Electronic stripe patterns near the fermi level of tetragonal Fe(Se,S).

FeSe1-xSx remains one of the most enigmatic systems of Fe-based superconductors. While much is known about the orthorhombic parent compound, FeSe, the tetragonal samples, FeSe1-xSx with x > 0.17, remain relatively unexplored. Here, we provide an in-depth investigation of the electronic states of tetragonal FeSe0.81S0.19, using scanning tunneling microscopy and spectroscopy (STM/S) measurements, supported by angle-resolved photoemission spectroscopy (ARPES) and theoretical modeling. We analyze modulations of the local density of states (LDOS) near and away from Fe vacancy defects separately and identify quasiparticle interference (QPI) signals originating from multiple regions of the Brillouin zone, including the bands at the zone corners. We also observe that QPI signals coexist with a much stronger LDOS modulation for states near the Fermi level whose period is independent of energy. Our measurements further reveal that this strong pattern appears in the STS measurements as short range stripe patterns that are locally two-fold symmetric. Since these stripe patterns coexist with four-fold symmetric QPI around Fe-vacancies, the origin of their local two-fold symmetry must be distinct from that of nematic states in orthorhombic samples. We explore several aspects related to the stripes, such as the role of S and Fe-vacancy defects, and whether they can be explained by QPI. We consider the possibility that the observed stripe patterns may represent incipient charge order correlations, similar to those observed in the cuprates.

Intrinsic electronic transitions of the absorption spectrum of (OPy)2Ti(TAP)2: implications toward photostructural modifications.

Theoretical calculations based on time-dependent density functional theory are used to characterize the electronic absorption spectrum of a heteroleptic Ti-alkoxide molecule, (OPy)(2)Ti(TAP)(2) [OPy = pyridine carbinoxide, TAP = 2,4,6 tris(dimethylamino)phenoxide] under investigation as a photosensitive precursor for use in optically initiated solution synthesis of the metal oxide. Computational results support the assignment of UV absorption features observed in solid-state precursor films to key intrinsic ground-state transitions that involve ligand-to-metal charge transfer and pi-pi* transitions within the cyclic ligand moieties present. The nature of electron density redistribution associated with these transitions provides early insight into the excitation wavelength dependence of photostructural modification previously observed in this precursor system.

Structural diversity of lithium neopentoxide compounds.

The reaction of LiN(SiMe(3))(2) with 1 equiv of HOCH(2)CMe(3) (HONep) in toluene led to the formation of [Li(mu3-ONep)](8) (1). The complex adopts a novel dual-edge fused hexagon-square prismatic structure with a C(2v) axis of rotation that relates the top and bottom eight-membered rings. Substituting the noncoordinating solvent toluene for a Lewis basic solvent (THF or py) led to the isolation of compounds of the general formula [Li(mu3)-ONep)](4)(solv)(3), where solv = THF (2) or py (3). The cube structures of 2 and 3 have one Li which is not solvated because of steric crowding of the ONep ligands. Multinuclear solid-state ((6)Li, (7)Li, and (13)C) MAS and solution-state ((1)H, (7)Li, and (13)C) NMR studies were undertaken to verify the identity of the bulk powder and to determine the solution behavior of these compounds.

203,205Tl NMR studies of crystallographically characterized thallium alkoxides. X-ray Structures of [TI(OCH2CMe3)]4 and [TI(OAr)]infinity, where OAr = OC6H3(Me)2-2,6 and OC6H3(CHMe2)2-2,6.

[Tl(OCH2Me)]4 (1) was reacted with excess HOR to prepare a series of [Tl(OR)]n, where OR = OCHMe2 (2, n = 4), OCMe3 (3, n = 4), OCH2CMe3 (4, n = 4), OC6H3(Me)2-2,6 (5, n = infinity), and OC6H3(CHMe2)2-2,6 (6, n = infinity). Single-crystal X-ray diffraction experiments revealed that in the solid state the alkoxide-ligated compound 4 adopts a cubane structure, whereas the aryloxide derivatives, 5 and 6, formed polymeric chains. Compounds 1-6 were also characterized by 203,205Tl solution and 205Tl solid-state NMR spectroscopy. In solution it was determined that 1-4 retained the [Tl-O]4 cube structure, whereas the polymeric species 5 and 6 appeared to be fluxional. Variations in the solution and solid-state structures for the [Tl(OR)]4 cubes and polymeric [Tl(OAr)]infinity are influenced by the steric hindrance of the ligand. The acidity of the parent alcohol influences the degree of covalency at the Tl metal center, which is reflected in the 203,205Tl chemical shifts for 1-6.

Effects of a kappa agonist, spiradoline mesylate (U62,066E), on activation and vaginocervical-stimulation produced analgesia in rats.

Previous research has demonstrated increased pain threshold during copulation, gestation, and parturition in animals. In the laboratory, mechanostimulation of the vaginocervical region in many animals, as well as humans, can increase responsiveness to noxious but not to innocuous stimuli. This increased pain inhibition to vaginocervical stimulation, which mimics natural parturition, is mediated by spinal and supraspinal neuropeptides, including the opiates. The present research was designed to ascertain the possible effects of a kappa opioid agonist on vaginocervical-stimulated analgesia in rats. Initially, the novel kappa-selective agonist, spiradoline mesylate (U62,066E; 0, 0.1, 1.0, 10.0 mg/kg, i.p.), was injected intraperitoneally and general behavioral arousal in an open field apparatus was recorded. Results from this experiment indicate that stimulation with the kappa-selective drug caused significant decreases in behavioral activity at the high dose as compared to saline and the medium and low doses. Next, the effects of U62,066E (0, 0.1, 1.0, 10.0 mg/kg, i.p.) on the analgesia associated with vaginocervical stimulation were determined in a tail flick apparatus. The kappa drug significantly increased antinociceptive thresholds prior to and during vaginocervical stimulation at the 0.1 and 1.0 mg/kg doses. By contrast, the high dose (10.0 mg/kg) of U62,066E decreased vaginocervical stimulation-produced analgesia. Results are discussed in terms of the potential of nonaddictive kappa-selective opioid compounds being utilized in reproductive pain.

Structural diversity in solvated lithium aryloxides. Syntheses, characterization, and structures of [Li(OAr)(THF)x]n and [Li(OAr)(py)x]2 complexes where OAr = OC6H5, OC6H4(2-Me), OC6H3(2,6-(Me))2, OC6H4(2-Pr(i)), OC6H3(2,6-Pr(i)))2, OC6h4(2-Bu(t)), OC6H3(2,6-Bu(t)))2.

A series of sterically varied aryl alcohols H-OAr [OAr = OC6H5 (OPh), OC6H4(2-Me) (oMP), OC6H3(2,6-(Me))2 (DMP), OC6H4(2-Pr(i)) (oPP), OC6H3(2,6-(Pr(i)))2 (DIP), OC6H4(2-Bu(t)) (oBP), OC6H3(2,6-(Bu(t)))2 (DBP); Me = CH3, Pr(i) = CHMe2, and Bu(t) = CMe3] were reacted with LiN(SiMe3)2 in a Lewis basic solvent [tetrahydrofuran (THF) or pyridine (py)] to generate the appropriate "Li(OAr)(solv)x". In the presence of THF, the OPh derivative was previously identified as the hexagonal prismatic complex [Li(OPh)(THF)]6; however, the structure isolated from the above route proved to be the tetranuclear species [Li(OPh)(THF)]4 (1). The other "Li(OAr)(THF)x" products isolated were characterized by single-crystal X-ray diffraction as [Li(OAr)(THF)]4 [OAr = oMP (2), DMP (3), oPP (4)], [Li(DIP)(THF)]3 (5), [Li(oBP)(THF)2]2, (6), and [Li(DBP)(THF)]2, (7). The tetranuclear species (1-4) consist of symmetric cubes of alternating tetrahedral Li and pyramidal O atoms, with terminal THF solvent molecules bound to each metal center. The trinuclear species 5 consists of a six-membered ring of alternating trigonal planar Li and bridging O atoms, with one THF solvent molecule bound to each metal center. Compound 6 possesses two Li atoms that adopt tetrahedral geometries involving two bridging oBP and two terminal THF ligands. The structure of 7 was identical to the previously reported [Li(DBP)(THF)]2 species, but different unit cell parameters were observed. Compound 7 varies from 6 in that only one solvent molecule is bound to each Li metal center of 7 because of the steric bulk of the DBP ligand. In contrast to the structurally diverse THF adducts, when py was used as the solvent, the appropriate "Li(OAr)(py)x" complexes were isolated as [Li(OAr)(py)2]2 (OAr = OPh (8), oMP (9), DMP (10), oPP (11), DIP (12), oBP (13)) and [Li(DBP)(py)]2 (14). Compounds 8-13 adopt a dinuclear, edge-shared tetrahedral complex. For 14, because of the steric crowding of the DBP ligand, only one py is coordinated, yielding a dinuclear fused trigonal planar arrangement. Two additional structure types were also characterized for the DIP ligand: [Li(DIP)(H-DIP)(py)]2 (12b) and [Li2(DIP)2(py)3] (12c). Multinuclear (6,7Li and 13C) solid-state MAS NMR spectroscopic studies indicate that the bulk powder possesses several Li environments for "transitional ligands" of the THF complexes; however, the py adducts possess only one Li environment, which is consistent with the solid-state structures. Solution NMR studies indicate that "transitional" compounds of the THF precursors display multiple species in solution whereas the py adducts display only one lithium environment.

T cells or active Epstein-Barr virus infection in the development of lymphoproliferative disease in human B cell-injected severe combined immunodeficient mice.

BACKGROUND: Severe combined immunodeficient (SCID) mice develop Epstein-Barr virus (EBV) containing human lymphoproliferative disease (LPD) tumors when reconstituted with human peripheral blood leukocytes (PBLs) from EBV-seropositive donors, but LPD tumors do not develop in the presence of immunosuppressive agents, such as cyclosporine A or corticosteroids. METHODS: Therefore, LPD development in SCID mice was used as a model to explore the relationship among B cells, T cells, and EBV in vivo. SCID mice were engrafted with PBLs isolated by leukapheresis from a single EBV-seropositive donor. Purified populations of CD3+ lymphocytes (T cells) or CD19+ lymphocytes (B cells) were isolated and engrafted into SCID mice. RESULTS: SCID mice engrafted with purified CD3+ lymphocytes (T cells) or CD19+ lymphocytes (B cells) did not develop LPD. In contrast, mice engrafted with purified B cells developed LPD if they were co-engrafted with purified T cells or if they were inoculated with infectious EBV. CONCLUSIONS: This study confirms the requirement of T cells or active EBV infection in the development of LPD in animals engrafted with B cells latently infected with EBV. A greater understanding of the cellular and viral interactions leading to transformation and malignancy may allow the development of specific interventional therapies for malignancies in the immunosuppressed host.

Phenotypic and functional consequences of herpesvirus saimiri infection of human CD8+ cytotoxic T lymphocytes.

Herpesvirus saimiri (HVS) was used to infect and transform human CD8+ cytotoxic T lymphocytes (CTL), and the phenotypic and functional consequences of HVS infection of CD8+ T lymphocytes were investigated. HVS-transformed CTL no longer require antigen restimulation yet maintain their phenotype and HLA-restricted cytolytic function and specificity. The ability of HVS to transform CTL may have an important role in the functional analysis of human antigen-specific CTL.

Adoptive transfer of cytotoxic T lymphocytes for the treatment of transplant-associated lymphoma.

BACKGROUND: Immunocompromised organ transplant recipients have a high incidence of B cell lymphomas (BCL). Severe combined immunodeficient (SCID) mice develop human BCL when engrafted with Epstein-Barr virus (EBV) transformed and immortalized B lymphoblastoid cell lines (BLCL). Because a lack of effective EBV-specific cytotoxic T lymphocytes (EBV-CTL) is thought to lead to lymphoma development, the SCID mouse model was used to determine the relationship between EBV-infected B cells and EBV-specific CTL in BCL development in vivo. METHODS: EBV-CTL were generated by in vitro stimulation of peripheral blood leukocytes with autologous BLCL. CD8+ CTL were isolated from CTL populations by depletion of CD4+ cells. SCID mice were engrafted with BLCL, EBV-CTL were adoptively transferred into engrafted SCID mice either immediately or 7 days after engraftment, and the animals were monitored for the development of BCL. Statistical significance was determined by the log rank test. RESULTS: SCID mice engrafted with BLCL rapidly developed BCL (mean, 20 days). SCID mice engrafted with BLCL and human leukocyte antigen-identical EBV-CTL or CD8+ EBV-CTL had a significant delay in BCL development (p < 0.05), whereas some mice did not develop BCL. In contrast, human leukocyte antigen-nonidentical EBV-CTL did not significantly delay BCL development. CONCLUSIONS: This study showed the role of EBV-CTL in inhibiting the development of BCL. A greater understanding of the cellular and viral interactions leading to B-cell transformation and malignancy may allow the development of specific interventional therapies in patients who have received immunosuppressants.

Retroviral gene transduction of circulating progenitor cells in patients with metastatic breast cancer.

The use of somatic gene therapy for the treatment of breast cancer has many potential applications. Because chemotherapeutic protocols for breast cancer are commonly limited by bone marrow toxicity, transduction of genes into pleuripotent stem cells may allow the generation and maintenance of immune responses in the presence of lymphocytotoxic agents. The practical utility of stem cell isolation and transduction would be enhanced if stem cells circulating in the peripheral blood could be isolated in patients, however this approach has been limited by the small numbers of such cells in the circulation. In these studies, recombinant granulocyte colony stimulating factor (G-CSF) was administered to patients with metastatic breast cancer to increase the number of circulating stem cells. Stem cells in the peripheral blood were then isolated and a retroviral vector (LXSN) was used to transduce the neomycin phosphotransferase gene into these cells. Gene transduction was demonstrated by resistance to the toxic effects of a neomycin analog (G418) and the detection of retroviral DNA from transduced cells. A practical method of transfer of exogenous genes into the circulating pleuripotent stem cells of patients with metastatic breast cancer is documented by these experiments. Application of these findings may allow the generation of cells resistant to anti-neoplastic agents or unique lymphoid effector cells with potent immune functions for the treatment of patients with metastatic breast cancer.

Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non-human primate animal model.

An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5 through the use of provocation challenges, and compared V2O5 reactivity before and after subchronic V2O5 exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5-exposed groups (n = 8 each) received equal weekly V2O5 exposures (concentration x time) with different exposure profiles. One V2O5-exposed group received 0.1 mg V2O5 m-3 on Mondays, Wednesday and Fridays, with a twice-weekly peak exposure of 1.1 mg V2O5 m-3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper-reactivity. The other V2O5-exposed group received a constant daily concentration of 0.5 mg V2O5 m-3. A control group (n = 8) received filtered, conditioned air. Pre-exposure challenges with V2O5 produced a concentration-dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5 inhalation did not produce an increase in V2O5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Stable expression of transdominant Rev protein in human T cells inhibits human immunodeficiency virus replication.

The human immunodeficiency virus (HIV) Rev protein is essential for viral structural protein expression (Gag, Pol, and Env) and, hence, for viral replication. In transient transfection assays, mutant forms of Rev have been identified that inhibit wild-type Rev activity and therefore suppress viral replication. To determine whether such transdominant Rev proteins could provide long-term protection against HIV infection without affecting T cell function, T leukemia cell lines were stably transduced with a retroviral vector encoding a transdominant mutant of the Rev protein, M10. While all the M10-expressing cell lines remained infectable by HIV-1, these same cells failed to support a productive replication cycle when infected with a cloned isolate of HIV-1. In addition, two out of three M10-expressing CEM clones were also resistant to highly productive infection by a heterogeneous HIV-1 pool. Expression of M10 did not affect induction of HIV transcription mediated by the kappa B regulatory element or Tat. Importantly, constitutive expression of Rev M10 did not alter the secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat cells. The inhibition of HIV infection in cells stably expressing a transdominant Rev protein, in the absence of any deleterious effect on T cell function, suggests that such a strategy could provide a therapeutic effect in the T lymphocytes of acquired immunodeficiency syndrome patients.

Human B-cell lymphoma in severe combined immunodeficient mice after active infection with Epstein-Barr virus.

BACKGROUND: B-cell lymphomas (BCL) occur with increased frequency in immunosuppressed patients. BCL develop in severe combined immunodeficient (SCID) mice after engraftment with human peripheral blood leukocytes (PBL; hu-PBL-SCID mice) and infection with Epstein-Barr virus (EBV). The contributions of latent and active EBV infection to BCL development, the potential enhancing effects of immunosuppressive therapy, and inhibitory effects of antiviral therapy on the development of BCL in this model were studied. METHODS: SCID mice were engrafted with PBL from EBV-seropositive donors (latent infection), PBL from EBV-seronegative donors followed by infection with EBV (active infection), PBL from EBV-seropositive donors followed by infection with EBV (latent plus active infection), or EBV-transformed B-lymphoblastoid cells and monitored for the development of BCL. Hu-PBL-SCID mice were treated with the immunosuppressive agents cyclosporine or methylprednisolone or the antiviral agents acyclovir or ganciclovir. RESULTS: Tumors developing in hu-PBL-SCID mice were high-grade lymphomas of human B-cell origin and contained EBV-DNA. BCL developed in 70% of mice 11 to 14 weeks after latent infection. BCL developed after 4 to 7 weeks in all hu-PBL-SCID mice after active infection. Treatment with cyclosporine or methylprednisolone had no effect on BCL development after active infection, but inhibited rather than enhanced the development of BCL in latently infected mice. Ganciclovir, but not acyclovir, inhibited BCL development after active infection. CONCLUSIONS: The hu-PBL-SCID mouse provides an in vivo model of BCL associated with immunosuppression. Active EBV infection results in the rapid development of BCL in this model even when latently infected B cells are present. Inhibition of BCL development in latently infected hu-PBL-SCID mice by immunosuppressive therapy may reflect inhibition of a T-cell/B-cell interaction necessary for B-cell activation. Inhibition of BCL development by granciclovir suggests a possible role for this agent in the management of BCL associated with immunosuppression.

Derivation of a biologically contained replication system for human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) proviral mutants that lack viral regulatory genes are unable to replicate unless rescued by complementation in trans. Structurally intact virus can be produced by infecting recombinant cell lines expressing the deficient genes. A HIV-1 mutant functionally defective in tat and rev (vIIIB delta Tat/Rev), which replicates only in a recombinant T-cell line expressing tat and rev (CEMTART), is described in this report. Infection of the CEMTART cell line with vIIIB delta Tat/Rev permits the complete HIV-1 life cycle, including cytopathology, decreased expression of CD4, and production of viral structural proteins, to be biologically contained. Culture supernatants from infected CEMTART contain virus that is able to replicate only in uninfected CEMTART. No reversion of vIIIB delta Tat/Rev to wild-type HIV-1 was observed as measured either by sequencing proviral vIIIB delta Tat/Rev or by detecting the ability of vIIIB delta Tat/Rev to replicate in CEM or activated CD4-bearing T lymphocytes. Defective HIV-1 mutants produced by trans complementation of essential genes permit infection and analysis of defined genotypes on cellular function and phenotype. Authentic HIV-1 structural proteins and infected cells can be prepared in mass, and agents that interfere with the HIV-1 life cycle can be studied on a large scale with minimum risk of exposing workers to virulent HIV-1.

Identification of envelope V3 loop as the major determinant of CD4 neutralization sensitivity of HIV-1.

Laboratory isolates of human immunodeficiency virus type-1 (HIV-1) such as HTLV-IIIB are generally T cell line-tropic and highly sensitive to neutralization by soluble CD4 (sCD4), a potential antiviral agent that is undergoing clinical trial. However, many primary HIV-1 isolates are macrophage-tropic and sCD4-resistant. Envelope V3 loop sequences derived from primary HIV-1 isolates were sufficient to confer on HTLV-IIIB not only the tissue tropism but also the degree of sCD4 neutralization resistance characteristic of their HIV-1 strains of origin. Single amino acid changes in the V3 loop enhanced sCD4 resistance by up to tenfold. These observations suggest that the tissue tropism and sCD4 neutralization sensitivity of HIV-1 isolates are regulated by similar mechanisms.

Effects of cyclosporine on human B-cell lymphoma development in vivo.

Cyclosporine (CsA) is a potent immunosuppressive agent primarily affecting T-lymphocyte function. Patients receive CsA following organ transplantation to prevent rejection. These patients are at high risk for developing Epstein-Barr virus (EBV)-induced lymphoproliferative disease (LPD) or B-cell lymphoma (BCL). Severe Combined Immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (PBL) develop fatal B-cell lymphomas of human origin following latent or active infection with EBV. This model was utilized to determine the role of CsA in the development of human BCL. SCID mice were reconstituted with PBL, latently or actively infected with EBV, and treated with CsA. Following active EBV infection, mice developed human BCL with or without CsA treatment. In contrast, treatment with CsA prevented the development of BCL in mice latently infected with EBV. This suggests a T-cell interaction with latently infected B-cells which is perturbed by CsA. Further understanding of this interaction and the occurrence of human BCL may allow the development of strategies to prevent, detect, or treat malignancies associated with immunosuppression.

Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1.

Cells of the monocyte-macrophage lineage are targets for human immunodeficiency virus-1 (HIV-1) infection in vivo. However, many laboratory strains of HIV-1 that efficiently infect transformed T cell lines replicate poorly in macrophages. A 20-amino acid sequence from the macrophage-tropic BaL isolate of HIV-1 was sufficient to confer macrophage tropism on HTLV-IIIB, a T cell line--tropic isolate. This small sequence element is in the V3 loop, the envelope domain that is the principal neutralizing determinant of HIV-1. Thus, the V3 loop not only serves as a target of the host immune response but is also pivotal in determining HIV-1 tissue tropism.