucleotides and with previous ring current shielding calculations where differences of up to 0.4 ppm are found.