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The conveyance of wastewater in sewer pipes can be severely limited by the growth of plant roots, which can be controlled with herbicides. However, adding herbicides in sewer lines may affect downstream biological wastewater treatment processes. The effects of three herbicides (Dithiopyr, Penoxsulam, and Triclopyr) on the mortality of cottonwood tree roots and on downstream biological nitrification were determined. The results showed that Triclopyr achieved the highest root mortality (96%) followed by Penoxsulam (77%) and Dithiopyr (75%). At concentrations used at the point of application in sewer pipes, all herbicides caused nitrification inhibition and reduction in organic carbon removal in activated sludge. However, no inhibition was observed at the more diluted concentrations approximately equal to levels that may reach the wastewater treatment facility. Overall, Triclopyr appears to be the best performing herbicide with the highest root kill., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Topological insulators are very interesting from a fundamental point of view, and their unique properties may be useful for electronic and spintronic device applications. From the point of view of applications it is important to understand the decay behavior of carriers injected in the band gap of the topological insulator, which is determined by its complex band structure (CBS). Using first-principles calculations, we investigate the dispersion and symmetry of the complex bands of Bi2Se3 family of three-dimensional topological insulators. We compare the CBS of a band insulator and a topological insulator and follow the CBS evolution in both when the spin-orbit interaction is turned on. We find significant differences in the CBS linked to the topological band structure. In particular, our results demonstrate that the evanescent states in Bi2Se3 are non-trivially complex, i.e. contain both the real and imaginary contributions. This explains quantitatively the oscillatory behavior of the band gap obtained from Bi2Se3 (0 0 0 1) slab calculations.

Realizing a large tunneling electroresistance (TER) effect is crucial for device application of ferroelectric tunnel junctions (FTJs). FTJs are typically composed of a thin ferroelectric layer sandwiched by two metallic electrodes, where TER generally results from the dependence of the effective tunneling barrier height on the ferroelectric polarization. Since the resistance depends exponentially not only on barrier height but also on barrier width, TER is expected to be greatly enhanced when one of the electrodes is a semiconductor where the depletion region near the interface can be controlled via ferroelectric polarization. To explore this possibility, we perform studies of SrRuO_{3}/BaTiO_{3}/n-SrTiO_{3} FTJs, where n-SrTiO_{3} is an electron doped SrTiO_{3} electrode, using first-principles density functional theory. Our studies reveal that, in addition to modulation of the depletion region in n-SrTiO_{3}, the BaTiO_{3} barrier layer becomes conducting near the interface for polarization pointing into n-SrTiO_{3}, leading to dramatic enhancement of TER. The effect is controlled by the band alignment between the semiconductor and the ferroelectric insulator and opens the way for experimental realization of enhanced TER in FTJs through the choice of a semiconducting electrode and interface engineering.

The relatively low magnetocrystalline anisotropy (MCA) in strongly correlated manganites (La,Sr)MnO_{3} has been a major hurdle for implementing them in spintronic applications. Here we report an unusual, giant enhancement of in-plane MCA in 6 nm La_{0.67}Sr_{0.33}MnO_{3} (LSMO) films grown on (001) SrTiO_{3} substrates when the top 2 nm is patterned into periodic stripes of 100 or 200 nm width. Planar Hall effect measurements reveal an emergent uniaxial anisotropy superimposed on one of the original biaxial easy axes for unpatterned LSMO along ⟨110⟩ directions, with a 50-fold enhanced anisotropy energy density of 5.6×10^{6}  erg/cm^{3} within the nanostripes, comparable to the value for cobalt. The magnitude and direction of the uniaxial anisotropy exclude shape anisotropy and the step edge effect as its origin. High resolution transmission electron microscopy studies reveal a nonequilibrium strain distribution and drastic suppression in the c-axis lattice constant within the nanostructures, which is the driving mechanism for the enhanced uniaxial MCA, as suggested by first-principles density functional calculations.

Symmetry protected edge states in 2D topological insulators are interesting both from the fundamental point of view as well as from the point of view of potential applications in nanoelectronics as perfectly conducting 1D channels and functional elements of circuits. Here using a simple tight-binding model and the Landauer-Büttiker formalism we explore local current distributions in a 2D topological insulator focusing on effects of non-magnetic impurities and vacancies as well as finite size effects. For an isolated edge state, we show that the local conductance decays into the bulk in an oscillatory fashion as explained by the complex band structure of the bulk topological insulator. We demonstrate that although the net conductance of the edge state is topologically protected, impurity scattering leads to intricate local current patterns. In the case of vacancies we observe vortex currents of certain chirality, originating from the scattering of current-carrying electrons into states localized at the edges of hollow regions. For finite size strips of a topological insulator we predict the formation of an oscillatory band gap in the spectrum of the edge states, the emergence of Friedel oscillations caused by an open channel for backscattering from an impurity and antiresonances in conductance when the Fermi energy matches the energy of the localized state created by an impurity.

In recent years, complex-oxide heterostructures and their interfaces have become the focus of significant research activity, primarily driven by the discovery of emerging states and functionalities that open up opportunities for the development of new oxide-based nanoelectronic devices. The highly conductive state at the interface between insulators LaAlO3 and SrTiO3 is a prime example of such emergent functionality, with potential application in high electron density transistors. In this report, we demonstrate a new paradigm for voltage-free tuning of LaAlO3/SrTiO3 (LAO/STO) interface conductivity, which involves the mechanical gating of interface conductance through stress exerted by the tip of a scanning probe microscope. The mechanical control of channel conductivity and the long retention time of the induced resistance states enable transistor functionality with zero gate voltage.

Electric-field control of spin-dependent properties has become one of the most attractive phenomena in modern materials research due to the promise of new device functionalities. One of the paradigms in this approach is to electrically toggle the spin polarization of carriers injected into a semiconductor using ferroelectric polarization as a control parameter. Using first-principles density-functional calculations, we explore the effect of ferroelectric polarization of electron-doped BaTiO3 (n-BaTiO3) on the spin-polarized transmission across the SrRuO3/n-BaTiO3(001) interface. Our study reveals that, in this system, the interface transmission is negatively spin polarized and that ferroelectric polarization reversal leads to a change in the transport spin polarization from -65% to -98%. Analytical model calculations demonstrate that this is a general effect for ferromagnetic-metal-ferroelectric-semiconductor systems and, furthermore, that ferroelectric modulation can even reverse the sign of spin polarization. The predicted effect provides a nonvolatile mechanism to electrically control spin injection in semiconductor-based spintronics devices.

Piezoresponse force microscopy imaging in conjunction with first-principles calculations provide strong evidence for room-temperature ferroelectricity in epitaxially stabilized hexagonal TbMnO3 thin films, which in the bulk form are with orthorhombic structure. The obtained results demonstrate that new phases and functional properties of complex oxide materials can be strain-engineered using epitaxial growth., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Physical and electrochemical phenomena at the surfaces of transition metal oxides and their coupling to local functionality remains one of the enigmas of condensed matter physics. Understanding the emergent physical phenomena at surfaces requires the capability to probe the local composition, map order parameter fields and establish their coupling to electronic properties. Here we demonstrate that measuring the sub-30-pm displacements of atoms from high-symmetry positions in the atomically resolved scanning tunnelling microscopy allows the physical order parameter fields to be visualized in real space on the single-atom level. Here, this local crystallographic analysis is applied to the in-situ-grown manganite surfaces. In particular, using direct bond-angle mapping we report direct observation of structural domains on manganite surfaces, and trace their origin to surface-chemistry-induced stabilization of ordered Jahn-Teller displacements. Density functional calculations provide insight into the intriguing interplay between the various degrees of freedom now resolved on the atomic level.

We explore the effect of charge carrier doping on ferroelectricity using density functional calculations and phenomenological modeling. By considering a prototypical ferroelectric material, BaTiO(3), we demonstrate that ferroelectric displacements are sustained up to the critical concentration of 0.11 electron per unit cell volume. This result is consistent with experimental observations and reveals that the ferroelectric phase and conductivity can coexist. Our investigations show that the ferroelectric instability requires only a short-range portion of the Coulomb force with an interaction range of the order of the lattice constant. These results provide a new insight into the origin of ferroelectricity in displacive ferroelectrics and open opportunities for using doped ferroelectrics in novel electronic devices.

Engineered heterostructures designed for electric control of magnetic properties, the so-called magnetoelectric interfaces, present a novel route towards using the spin degree of freedom in electronic devices. Here, we review how a subset of such interfaces, namely ferromagnet-ferroelectric heterostructures, display electronically mediated control of magnetism and, in particular, emphasis is placed on how these effects manifest themselves as detectable spin-dependent transport phenomena. Examples of these effects are given for a variety of material systems on the basis of ferroelectric oxides, manganese and ruthenium magnetic complex oxides and elemental ferromagnetic metals. Results from both theory and experiment are discussed.

We report on the density functional theory aided design of a variety of organic ferroelectric and multiferroic materials by functionalizing crystallized transition-metal molecular sandwich nanowires with chemical groups such as -F, -Cl, -CN, -NO(2), ═O, and -OH. Such functionalized polar wires exhibit molecular reorientation in response to an electric field. Ferroelectric polarizations as large as 23.0 μC/cm(2) are predicted in crystals based on fully hydroxylized sandwich nanowires. Furthermore, we find that organic nanowires formed by sandwiching transition-metal atoms in croconic and rhodizonic acids, dihydroxybenzoquinone, dichloro-dihydroxy-p-benzoquinone, or benzene decorated by -COOH groups exhibit ordered magnetic moments, leading to a multiferroic organometallic crystal. When crystallized through hydrogen bonds, the microscopic molecular reorientation translates into a switchable polarization through proton transfer. A giant interface magnetoelectric response that is orders of magnitude greater than previously reported for conventional oxide heterostructure interfaces is predicted.

Density-functional calculations are employed to investigate the effect of ferroelectric polarization of BaTiO(3) on the magnetocrystalline anisotropy of the Fe /BaTiO(3)(001) interface. It is found that the interface magnetocrystalline anisotropy energy changes from 1.33 to 1.02 erg cm (-2) when the ferroelectric polarization is reversed. This strong magnetoelectric coupling is explained in terms of the changing population of the Fe 3d orbitals at the Fe/BaTiO(3) interface driven by polarization reversal. Our results indicate that the electronically assisted magnetoelectric effects at the ferromagnetic/ferroelectric interfaces may be a viable alternative to the strain mediated coupling in related heterostructures and the electric field-induced effects on the interface magnetic anisotropy in ferromagnet/dielectric structures.

By using theoretical predictions based on first-principle calculations, we explore an interface engineering approach to stabilize polarization states in ferroelectric heterostructures with a thickness of just several nanometers., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heterostructured material systems devoid of ferroic components are presumed not to display ordering associated with ferroelectricity. In heterostructures composed of transition metal oxides, however, the disruption introduced by an interface can affect the balance of the competing interactions among electronic spins, charges and orbitals. This has led to the emergence of properties absent in the original building blocks of a heterostructure, including metallicity, magnetism and superconductivity. Here we report the discovery of ferroelectricity in artificial tri-layer superlattices consisting solely of non-ferroelectric NdMnO(3)/SrMnO(3)/LaMnO(3) layers. Ferroelectricity was observed below 40 K exhibiting strong tunability by superlattice periodicity. Furthermore, magnetoelectric coupling resulted in 150% magnetic modulation of the polarization. Density functional calculations indicate that broken space inversion symmetry and mixed valency, because of cationic asymmetry and interfacial polar discontinuity, respectively, give rise to the observed behaviour. Our results demonstrate the engineering of asymmetric layered structures with emergent ferroelectric and magnetic field tunable functions distinct from that of normal devices, for which the components are typically ferroelectrics.

First-principles density functional calculations demonstrate that a spin-polarized two-dimensional conducting state can be realized at the interface between two nonmagnetic band insulators. The (001) surface of the diamagnetic insulator FeS(2) (pyrite) supports a localized surface state deriving from Fe d orbitals near the conduction band minimum. The deposition of a few unit cells of the polar perovskite oxide LaAlO(3) leads to electron transfer into these surface bands, thereby creating a conducting interface. The occupation of these narrow bands leads to an exchange splitting between the spin subbands, yielding a highly spin-polarized conducting state distinct from the rest of the nonmagnetic, insulating bulk. Such an interface presents intriguing possibilities for spintronics applications.

A giant tunneling electroresistance effect may be achieved in a ferroelectric tunnel junction by exploiting the magnetoelectric effect at the interface between the ferroelectric barrier and a magnetic La(1-x)Sr(x)MnO3 electrode. Using first-principles density-functional theory we demonstrate that a few magnetic monolayers of La(1-x)Sr(x)MnO3 near the interface act, in response to ferroelectric polarization reversal, as an atomic-scale spin valve by filtering spin-dependent current. This produces more than an order of magnitude change in conductance, and thus constitutes a giant resistive switching effect.

Organic materials are promising for applications in spintronics due to their long spin-relaxation times in addition to their chemical flexibility and relatively low production costs. Most studies of organic materials for spintronics focus on nonpolar dielectrics or semiconductors, serving as passive elements in spin transport devices. Here, we demonstrate that employing organic ferroelectrics, such as poly(vinylidene fluoride) (PVDF), as barriers in magnetic tunnel junctions (MTJs) allows new functionality in controlling the tunneling spin polarization via the ferroelectric polarization of the barrier. Using first-principles methods based on density functional theory we investigate the spin-resolved conductance of Co/PVDF/Co and Co/PVDF/Fe/Co MTJs as model systems. We show that these tunnel junctions exhibit multiple resistance states associated with different magnetization configurations of the electrodes and ferroelectric polarization orientations of the barrier. Our results indicate that organic ferroelectrics may open a new and promising route in organic spintronics with implications for low-power electronics and nonvolatile data storage.

Importance of the Field: B-cell non-Hodgkin lymphoma (NHL) is a significant public health problem as the most common hematologic malignancy in many areas of the world. Current treatments are generally effective, but only a minority of this large group of patients can be cured., Areas Covered in This Review: Progress in clinical development of novel, targeted agents and newer cytotoxic agents has led to improved, more durable responses in all major subtypes of NHL. This article covers novel therapeutic agents, which are investigational or registered recently for NHL and/or other cancers. Subtypes of B-cell NHL are addressed separately including relevant papers over the past 20 years., What the Reader Will Gain: This review provides a better understanding of studies that have formed the basis for current treatment approaches for B-cell NHL. Also, areas of unmet need are covered. Novel agents are described along with their mechanisms of action, as well as how they might advance the treatment of B-cell NHL., Take Home Message: This review highlights advancements and the current state of knowledge by presenting clinical trial results as well as preclinical data and advances in prognostic and predictive factors that will pave the way to further progress in NHL.

Epitaxial oxide interfaces with broken translational symmetry have emerged as a central paradigm behind the novel behaviors of oxide superlattices. Here, we use scanning transmission electron microscopy to demonstrate a direct, quantitative unit-cell-by-unit-cell mapping of lattice parameters and oxygen octahedral rotations across the BiFeO3-La0.7 Sr0.3 MnO3 interface to elucidate how the change of crystal symmetry is accommodated. Combined with low-loss electron energy loss spectroscopy imaging, we demonstrate a mesoscopic antiferrodistortive phase transition near the interface in BiFeO3 and elucidate associated changes in electronic properties in a thin layer directly adjacent to the interface.

Magnetic tunnel junctions (MTJs), composed of two ferromagnetic electrodes separated by a thin insulating barrier layer, are currently used in spintronic devices, such as magnetic sensors and magnetic random access memories. Recently, driven by demonstrations of ferroelectricity at the nanoscale, thin-film ferroelectric barriers were proposed to extend the functionality of MTJs. Due to the sensitivity of conductance to the magnetization alignment of the electrodes (tunneling magnetoresistance) and the polarization orientation in the ferroelectric barrier (tunneling electroresistance), these multiferroic tunnel junctions (MFTJs) may serve as four-state resistance devices. On the basis of first-principles calculations, we demonstrate four resistance states in SrRuO(3)/BaTiO(3)/SrRuO(3) MFTJs with asymmetric interfaces. We find that the resistance of such a MFTJ is significantly changed when the electric polarization of the barrier is reversed and/or when the magnetizations of the electrodes are switched from parallel to antiparallel. These results reveal the exciting prospects of MFTJs for application as multifunctional spintronic devices.

PPARgamma is a therapeutic target that has been exploited for treatment of type II diabetes mellitus (T2DM) with agonist drugs. Since PPARgamma is expressed by many hematopoietic, mesodermal and epithelial cancers, agonist drugs were tested and shown to have both preclinical and clinical anticancer activities. While preclinical activity has been observed in many cancer types, clinical activity has been observed only in pilot and phase II trials in liposarcoma and prostate cancer. Most studies address agonist compounds, with substantially fewer reports on anticancer effects of PPARgamma antagonists. In cancer model systems, some effects of PPARgamma agonists were not inhibited by PPARgamma antagonists, suggesting noncanonical or PPARgamma-independent mechanisms. In addition, PPARgamma antagonists, such as T0070907 and GW9662, have exhibited antiproliferative effects on a broad range of hematopoietic and epithelial cell lines, usually with greater potency than agonists. Also, additive antiproliferative effects of combinations of agonist plus antagonist drugs were observed. Finally, there are preclinical in vivo data showing that antagonist compounds can be administered safely, with favorable metabolic effects as well as antitumor effects. Since PPARgamma antagonists represent a new drug class that holds promise as a broadly applicable therapeutic approach for cancer treatment, it is the subject of this review.

Tunneling anisotropic magnetoresistance (TAMR) is observed in tunnel junctions with transition metal electrodes as the moments are rotated from in-plane to out-of-plane in sufficiently large magnetic fields that the moments are nearly parallel to one another. A complex angular dependence of the tunneling resistance is found with twofold and fourfold components that vary strongly with bias voltage. Distinctly different TAMR behaviors are obtained for devices formed with highly textured crystalline MgO(001) and amorphous Al2O3 tunnel barriers. A tight-binding model shows that a fourfold angular dependence can be explained by the presence of an interface resonant state that affects the transmission of the contributing tunneling states through a spin-orbit interaction.

Peroxisome proliferator-activated receptor-gamma ligands have preclinical and clinical anticancer activity. Most studies in this area address agonists, with relatively few reports on anticancer effects of peroxisome proliferator-activated receptor-gamma antagonists. Thus, we evaluated the two pure peroxisome proliferator-activated receptor-gamma antagonists, T0070907 and GW9662, on a panel of hematopoietic and epithelial cell lines. The peroxisome proliferator-activated receptor-gamma antagonists and a reference agonist (pioglitazone) were tested in an in-vitro proliferation assay on a panel of seven hematopoietic and nine epithelial cancer cell lines, some of which are chemoresistant. Peroxisome proliferator-activated receptor-gamma expression was measured by immunoblotting, as was the effect of treatment with these agents on peroxisome proliferator-activated receptor-gamma levels. The effect of exogenous interleukin-6, an antiapoptotic cytokine, on growth inhibition was evaluated as well as the apoptotic effects of these drugs. The peroxisome proliferator-activated receptor-gamma antagonists showed significantly greater potency on all cell lines (IC50s of 3.2-29.7 versus 26.5-78.7 micromol/l for pioglitazone) and greater maximum growth inhibition. Peroxisome proliferator-activated receptor-gamma levels did not correlate with growth inhibition in this panel of cell lines. Combinations of peroxisome proliferator-activated receptor-gamma antagonists and the agonist actually showed schedule-dependent increases in growth inhibition. Exogenous interleukin-6 did not induce resistance to these agents. Both the antagonists and the agonist induced apoptosis, but only the former drugs showed caspase dependence. These two peroxisome proliferator-activated receptor-gamma antagonists have significantly more potent in-vitro antiproliferative effects versus hematopoietic and epithelial cancer cell lines. This effect does not correlate with peroxisome proliferator-activated receptor-gamma levels, suggesting alternative mechanisms or other targets of action. These findings support further translational studies to explore the mechanism of action and therapeutic potential of this class of agents.

We perform ab initio calculations of the electronic structure and conductance of atomic-size Ni nanowires with domain walls only a few atomic lattice constants wide. We show that the hybridization between noncollinear spin states leads to a reduction of the magnetic moments in the domain wall resulting in the enhancement of the domain wall resistance. Experimental studies of the magnetic moment softening may be feasible with modern techniques such as scanning tunneling spectroscopy.

Accurate and reproducible methods for the analysis of plant allelochemicals are a requirement for the study of chemical interactions between plants. This paper describes a method for sample preparation and quantitative analysis of the allelopathic chemical content of rye (Secale cereale L.) using gas chromatography (GC). Sample preparation consists of extraction of freeze-dried rye vegetative tissue with aqueous ethanol followed by partitioning of the allelochemicals into ethyl acetate, evaporation, and derivatization using the trimethylsilylating reagent N-methyl-N-trimethylsilyltrifluoroacetamide. GC analysis of the silylated mixture was performed using flame ionization detection. This method permits analysis of all known rye allelopathic agents including 2,4-dihydroxy-1,4-benzoxazin-3-one, its corresponding glucoside, 2-benzoxazolinone, beta-hydroxybutyric acid, and beta-phenyllactic acid. Identities of all compounds were confirmed by GC/MS analysis.

Published studies focused on characterizing the allelopathy-based weed suppression by rye cover crop mulch have provided varying and inconsistent estimates of weed suppression. Studies were initiated to examine several factors that could influence the weed suppressiveness of rye: kill date, cultivar, and soil fertility. Ten cultivars of rye were planted with four rates of nitrogen fertilization, and tissue from each of these treatment combinations was harvested three times during the growing season. Concentrations of a known rye allelochemical DIBOA (2,4-dihydroxy-1,4-(2H)benzoxazine-3-one) were quantified from the harvested rye tissue using high performance liquid chromatography (HPLC). Phytotoxicity observed from aqueous extracts of the harvested rye tissue correlated with the levels of DIBOA recovered in harvested tissue. The amount of DIBOA in rye tissue varied depending on harvest date and rye cultivar, but was generally lower with all cultivars when rye was harvested later in the season. However, the late maturing variety 'Wheeler' retained greater concentrations of DIBOA in comparison to other rye cultivars when harvested later in the season. The decline in DIBOA concentrations as rye matures, and the fact that many rye cultivars mature at different rates may help explain why estimates of weed suppression from allelopathic agents in rye have varied so widely in the literature.

The assessment of the degree or rate of cellular proliferation and cell viability is critical to the assessment of the effects of drugs, antibodies, or cytokines on both normal and malignant cell populations. This can be accomplished by either direct or indirect counting methods. Direct counting by manual or automated methods, using a hemacytometer or particle counter, respectively, allows for serial cell counting at multiple time points, but these are low-throughput approaches. High-throughput and robust alternatives to direct counting utilize either radiotracers (e.g., 3H-thymidine) or dye compounds, which can be adapted to multiwell culture plate formats. This chapter focuses on the use of tetrazolium-type indicator dyes, of which the compound 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) has been the most widely utilized. Newer tetrazolium dyes that yield water-soluble products and offer added flexibility, increases in sensitivity, and fewer steps, which are offset by increased costs, are also covered.

Purpose: CD74 (HLA-DR-associated invariant chain) plays a role in antigen presentation. In addition to its expression on antigen-presenting cells, it is expressed by carcinomas of renal, lung, gastric, and thymic origin and by certain sarcomas. The restricted expression of CD74 by normal tissues and its very rapid internalization make CD74 an attractive therapeutic target for both cancer and immunologic diseases. Preclinical efficacy of anti-CD74 monoclonal antibody (mAb) therapy has been demonstrated in B-lymphoma models. Because there are few validated antigenic targets in multiple myeloma, CD74 expression was examined., Experimental Design: CD74 expression was assessed by immunohistochemistry in bone marrow biopsies of known multiple myeloma cases. Its expression was measured by flow cytometry in multiple myeloma lines, and CD74 mRNA expression was determined by reverse transcription-PCR. In addition, the in vitro antiproliferative effect of LL1 mAb was evaluated on a CD74+ multiple myeloma cell line using a [3H]thymidine incorporation assay., Results: CD74 expression was observed in 19 of 22 cases of multiple myeloma, with most expressing moderate to high levels in the majority of malignant plasma cells. CD74 was expressed by most multiple myeloma cell lines, as was CD74 mRNA, at levels mirroring CD74 protein. Also, unlabeled LL1 mAb mediated in vitro growth inhibition of a CD74+ multiple myeloma cell line., Conclusions: CD74 expression is frequent in multiple myeloma, with predominant expression by the malignant plasma cells. Because anti-CD74 mAbs internalize very rapidly and LL1 mAb has shown efficacy in B-lymphoma models, CD74 represents a novel and promising target for treatment of multiple myeloma. Therefore, LL1 mAb is well suited as a carrier of radionuclides, drugs, or toxins, and also has activity as an unlabeled mAb, thereby supporting its development for this unmet need in cancer therapy.

Background: Post-mortem examinations of adults who were apparently healthy but died suddenly and unexpectedly sometimes reveal no morphological abnormalities to explain their deaths. The frequency of such unexplained deaths in relation to other causes of sudden cardiac death is not known., Aim: To estimate the frequency of sudden unexpected cardiac or unexplained death in England., Design: Prospective survey using a stratified random sample of 83 of the 132 H.M. Coroner's jurisdictions in England., Methods: Consecutive White Caucasians, aged 16-64 years, with no medical history of cardiac disease, seen alive within 12 h of death, on whom autopsy found either a cardiac or no identifiable cause of death, were included. The coroner's officer sent a copy of the post-mortem report and a completed case registration form to the investigators, with tissue samples., Results: Sixty-seven (81%) coroners participated, each maintaining prospective surveillance for 4 months. Of 692 ascertained cases, case registration forms were received for 650 (94%), post-mortem reports for 682 (99%), blood samples for 569 (82%), myocardial slices for 517 (75%) and whole hearts for 47 (7%). In cases with myocardial tissue, death was ascribed to ischaemic heart disease in 465 (82.4%). In 43.1% the ischaemia was acute, in 19.1% there was myocardial scarring but no acute ischaemia, and 20.2% had coronary atheroma only. Death was due to left ventricular hypertrophy in 32 (5.7%), to other cardiac causes in 30 (5.3%) and in 23 (4.1%) there was no clear cause. Those with cardiac causes were 81% male, median ages 55.9 (male) and 56.6 (female) years. The 23 unexplained deaths were 57% female, median ages 40.5 (male) and 54.9 (female) years. The estimated annual frequency of sudden unexpected death due to cardiac or unidentified causes, in English adults of employment age, was 11/100,000 (3481 annual deaths)., Discussion: In 4.1% of sudden unexpected deaths under 65 years, no cause was found. Until it becomes accepted practice to identify these cases by a name, such as Sudden Adult Death Syndrome (SADS), it will not be possible to study their aetiology systematically.

The Howard Hughes Medical Institute sponsored a workshop on laboratory chemical hoods on June 8, 9, and 10, 1998, that brought together 24 experts in the field of laboratory chemical hoods to critically assess the information known about hood performance. Workshop participants developed 31 consensus statements that reflect their collective views on the body of knowledge or lack thereof, for laboratory chemical hoods. The consensus statements fall into four broad categories: (1) hood selection, use, and operation; (2) hood and laboratory design issues; (3) ventilation system design issues; and (4) hood performance testing. The consensus statements include 26 statements on what is known and unknown about the performance of laboratory chemical hoods, 2 statements of definition, and 3 statements that reflect the participants' agreement not to agree. The brief commentary that follows each consensus statement provides guidance and recommendations.

Epithelial mucin-1 (MUC1) is an important target antigen that it is overexpressed in both epithelial and haematological cancers including multiple myeloma (MM) and some lymphomas and leukaemias. MUC1 has adhesive and immunosuppressive properties, which may promote cancer progression. These studies evaluated the effect of IFNs on MUC1 expression, since these agents are widely used in clinical cancer therapy. MUC1 and interferon (IFN) receptor expression were measured by radioligand binding. Changes in MUC1 mRNA levels in response to IFN-gamma were assessed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). IFN-gamma was found to be a more potent inducer of MUC1 expression than IFN-alpha. 125I-IFN binding studies indicated that both IFN receptors were expressed in most of the cell lines. With IFN-gamma treatment, there was upregulation of MUC1 mRNA. IFN-gamma has a more consistent and more potent effect upon MUC1 induction than IFN-alpha. The ability to upregulate MUC1 across a broad range of cancer types by a clinically available cytokine, IFN-gamma, has important implications for enhancing immunotherapeutic approaches targeting MUC1.

The major, minor and trace element chemistries at two freshwater tidal sites on the River Trent are described and compared with the non-tidal river, to demonstrate the variability in chemical processes in a major chemically and hydrologically active part of the river system, which is often overlooked in freshwater hydrochemical studies. The study shows a chemical gradient along which concentrations increase downstream for suspended sediments and acid-available particulate (AAP; > 0.45 microm) trace element fractions and also the 'dissolved' (< 0.45 microm) fractions of those trace elements with low-solubility phases. The study highlights the importance of tidally induced suspended-sediment dynamics and the generation of microparticulates for trace element transport within the tidal reaches. The microparticulate and particulate fractions are associated with both anthropogenic and lithogenous sources, and the concentrations of these two fractions co-vary according to a two-component mixing model involving riverine and tidal endmembers, with the tidal endmember exhibiting a strong lithogenous component. In many cases the AAP trace element concentrations are highly linearly correlated. At the downstream tidal site, suspended sediment concentrations were particularly high and ranged from 44 to over 24,000 mg/l as a result of tidally induced sediment mobilisation. As a consequence of this, particulate metal concentrations are especially high, and here, for the first time within the east coast studies of UK rivers, particulate fractions were measurable for trace elements such as boron and molybdenum, previously reported above detection limits only in dissolved form. It is demonstrated that the microparticulate components are not simply related to suspended sediment concentrations or to the bulk composition of the AAP fraction. Rather, microparticulate generation is related to a more complex pattern, probably linked to hydrodynamic factors involving sediment resuspension and microparticulate transport mechanisms.

The water quality of a major river system, the River Trent, which flows into the Humber estuary and drains large centres of population and industry in central England, is examined in terms of trace element, nutrient, major-ion, suspended sediment and carbon concentrations and set within the context of the transition from non-tidal to the tidal freshwater reaches. Detailed investigation of the water quality variability in the non-tidal river Trent has revealed mainly simple patterns in dissolved chemical concentrations, controlled largely by hydrology and the mixing of baseflow and stormflow endmember chemistries. However, silicon, carbon and nitrate show much more complex behaviour, as concentrations of these chemical determinands are regulated by in-stream biological processes. Major increases in concentrations of suspended solids and acid-available particulate (AAP) trace elements are shown to be linked to tidal mobilization of sediment and the location of the 'turbidity maximum'. Reductions in the concentrations of AAP trace elements per gram of suspended sediment suggest the mobilization of a different sediment type with a lower trace element content, which may result from: (i) a secondary sediment source; or (ii) mobilization of coarser-grained sediment under the stronger tidal hydrodynamic forces. Increased correlations for AAP-trace element interrelationships downstream suggest increasing simplicity of mixing relationships.

This paper examines spatial and temporal variability in freshwater inputs of trace elements and major ions to the tidal reaches of the River Tweed. The relationships between concentrations of major ions and trace elements (in dissolved and acid-available particulate forms) and flow are examined, and a simple two-component endmember mixing analysis performed to link river water chemistry to catchment sources, and to identify whether within-river processes modify concentrations to produce non-conservative behaviour. The results indicate that most dissolved major ions and trace elements behave conservatively in the lower reaches of the River Tweed, the variability in concentrations being dominated by hydrology and the existence of different high-flow and low-flow endmember runoff chemistries. This suggests that the variability in concentration of most dissolved trace elements and major ions in the lower Tweed can be modelled using simple mixing relationships. However, the relationships between pH, Ca, Mg and Gran alkalinity show pronounced non-conservative behaviour, indicating the importance of understanding within-river process for modelling these determinants. The non-conservative behaviour identified is related to biological controls and the resultant diurnal variations in pH which promote daytime removal of Ca from solution by precipitation of calcium carbonate (and corresponding removal of Mg by co-precipitation) during extreme low-flow conditions and algal blooms during the summer.

Interleukin-15/T(IL-15) is a growth factor that utilizes IL-2 receptor (IL-2R) components in addition to its private binding protein IL-15R(alpha) in T-cells. Here, we report that IL-15 induces mast cell proliferation in the absence of IL-2R alpha and beta. Using transfectants of these cells with a cytoplasmic-truncated mutant of gamma(c), we demonstrated that IL-15 signaling in mast cells does not involve gamma(c). Cross-linking of mast cells with [(125)I]IL-15 revealed a 60-65 kDa IL-15 binding protein that is distinct from known components of T-cell IL-15 receptors. Mast cell IL-15 receptors recruit JAK-2 and STAT-5, instead of JAK1/3 and STAT3/5 that are activated in T-cells. Thus IL-15 is a mast cell growth factor that utilizes a novel receptor and distinct signaling pathway.

We reported previously that the human T-cell lymphotrophic virus type I (HTLV-I)-associated adult T-cell leukemia line HuT-102 produces a cytokine designated interleukin (IL) T that requires interleukin (IL) 2 receptor beta-subunit expression for its action. Using anti-cytokine antibodies, we demonstrated that IL-T is identical to the simultaneously described IL-15. When compared to activated monocytes, IL-15 mRNA expression was 6- to 10-fold greater in HuT-102 cells. The predominant IL-15 message from HuT-102 is a chimeric mRNA joining a segment of the R region of the long terminal repeat of HTLV-I and the 5'-untranslated region (UTR) of IL-15. Normally, by alternative splicing, this 118-nucleotide R element represents the most 5' region of several HTLV-I transcripts including tax, rex, and env. The introduction of the R element eliminated over 200 nucleotides of the IL-15 5'-UTR, including 8 of 10 upstream AUGs that are present in normal IL-15 messages. On analysis of the 5'-UTR of normal IL-15, we demonstrated that the presence of these 10 upstream AUGs interferes with IL-15 mRNA translation. Thus, IL-15 synthesis by the adult T-cell leukemia line HuT- 102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I R element fusion message that lacks many upstream AUGs.

The Sézary syndrome (SzS) and adult T-cell leukemia (ATL) are malignant proliferations of mature T-lymphocytes that possess distinct functions. Sézary cells function as helper cells, whereas ATL cells are usually suppressor effectors. Although phenotypically similar (CD4+/CD7-/CD8-), these functional differences between the T-cell lymphoproliferative disorders suggest different patterns of cytokine expression. We wished to delineate the cytokine mechanisms potentially underlying the diverse functional characteristics of SzS and ATL. Therefore, we analyzed the expression of interleukins (IL) 2, 4, and 5, gamma-interferon, and transforming growth factor beta 1 in the highly purified leukemic T-cells from 5 SzS and 5 ATL patients. Decreased mRNA and protein levels of IL-2, gamma-interferon, and IL-5 were detected in mitogen-stimulated ATL and SzS cells when compared to similarly cultured normal CD4+ cells. In contrast, IL-4 production was markedly up-regulated in the leukemic cells of 4/5 SzS patients as compared to ATL and normal controls. Finally, fresh ATL cells secreted higher levels of transforming growth factor beta 1 into the culture medium than the malignant T-cells from SzS patients. Collectively these results suggest that, similar to the murine CD4-expressing T-cell subsets Th1 and Th2, different cytokine profiles exist in a human population of CD4+ T-cells. Moreover, the distinct patterns of IL-4 and transforming growth factor beta 1 expression by SzS and ATL cells, respectively, are most consistent with the functional differences (i.e., helper versus suppressor activity) between these T-cell malignancies and thus may play important roles in the pathogenesis of the paraneoplastic features associated with these two leukemias.

In early phases of human T-cell lymphotrophic virus I-induced adult T-cell leukemia (ATL), the malignant cell proliferation is associated with an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cells no longer produce IL-2 yet continue to express high-affinity IL-2 receptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Conditioned medium from HuT-102, when added to the IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Since CTLL-2 was purported to be IL-2-specific, we performed a number of studies to exclude IL-2 production by HuT-102. Stimulation of CTLL-2 cells by HuT-102-conditioned medium was not meaningfully inhibited by addition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells did not express mRNA encoding IL-2 as assessed by Northern blot analysis. No biological activity on CTLL-2 cells was mediated by purified IL-1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, or granulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T is a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activity of large granular lymphocytes (i.e., induced lymphokine-activated killer cells). Thus, IL-T is a lymphokine that plays a role in T-cell proliferation and induction of lymphokine-activated killer cells. Furthermore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines.