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Type 2 diabetes (T2D) is characterized by chronic insulin resistance and a progressive decline in beta-cell function. Although rigorous glucose control can reduce morbidity and mortality associated with diabetes, achieving optimal long-term glycemic control remains to be accomplished in many diabetic patients. As beta-cell mass and function inevitably decline in T2D, exogenous insulin administration is almost unavoidable as a final outcome despite the use of oral antihyperglycemic agents in many diabetic patients. Pancreatic islet cell death, but not the defect in new islet formation or beta-cell replication, has been blamed for the decrease in beta-cell mass observed in T2D patients. Thus, therapeutic approaches designed to protect islet cells from apoptosis could significantly improve the management of T2D, because of its potential to reverse diabetes not just ameliorate glycemia. Therefore, an ideal beta-cell-preserving agent is expected to protect beta cells from apoptosis and stimulate postprandial insulin secretion along with increasing beta-cell replication and/or islet neogenesis. One such potential agent, the islet endocrine neuropeptide vasoactive intestinal peptide (VIP) strongly stimulates postprandial insulin secretion. Because of its broad spectrum of biological functions such as acting as a potent anti-inflammatory factor through suppression of Th1 immune response, and induction of immune tolerance via regulatory T cells, VIP has emerged as a promising therapeutic agent for the treatment of many autoimmune diseases including diabetes. Journal of Molecular Endocrinology (2012) 49, R157-R167

Background. Clinical recognition of tularemia is essential for prompt initiation of appropriate antibiotic treatment. Although fluoroquinolones have desirable attributes as a treatment option, limited data on efficacy in the US setting exist. Methods. To define the epidemiology of tularemia in Missouri, and to evaluate practices and outcomes of tularemia management in general, we conducted a detailed retrospective review and analysis of clinical records for patients reported to the state from 2000 to 2007. Results. We reviewed records of 121 of 190 patients (64%) reported with tularemia; 79 (65%) were males; the median age was 37 years. Most patients presented with ulceroglandular (37%) and glandular (25%) forms of tularemia, followed by pneumonic (12%), typhoidal (10%), oculoglandular (3%), and oropharyngeal (2%) forms. Most cases (69%) were attributed to tick bites. Median incubation period was 3 days (range, 1–9 days), and patients sought care after a median of 3 days of illness (range, 0–44 days). Systemic disease occurred more commonly in older patients. Patients were prescribed tetracyclines (49%), aminoglycosides (47%), and fluoroquinolones (41%). Nine of 10 patients treated with ciprofloxacin for ≥10 days recovered uneventfully, without accompanying aminoglycosides or tetracyclines. Conclusions. Tularemia is frequently initially misdiagnosed. A thorough exposure history, particularly for tick bites, and awareness of clinical features may prompt clinicians to consider tularemia and facilitate appropriate testing. Promising success with oral fluoroquinolones could provide an acceptable alternative to intravenous aminoglycosides or long courses of tetracyclines where clinically appropriate.

Obesity is a mounting health concern in the United States and is associated with an increased risk for developing several cancers, including renal cell carcinoma (RCC). Despite this, little is known regarding the impact of obesity on antitumor immunity. Because dendritic cells (DC) are critical regulators of antitumor immunity, we examined the combined effects of obesity and tumor outgrowth on DC function. Using a diet-induced obesity (DIO) model, DC function was evaluated in mice bearing orthotopic RCC and in tumor-free controls. Tumor-free DIO mice had profoundly altered serum cytokine and chemokine profiles, with upregulation of 15 proteins, including IL-1α, IL-17, and LIF. Tumor-free DIO mice had elevated percentages of conventional splenic DC that were impaired in their ability to stimulate naive T cell expansion, although they were phenotypically similar to normal weight (NW) controls. In DIO mice, intrarenal RCC tumor challenge in the absence of therapy led to increased local infiltration by T cell-suppressive DC and accelerated early tumor outgrowth. Following administration of a DC-dependent immunotherapy, established RCC tumors regressed in normal weight mice. The same immunotherapy was ineffective in DIO mice and was characterized by an accumulation of regulatory DC in tumor-bearing kidneys, decreased local infiltration by IFN-γ–producing CD8 T cells, and progressive tumor outgrowth. Our results suggest that the presence of obesity as a comorbidity can impair the efficacy of DC-dependent antitumor immunotherapies.

The interaction between hexabromoethane and [CpRu(CO)2Br] (Cp = (η-C5H5), results in the deposition of two different isostoichiometric co-crystals, 2[CpRu(CO)2Br]·C2Br6, one crystallising in space group P (Z = 1) and the other in P21/n (Z = 4). These were produced in the reaction of HCBr3 and [(CpRu(CO)2)2] under indoor illumination, following a slight modification of the literature procedure. The origin of the hexabromoethane is as yet unknown but it appears to have been formed in the reaction rather than being an impurity in the bromoform. We have analysed the structures using the Hirshfeld surface approach and electrostatic potentials, supported by DFT theoretical calculations to better define the nature of intermolecular interactions in the solid state. The results indicate that the most significant interactions within both crystal forms arise not from the closest van der Waals contacts but, rather, from more distant interactions between the unsymmetrical electron distributions about the bromine atoms in the solvate and substrate molecules.

Single crystal X-ray studies are presented for the ‘piano-stool’ structures [CpRu,Os(CO)2Cl], [Cp′Ru(CO)2X] (X = Cl, Br, I (redetermination)), [Cp*Ru(CO)2Cl] (two phases), enabling the assembly of comparative geometric data for the [CpM(CO)2Cl] (M = Fe, Ru, Os), [Cp,Cp′Ru(CO)2X] (X = Cl, Br, I) and [CpxRu(CO)2Cl] (Cpx = Cp (η–C5H5), Cp′ (η–C5H4CH3), Cp* (η–C5CH3)5,CpPh (η–C5(C6H5)5)). In the [Cp′Ru(CO)2X] arrays, the methyl groups are found to consistently lie ‘eclipsed’ vis-a-vis the halogen substituents, with a concomitant tilt of the Cp ring; the reasons for this are explored theoretically.

Regulatory T cells (Tregs) can suppress a wide variety of cell types, in diverse organ sites and inflammatory conditions. Whereas Tregs possess multiple suppressive mechanisms, the number required for maximal function is unclear. Furthermore, whether any interrelationship or cross-regulatory mechanisms exist to orchestrate and control their utilization is unknown. In this study, we assessed the functional capacity of Tregs lacking the ability to secrete both IL-10 and IL-35, which individually are required for maximal Treg activity. Surprisingly, IL-10/IL-35 double-deficient Tregs were fully functional in vitro and in vivo. Loss of IL-10 and IL-35 was compensated for by a concurrent increase in cathepsin E (Ctse) expression, enhanced TRAIL (Tnfsf10) expression, and soluble TRAIL release, rendering IL-10/IL-35 double-deficient Tregs functionally dependent on TRAIL in vitro and in vivo. Lastly, whereas C57BL/6 Tregs are normally IL-10/IL-35 dependent, BALB/c Tregs, which express high levels of cathepsin E and enhanced TRAIL expression, are partially TRAIL dependent by default. These data reveal that cross-regulatory pathways exist that control the utilization of suppressive mechanisms, thereby providing Treg functional plasticity.

An immune response of appropriate magnitude should be robust enough to control pathogen spread but not simultaneously lead to immunopathology. Primary infection with influenza A virus (IAV) results in a localized pulmonary infection and inflammation and elicits an IAV-specific CD8 T cell immune response necessary for viral clearance. Clearance of IAV-infected cells, and recovery from infection, is mediated by perforin/granzyme B- and Fas/FasL-mediated mechanisms. We recently reported that TRAIL is another means by which IAV-specific CD8 T cells can kill IAV-infected cells. The current study examined the role of TRAIL in the pulmonary CD8 T cell response to a clinically significant IAV [A/PR/8/34 (PR8; H1N1)] infection (i.e., leads to observable, but limited, morbidity and mortality in wild-type [WT] mice). Compared with WT mice, IAV-infected Trail−/− mice experienced increased morbidity and mortality despite similar rates of viral clearance from the lungs. The increased morbidity and mortality in Trail−/− mice correlated with increased pulmonary pathology and inflammatory chemokine production. Analysis of lung-infiltrating lymphocytes revealed increased numbers of IAV-specific CD8 T cells in infected Trail−/− mice, which correlated with increased pulmonary cytotoxic activity and increased pulmonary expression of MIG and MIP-1α. In addition, there was decreased apoptosis and increased proliferation of IAV-specific CD8 T cells in the lungs of Trail−/− mice compared with WT mice. Together, these data suggest that TRAIL regulates the magnitude of the IAV-specific CD8 T cell response during a clinically significant IAV infection to decrease the chance for infection-induced immunopathology.

The mammalian immune system continually faces death in the form of its own dead and dying cells that arise during normal tissue turnover, infections, cellular damage, and cancer. Complex decisions must then be made that will permit a protective response to pathogens, while at the same time destroying tumors but not attacking vital systems of the host that could lead to autoimmunity. By using an investigative technique termed the five Ws (who, what, when, where, and why), we will examine how the immune system responds to antigens generated via cell death. This analysis will give us a better understanding of the molecular differences fundamental to tolerogenic or immunogenic cell death, the cells that sense and react to the dead cells, and the consequences of these fundamental elements on the maintenance or abrogation of tolerance.

Sepsis is the leading cause of death in most intensive care units, and patients who survive the hyperinflammation that develops early during sepsis later display severely compromised immunity. Not only is there apoptosis of lymphoid and myeloid cells during sepsis that depletes these critical cellular components of the immune system, but also the remaining immune cells show decreased function. Using a cecal-ligation and puncture (CLP) model to induce intra-abdominal polymicrobial peritonitis, we recently established a link between the apoptotic cells generated during sepsis and induction of sepsis-induced suppression of delayed-type hypersensitivity. The present study extends this earlier work to include a secondary heterologous bacterial infection (OVA257-expressing Listeria monocytogenes [LM-OVA]) subsequent to sepsis initiation to investigate sepsis-induced alterations in the control of this secondary infection and the associated naive Ag-specific CD8 T cell response. We found that CLP-treated wild-type (WT) mice had a reduced ability to control the LM-OVA infection, which was paralleled by suppressed T cell responses, versus sham-treated WT mice. In contrast, CLP-treated Trail−/− and Dr5−/− mice were better able to control the secondary bacterial infection, and the Ag-specific CD8 T cell response was similar to that seen in sham-treated mice. Importantly, administration of a blocking anti-TRAIL mAb to CLP-treated WT mice was able to restore the ability to control the LM-OVA infection and generate Ag-specific CD8 T cell responses like those seen in sham-treated mice. These data further implicate TRAIL-dependent immune suppression during sepsis and suggest TRAIL neutralization may be a potential therapeutic target to restore cellular immunity in septic patients.

Understanding how linear strings fold into 2-D and 3-D shapes has been a long sought goal in many fields of both academia and industry. This paper presents a technique to design self-assembling and self-reconfigurable systems that are composed of strings of very simple robotic modules. We show that physical strings that are composed of a small set of discrete polygonal or polyhedral modules can be used to programmatically generate any continuous area or volumetric shape. These modules can have one or two degrees of freedom (DOFs) and simple actuators with only two or three states. We describe a subdivision algorithm to produce universal polygonal and polyhedral string folding schemas, and we prove the existence of a continuous motion to reach any such folding. This technique is validated with dynamics simulations as well as experiments with chains of modules that pack on a regular cubic lattice. We call robotic programmable universally foldable strings “moteins” as motorized proteins.

SUMMARYPlague is thought to have killed millions during three catastrophic pandemics. Primary pneumonic plague, the most severe form of the disease, is transmissible from person-to-person and has the potential for propagating epidemics. Efforts to quantify its transmission potential have relied on published data from large outbreaks, an approach that artificially inflates the basic reproductive number (R0) and skews the distribution of individual infectiousness. Using data for all primary pneumonic plague cases reported in the USA from 1900 to 2009, we determined that the majority of cases will fail to transmit, even in the absence of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained outbreaks still exists due to superspreading events. These findings challenge current concepts regarding primary pneumonic plague transmission.

Multistate start-up demonstration tests are proposed and analyzed using a Markov Chain approach. The new demonstration tests are generalizations of the CSTF, TSTF, and CSCF start-up demonstration tests discussed in the literature that have the important practical advantage of allowing for early termination when the quality of successful start-ups is exceptional. When the termination results in acceptance of the equipment, the use of a multi-state startup demonstration test results in an increase in the probability of an early termination of as much as. 35 over the optimal binary start-up test in cases studied. The Markov Chains methodology is used in the probabilistic analysis. Practical guidance on choosing tests, estimation, and comparisons of the various criteria are studied. The Markov Chain approach is then extended to study the non-i.i.d. case.

Systemic immunological tolerance to Ag encountered in the eye restricts the formation of potentially damaging immune responses that would otherwise be initiated at other anatomical locations. We previously demonstrated that tolerance to Ag administered via the anterior chamber (AC) of the eye required Fas ligand-mediated apoptotic death of inflammatory cells that enter the eye in response to the antigenic challenge. Moreover, the systemic tolerance induced after AC injection of Ag was mediated by CD8+ regulatory T cells. This study examined the mechanism by which these CD8+ regulatory T cells mediate tolerance after AC injection of Ag. AC injection of Ag did not prime CD4+ T cells and led to increased TRAIL expression by splenic CD8+ T cells. Unlike wild-type mice, Trail−/− or Dr5−/− mice did not develop tolerance to Ag injected into the eye, even though responding lymphocytes underwent apoptosis in the AC of the eyes of these mice. CD8+ T cells from Trail−/− mice that were first injected via the AC with Ag were unable to transfer tolerance to naive recipient wild-type mice, but CD8+ T cells from AC-injected wild-type or Dr5−/− mice could transfer tolerance. Importantly, the transferred wild-type (Trail+/+) CD8+ T cells were also able to decrease the number of infiltrating inflammatory cells into the eye; however, Trail−/− CD8+ T cells were unable to limit the inflammatory cell ingress. Together, our data suggest that “helpless” CD8+ regulatory T cells generated after AC injection of Ag enforce systemic tolerance in a TRAIL-dependent manner to inhibit inflammation in the eye.

Previous research has indicated that the blockade of H(3)-type histamine receptors may improve attention and memory in normal rodents. The purpose of this study was to determine if ciproxifan, an H(3) receptor antagonist, could alleviate the hyperactivity and cognitive deficits observed in a transgenic mouse model (APP(Tg2576)) of Alzheimer's disease. APP(Tg2576) mice displayed significantly greater locomotor activity than wild-type mice, but APP(Tg2576) mice provided with daily ciproxifan treatment showed activity levels that did not differ from wild-type mice. In the swim maze, APP(Tg2576) mice exhibited significantly longer escape latencies, but the APP(Tg2576) mice treated daily with ciproxifan had latencies that were indistinguishable from controls. In probe trials conducted one hour after the last training trial, ciproxifan-treated APP(Tg2576) mice spent more time near the previous platform location and made more crossings of this area than did saline-treated APP(Tg2576) mice. APP(Tg2576) mice also demonstrated a significant impairment in the object recognition task that was reversed by acute treatment with ciproxifan (3.0mg/kg). These data support the idea that modulation of H(3) receptors represents a novel and viable therapeutic strategy in the treatment of Alzheimer's disease.

Lyme disease was listed as an underlying or multiple cause of death on 114 death records during 1999-2003. Upon review, only 1 record was consistent with clinical manifestations of Lyme disease. This analysis indicates that Lyme disease is rare as a cause of death in the United States.

Background. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a death ligand currently under clinical trials for cancer. The molecular profile of TRAIL and TRAIL receptors has not yet been mapped for patients with laryngeal squamous cell carcinoma (SCC) or patients with oral cavity squamous cell carcinoma (OCSCC). Methods. Paraffin-embedded tissues from 60 patients with laryngeal SCC and 14 patients with OCSCC were retrospectively analyzed using immunohistochemistry. Results. An increase in decoy-R1 (DcR1) but a decrease in decoy-R2 (DcR2) expression were observed in patients with laryngeal SCC and in patients with OCSCC compared with control individuals with benign lesions. Clinical and pathologic grading revealed distinctive TRAIL and TRAIL receptor profiles in patients with squamous cell carcinoma of the head and neck (SCCHN). Conclusions. TRAIL and a TRAIL receptor expression profile might be useful to follow-up disease progression by virtue of its connection with clinical staging and pathologic grading in patients with laryngeal SCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010

Introduction Combination of tumor-associated antigen (TAA) and toll-like receptor (TLR) agonists can facilitate a potent anticancer immune response. Synthetic peptides, which are derived from antigens that are highly elevated or only expressed in tumor tissue, have been investigated as a source of TAA. However, these peptides are not available for all tumor types and often poorly immunogenic. Whole tumor cell lysate is a promising alternate antigen source that seeks to overcome some of the limitations associated with peptide-based vaccines. In this study, we utilized whole tumor cell lysate as antigen source and a novel TLR 7/8 agonist encapsulating nanoparticles as adjuvant to formulate the cancer vaccine and examined its efficacy against subcutaneous (S.C.) tumor models. Methods A new imidazaquinoline-based TLR 7/8 agonist (termed ‘522') was encapsulated in poly(lactide-co-glycolide) (PLGA) nanoparticles using emulsion solvent evaporation method to formulate the vaccine adjuvant. The adjuvant (522NP) was used in combination with whole tumor cell lysate (CL) prepared from murine bladder carcinoma (MB49) cells. Immunocompetent C57BL/6 mice were immunized subcutaneously with 5 doses of cell-lysate vaccine or various control treatments. Two days after the final vaccination dose, mice were sacrificed and organs were harvested. Splenocytes were analyzed using flow cytometry to measure antigen (Ag)-specific CD8 T cell response. We investigated whether prophylactic and therapeutic CL+522NP immunization can delay tumor growth and improve survival in MB49 S.C. tumor models. Results CD11ahighCD8low CD8 T cells were examined as they represent Ag-experienced CD8 T cells that can respond to Ag. Frequency of CD11ahigh CD8low CD8 T cells increased in mice vaccinated with CL+522NP. In the prophylactic model, CL+522NP significantly delayed tumor growth compared to that in other control groups. On d 30, average tumor volumes reached ~1000 mm3 in untreated mice compared to ~500 mm3 in CL alone and CL+Soluble522 treated groups. However, CL+522NP vaccinated mice showed remarkably very little tumor growth (~122 mm3) over the same time period. In the therapeutic model, only CL+522NP treatment was effective in delaying tumor growth. Unlike in the prophylactic study, where CL alone had a moderate effect, therapeutic effects were not observed from CL alone or CL+Soluble522 groups. Conclusion CL+522NPs vaccination triggered a robust anti-cancer immune response that resulted in the expansion of CD11ahigh CD8low CD8 T cells, which suggests that 522NPs enhance the immunogenicity of cell lysate and elicit Ag-specific CD8 T cell response. Furthermore, CD8 T cells generated by CL+522NPs vaccination appeared to be effective in killing tumors in both prophylactic and therapeutic tumor models. These results suggest that 522NPs are effective vaccine adjuvants capable of improving the outcome of cancer immunotherapy. Citation Format: Hyunjoon Kim, Peter Larson, Tamara A. Kucaba, Katherine A. Murphy, David M. Ferguson, Thomas S. Griffith, Jayanth Panyam. Nanoparticle-based tumor cell lysate vaccine for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 718.

Synchrotron X-ray diffraction and neutron diffraction have been used to investigate the phase changes that the titanosilicate mineral sitinakite undergoes when dehydrated. Refinements of the powder diffraction data of the material before and after heating to 573K indicate a phase change from space group P42/mcm to P42/mbc. Upon exposure to normal atmospheric conditions for an extended period the material transforms back to P42/mcm with a reduced lattice parameter. If the material is heated in a sealed capillary, it is possible to get the two phases coexisting. The coexistence of these two phases in sealed system suggests that it is only the loss of H2O that is driving the reversible phase transformation.

Patients who survive severe sepsis often display severely compromised immune function. One hallmark of such immune suppression in septic patients is an impaired delayed-type hypersensitivity (DTH) response, manifested by a loss of skin testing to recall Ags. Because sepsis induces significant apoptosis in lymphoid and myeloid cells, and apoptotic cells are themselves tolerogenic, we tested the hypothesis that suppression of DTH is mediated by tolerogenic properties of the apoptotic cells generated during sepsis. Mice subjected to cecal ligation and puncture demonstrated a loss of DTH for the 7 d following cecal ligation and puncture; however, the immune response returned to normal by day 10. Blocking sepsis-induced apoptosis via Bcl-2 overexpression or Bim deficiency prevented the loss of DTH. Importantly, injection of apoptotic cells into Bim−/− mice prevented an effective DTH response, thereby suggesting a causal link between apoptotic cells and immune suppression. Surprisingly, when TRAIL null mice were examined, we found that these animals had significant apoptosis but retained their DTH responses. Further studies revealed that apoptotic cells generated during sepsis induced a CD8+ regulatory T cell that suppressed DTH by TRAIL production. These results establish a link between apoptotic cells and immune suppression during sepsis and suggest TRAIL may be a viable therapeutic target for boosting the adaptive immune response following sepsis.

The evaporation-induced self-assembly of mesoporous zirconium titanium oxide thin films prepared from precursor solutions with the composition ZrxTi1−xCl4:40 EtOH:0.005 Brij 58:h H2O (where x = 0.28, h = 10, and Brij 58 = diblock copolymer C16H33PEO20) by dip coating has been studied as a function of the mole fraction of zirconium (x), the relative humidity (RH), and the drying conditions. Extremely well-ordered mesophases and compositional homogeneity on the atomic scale were consistently obtained when the films were prepared at relative humidities above 60%, under which conditions a cubic phase was identified. The influence of humidity was monitored using a combination of in situ small-angle X-ray diffraction (SAXD) and small-angle X-ray scattering (SAXS). These techniques showed the existence of nanocrystalline phases during the initial drying process for films prepared from precursor solutions with x in the range of 0.20−0.60. The nanocrystalline phases were evidenced as multiple X-ray reflections abo...

From September through early December 2005, an outbreak of yellow fever (YF) occurred in South Kordofan, Sudan, resulting in a mass YF vaccination campaign. In late December 2005, we conducted a serosurvey to assess YF vaccine coverage and to better define the epidemiology of the outbreak in an index village. Of 552 persons enrolled, 95% reported recent YF vaccination, and 25% reported febrile illness during the outbreak period: 13% reported YF-like illness, 4% reported severe YF-like illness, and 12% reported chikungunya-like illness. Of 87 persons who provided blood samples, all had positive YF serologic results, including three who had never been vaccinated. There was also serologic evidence of recent or prior chikungunya virus, dengue virus, West Nile virus, and Sindbis virus infections. These results indicate that YF virus and chikungunya virus contributed to the outbreak. The high prevalence of YF antibody among vaccinees indicates that vaccination was effectively implemented in this remotely located population.

Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) regulates cellular apoptosis and inflammation, and growing evidence indicates a key role in antiviral defense. Cytomegalovirus (CMV, a b-herpesvirus) establishes a lifelong persistent/latent infection that depends upon viral subversion of host innate and adaptive defenses. We have shown that both human and mouse CMV inhibit signaling by the TRAIL death receptors (DR) through the use of specific viral proteins. MCMV m166 blocks TRAIL-DR expression and promotes early viral replication by evading TRAIL-mediated natural killer (NK) cell defenses. After one week of systemic replication, MCMV spreads to the salivary glands (SG), the major mucosal organ responsible for horizontal transmission of the virus. We show that a MCMVΔm166 mutant replicates at lower absolute levels in the SG, but, surprisingly, persists for much longer times. Recent evidence suggests a role of type 1 Innate Lymphoid cells (ILC1) in control/clearance of MCMV. We investigated the role of the 2 main ILC1 populations (conventional and tissue resident (tr) NK cells) in controlling MCMV SG persistence. Depleting ILC1 prior to infection, or infection of TRAIL−/− mice, restored MCMVΔm166 SG replication to normal levels. In addition, SG trNK cells display a unique phenotype and express high levels of TRAIL during MCMV infection when compared to their conventional counterparts. Together our data reveal a key role for m166 inhibition of TRAIL-DR expression in promoting viral persistence by blocking ILC1 effector functions mediated by TRAIL, highlighting this TNF-family cytokine as an important factor regulating innate defenses in mucosal tissues.

This study investigates the structural evolution of a series of nanohybrid powders and coatings synthesized by direct co-condensation of amino-functionalized alkyltrialkoxysilanes and tetraalkoxysilanes with an aromatic carboxylic acid (trimesic acid, TMA) as a structure directing agent. Fourier transform infrared spectroscopy (FTIR) and (13)C CP-MAS NMR results have suggested the formation of secondary (-CO-NH-) amide linkages upon interaction of TMA with the amino functionalized silane thus creating a "scaffold" around which the silica network is formed and also assisting in more homogeneous distribution of nitrogen sites within the nanohybrid structure. Functionalized silica powders were investigated for their potential to remove toxic oxyanions from mildly acidic or basic solutions. The uptake of Mo(VI), Se(VI), and Cr(VI) oxyanions was investigated as a function of the nanohybrid composition, oxyanion concentration, and solution pH using laser diffraction particle sizing, gas adsorption, and various spectroscopic techniques. The adsorption data obtained for Mo and Se could be adequately described by Langmuir adsorption isotherms, while the Freundlich isotherm is employed to fit the adsorption data for Cr. An easily accessible processing window (of pH, aging time, etc.) has been identified allowing production of continuous and uniform thin nanohybrid coatings on silicon and glass substrates. These coatings were tested as chemical barriers against Mo leaching from specially prepared Mo-doped glass. Leaching studies were conducted over 200 days in water at 90 degrees C and the Mo leaching from coated and uncoated samples compared.

The HOMINIDS ABM is a new Agent Based Model that simulates the actions of two species of proto-human agents defined by a few, simple parameters. These proto-human agents attempt to subsist by foraging and nesting on dynamic, spatially explicit landscapes. The landscapes are described with a number of parameters based on empirical field data collected in habitats in East Africa. The results of three separate scenarios with 1 year model runs repeated 30 times each, for a total of 90 simulations, are presented and discussed to illustrate both the capacity and flexibility of our ABM modeling environment. The simulations show that the model food preferences and anatomy ascribed to Australopithecus boisei resulted in different expressions of foraging behaviors and subsistence strategies in two distinct ecological settings, and that adding tubers to the diet significantly increases the chances of the hominid agents meeting their daily caloric requirements year-round. In addition, this paper provides links to the open-source implementation code, along with the user documentation, design document, java API, and all datasets required to replicate the simulations.

Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

The decision to generate a productive immune response or tolerance often depends on the context in which T cells first see Ag. Using a classical system of tolerance induction, we examined the immunological consequence of Ag encountered in the presence of naive or activated apoptotic cells. Naive apoptotic cells induced tolerance when injected i.v.; however, previously activated apoptotic cells induced immunity. Further analysis revealed a key role for CD154, as tolerance resulted after i.v. injection of either naive or activated apoptotic CD154−/− T cells, while coinjection of an agonistic anti-CD40 mAb with naive apoptotic T cells induced robust immunity. Dendritic cells fed activated apoptotic T cells in vitro produced IL-12p40 in a CD154-dependent manner, and the use of IL-12p40−/− mice or mAb-mediated neutralization of IL-12 revealed a link between CD154, IL-12, and the ability of activated apoptotic T cells to induce immunity rather than tolerance. Collectively, these results show that CD154 expression on apoptotic T cells can determine the outcome of an immune response to Ag recognized within the context of the apoptotic cells and suggest that the balance between naive and activated apoptotic T cells may dictate whether a productive immune response is encouraged.

We tested a new light detection cooled charge-coupled device (CCD) for in vivo assessment of noninvasive, whole-body fluorescence optical imaging of adenovirus directed enhanced green fluorescent protein (AdEGFP) expression. AdEGFP was injected i.v. into BALB/c mice via tail vein. Whole-body fluorescence optical imaging of AdEGFP expression was performed using a Kodak 2000MM Image Station before and after vector administration. EGFP expression was exclusively detected around the abdominal cavity, and the fluorescent signal peaked at day 4 and then remained detectable for at least 30 days. Ex vivo fluorescence imaging confirmed that EGFP expression was restricted to the liver, and transgene expression was homogeneously diffused into all four lobes. These findings demonstrate that in vivo fluorescence imaging provides functional data indicating the approximate location, magnitude, and duration of AdEGFP expression.

Recent studies have raised the possibility that antagonists of H(3) histamine receptors possess cognitive-enhancing and antipsychotic properties. However, little work has assessed these compounds in classic animal models of schizophrenia.The purpose of this study was to determine if a prototypical H(3) antagonist, thioperamide, could alter behavioral deficits caused by the N-methyl-D: -aspartate (NMDA) receptor antagonist, MK-801, in adult male rats. MK-801 was chosen to be studied since it produces a state of NMDA receptor hypofunction in rats that may be analogous to the one hypothesized to occur in schizophrenia.The interaction between thioperamide and MK-801 was measured in three behavioral tests: locomotor activity, prepulse inhibition (PPI), and delayed spatial alternation. In each test, rats received a subcutaneous injection of saline or thioperamide (3.0 and 10 mg/kg) followed 20 min later by a subcutaneous injection of saline or MK-801 (0.05, 0.10, and 0.30 mg/kg).Locomotor activity was significantly elevated by MK-801 in a dose-dependent manner. Thioperamide pretreatment alone did not alter locomotor activity; however, its impact on MK-801 was dose-dependent. Each thioperamide dose enhanced the effects of two lower doses of MK-801 but reduced the effect of a higher MK-801 dose. Clear deficits in PPI and delayed spatial alternation were produced by MK-801 treatment, but neither impairment was significantly modified by thioperamide pretreatment.H(3) receptors modulate responses to NMDA antagonists in behaviorally specific and dose-dependent ways.

We evaluated a biodegradable graft for reconstruction of rat vasa deferentia with long obstructed or missing segments. A total of 47 Sprague-Dawley rats underwent bilateral vasectomy and were divided into groups according to length of the vas deferens affected (0.5, 1, 1.5 cm). After 8 weeks, poly-(D,L-lactide) (PDLA) grafts were used to reconnect the vas deferens. Grafts and adjoining vasa deferentia were excised 8 and 12 weeks later and evaluated microscopically. At 8 weeks, microscopic changes included a robust inflammatory response around the grafts. All grafts were still intact but in the early stages of degradation. No microtubules, indicative of vas deferens recanalization, were identified. One specimen showed evidence of healing and neovascularization at the interface zone between the vas deferens and the graft. At 12 weeks, grafts were further degraded but still present. Microscopic evaluation showed decreased inflammation. Seven specimens showed neovascularization at the interface zone; two of these showed distinct epithelialized vas deferens microcanals at the graft edges. One specimen showed a microcanal spanning the entire 0.5-cm graft. A time period of 8 weeks is not ample enough for vas deferens regeneration in the setting of a biodegradable PDLA graft; however, early evidence of re-growth was seen at 12 weeks. A longer healing time should permit further biodegradation of the graft, as well as re-growth and possible eventual reconnection of the vas deferens, allowing passage of sperm. These findings suggest a potential role for biodegradable grafts in the reconstruction of vas deferens with long obstructed segments.

A novel two-step solution phase protocol for the synthesis of arrays of triazadibenzoazulenones is reported. The methodology employs the Ugi reaction to assemble desired diversity and acid treatment enables two tandem ring closing transformations. The order of ring closure is shown to be key for optimal conversion to the desired tetra-cyclic product and initially proceeds through a benzimidazole intermediate, followed by second ring closure to give the desired fused benzodiazepine. The two-step protocol is further facilitated by microwave irradiation. Prudent selection of the isonitrile reagent enables the correct order of ring forming events. As such the methodology represents the first example of a post-condensation Ugi modification that employs two internal amino nucleophiles.

Mycobacterium bovis bacille Calmette–Guerin (BCG) is one of the great success stories of immunotherapy as a treatment for superficial urothelial carcinoma of the bladder. Despite clinical effectiveness in over 50% of patients, the high incidence of local side effects and presence of nonresponders has led to efforts to improve the therapy. Recent advances have suggested a role for neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in the antitumor inflammatory response. Cell wall components of mycobacteria alone, lowered doses of BCG, and combination with cytokines have been studied as ways to improve the immune response associated with BCG and/or reduce toxicity. This review will discuss the clinical use of BCG, its proposed mechanism of action, and directions of future research to improve efficacy and decrease side effects.

Numerous studies have investigated the potential use of TNF-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic since its discovery in 1995 – because TRAIL is a potent inducer of apoptosis in tumor cells but not in normal cells and tissues. Consequently, a great deal is known about TRAIL/TRAIL receptor expression, the molecular components of TRAIL receptor signaling, and methods of altering tumor cell sensitivity to TRAIL-induced apoptosis. Our laboratory was the first to report the possibility of TRAIL gene transfer therapy as an alternative method of using TRAIL as an antitumor therapy. As with recombinant proteins administered systemically, intratumoral TRAIL gene delivery also has limitations that can restrict its full potential. Translating the preclinical TRAIL studies into the clinic has started, with the hope that TRAIL will exhibit robust tumoricidal activity against human primary tumors in situ with minimal toxic side effects.

The preparation of tungstate-containing glass–ceramic composites (GCC) for the potential immobilization of radio cesium has been considered. The GCC materials were prepared by blending two oxide precursor compositions in various proportions. These included a preformed Cs-containing hexagonal tungsten bronze (HTB) phase (Cs 0.3 Ti 0.2 W 0.8 O 3 , P 6 3 / mcm ) and a blend of silica and other oxides. The use of the HTB phase was motivated on the assumption that a HTB-based adsorbent could be used to remove cesium directly from aqueous high level liquid waste feeds. In the absence of the HTB, glass–ceramics were relatively easily prepared from the Cs-containing glass-forming oxide blend. On melting the mixture a relative complex GCC phase assemblage formed. The principal components of this phase assemblage were determined using X-ray powder diffraction, 133 Cs MAS-NMR, and cross-sectional SEM and included glass, various zeolites, scheelite (CaWO 4 ) and a range of other oxide phases and Cs-containing aluminosilicate. Importantly, under no circumstance was cesium partitioned into the glass phase irrespective of whether or not the composition included the preformed Cs-containing HTB compound. For compositions containing the HTB, cesium was partitioned into one of four major phases including zeolite; Cs–silica–tungstate bronze, pollucite (CsAlSi 2 O 6 ), and an aluminosilicate with an Al/Si ratio close to one. The leach resistance of all materials was evaluated and related to the cesium distribution within the GCC phase assemblages. In general, the GCCs prepared from the HTB had superior durability compared with materials not containing tungsten. Indeed the compositions in many cases had leach resistances comparable to the best ceramics or glass materials.

Lyme disease, caused by the tick-transmitted bacterium Borrelia burgdorferi, is the most common vector-borne disease in the United States. We surveyed residents of three Connecticut health districts to evaluate the impact of intensive community-wide education programs on knowledge, attitudes, and behaviors to prevent Lyme disease. Overall, 84% of respondents reported that they knew a lot or some about Lyme disease, and 56% felt that they were very or somewhat likely to get Lyme disease in the coming year. During 2002-2004, the percentage of respondents who reported always performing tick checks increased by 7% and the percentage of respondents who reported always using repellents increased by 5%, whereas the percentage of respondents who reported avoiding wooded areas and tucking pants into socks decreased. Overall, 99% of respondents used personal protective behaviors to prevent Lyme disease. In comparison, 65% of respondents reported using environmental tick controls, and increased use of environmental tick controls was observed in only one health district. The majority of respondents were unwilling to spend more than $100 on tick control. These results provide guidance for the development of effective Lyme disease prevention programs by identifying measures most likely to be adopted by residents of Lyme disease endemic communities.

A series of zirconium titanium oxide mesophases containing 33 atom % Zr have been prepared using carboxylic acids of different alkyl chain lengths (Cy ) from y=4-18 through organic-inorganic polymer phase segregation as the gel transition is approached. Thermal treatment of these transparent gels up to 450 degrees C eliminated the organic template, and domain coarsening occurred affording stable worm-hole mesoporous materials of homogeneous composition and pore diameters varying from about 3 to 4 nm in fine increments. With such materials, it was subsequently possible to precisely study the adsorption of vanadium oxo-anions and cations from aqueous solutions and, more particularly, probe the kinetics of intraparticle mass transport as a function of the associated pore dimension. The kinetics of mass transport through the pore systems was investigated using aqueous vanadyl (VO2+) and orthovanadate (VO3(OH)2-) probe species at concentrations ranging from 10 to 200 ppm (0.2 to 4 mmol/L) and pH values of 0 and 10.5, respectively. In the case of both of these vanadium species, the zirconium titanate mesophases displayed relatively slow kinetics, taking in excess of about 500 min to achieve maximum uptake. By using a pseudo-second-order rate law, it was possible to extract the instantaneous and overall rate of the adsorption processes and then relate these to the pore diameters. Both the instantaneous and overall rates of adsorption increased with increasing surface area and pore diameter over the studied pore size range. However, the equilibrium adsorption capacity increased linearly with pore diameter only for the higher concentrations and was independent of pore diameter for the lower concentration. These results have been interpreted using a model in which discrete adsorption occurs at low concentrations and is then followed by multilayer adsorption at higher concentration.

The immunologic response to influenza virus infection, like many other viruses, is characterized by robust production of proinflammatory cytokines, including type I and II interferon (IFN), which induce a number of antiviral effects and are essential for priming the innate and adaptive cellular components of the immune response. Here, we demonstrate that influenza virus infection induces the expression of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on human peripheral blood mononuclear cell (PBMC) populations. Consistent with previous studies examining TRAIL upregulation, increased TRAIL expression correlated with increased type I and II IFN levels in PBMC cultures. Interestingly, dilution of these cytokines resulted in decreased expression of TRAIL. TRAIL upregulation was not dependent on active viral infection, and TRAIL was observed on NS-1-negative cells. Furthermore, influenza virus infection of lung adenocarcinoma cells (A549) resulted in increased sensitization to TRAIL-induced apoptosis compared with uninfected A549. Infected PBMC expressing TRAIL preferentially killed infected A549, but did not affect uninfected cells, and the addition of soluble TRAIL-R2:Fc blocked the lysis of infected cells, demonstrating TRAIL-dependent killing of infected cells. Collectively, these data demonstrate that TRAIL expression is induced on primary human innate and adaptive immune cells in response to cytokines produced during influenza infection and that TRAIL sensitivity is increased in influenza virus-infected cells. These data also suggest that TRAIL is a primary mechanism used by influenza-stimulated human PBMC to kill influenza-infected target cells and reinforce the importance of cytokines produced in response to TLR agonists in enhancing cellular immune effector functions.

Elimination of influenza virus-infected cells during primary influenza virus infections is thought to be mediated by CD8+ T cells though perforin- and FasL-mediated mechanisms. However, recent studies suggest that CD8+ T cells can also utilize TRAIL to kill virally infected cells. Therefore, we herein examined the importance of TRAIL to influenza-specific CD8+ T cell immunity and to the control of influenza virus infections. Our results show that TRAIL deficiency increases influenza-associated morbidity and influenza virus titers, and that these changes in disease severity are coupled to decreased influenza-specific CD8+ T cell cytotoxicity in TRAIL−/− mice, a decrease that occurs despite equivalent numbers of pulmonary influenza-specific CD8+ T cells. Furthermore, TRAIL expression occurs selectively on influenza-specific CD8+ T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells. Finally, we show that adoptive transfer of TRAIL+/+ but not TRAIL−/− CD8+ effector T cells alters the mortality associated with lethal dose influenza virus infections. Collectively, our results suggest that TRAIL is an important component of immunity to influenza infections and that TRAIL deficiency decreases CD8+ T cell-mediated cytotoxicity, leading to more severe influenza infections.

The leachability in water of metakaolin based geopolymers with molar ratios of Na/Al = 1 and Si/Al = 1.5–4.0 has been investigated in order to optimise the composition for the immobilisation of nuclear waste. Formulations with Si/Al of around 2 are the most suitable using the ASTM/PCT leach test method. The variability of the leach results is discussed with reference to the microstructure, compressive strength and the degree of polymerisation of the geopolymers as observed here by solid state nuclear magnetic resonance, XRD and infrared measurements.

Chartered in 1872 as the nation's first public art organization, the Fairmount Park Art Association can be used as a case study for how urban public art collections form and evolve over time. From acquisitions, purchases and donations, to new commissions and involvement with monuments and memorials, the Art Association has helped build Philadelphia's collection of cultural treasures. Programs such as Form and Function and New•Land•Marks have changed the approach to the commission process, resulting in artworks that are integrated with the site and connected to the community. Over the years the Art Association's related public art activities have included planning projects, establishing an ongoing conservation maintenance program, advocacy, documentation, and interpretation. These efforts combined with those of other entities and individuals have established Philadelphia as a public art destination with the largest collection of outdoor sculpture in the United States—an attraction for tourists that contributes to the quality of life in the city.

Remote biopsy sampling is a valuable technique to collect data on free-ranging cetaceans. Numerous researchers have evaluated effects of biopsy darting on the target animal, but biopsy sampling may also have unintentional effects on nearby nontarget animals. We evaluated reactions of target and nontarget animals during remote biopsy sampling conducted on bottlenose dolphins (Tursiops truncatus) in August 2004 off Folly Beach, South Carolina, and Jekyll Island, Georgia, USA, and in February–March and July–August 2005 off Hilton Head, South Carolina. We examined external factors that might influence response of the target animal as well as other individuals in the group. Target animals reacted to biopsy attempts 90.9% (n = 475) of the time. Of these, 97.5% (n = 432) of reactions were to biopsy hits, and 84.4% (n = 320) of all hits had reactions recorded as low. Nontarget animals reacted 21.9% (n = 1,158) of the time; interanimal distance from target animal, season, sea state, and depth affected rea...

The ion-exchange behaviour of the lamellar phosphatoantimonate phases, A 3 Sb 3 P 2 O 14 · Z H 2 O (A = H, K; Z = 5, 6) in acidic media has been explored for several trivalent lanthanides (La 3+ , Eu 3+ and Pr 3+ ) and the actinide 241 Am 3+ . The protonated phase displayed high levels of uptake for each of these cations in mildly acidic media ( 3 ) and was also shown to be tolerant of moderate levels of potassium cations. The La 3+ ↔ 3H 3 O + exchange has been further studied using thermogravimetric, variable temperature X-ray diffraction, FT-IR and 31 P MAS NMR. Difficulties in drawing conclusions regarding the siting of La 3+ at one or both of the unique ion-exchange sites of the {Sb 3 P 2 O 14 } ∞ framework were experienced due to complications arising from the presence of intercalated water. This study has demonstrated that the exchange of La 3+ leads to a proportion of the ion-exchange sites about some of the PO 4 tetrahedra being left vacant upon exchange. The utility of the phosphatoantimonate framework for removal of radiogenic lanthanide and americium from acidic media has been demonstrated.

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SummaryA molybdenum-doped sodium tungstate phase (Mo-HTB) and a porous, granular polyacrylonitrile composite variant (PAN-Mo-HTB) have been shown to effectively remove polonium-210 and lead-210 from concentrated sulphuric acid solutions (1–8 M) and a copper electrowinning electrolyte. Both forms of the exchanger were characterised by high polonium-210 and lead-210 distribution coefficients and very good selectivity for polonium-210 and lead-210 over divalent copper and iron.

Purpose: Tumor necrosis factor–related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor–positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma. 2007 Elsevier Inc. Breast cancer, TRAIL, DR4, Apoptosis.

Spatial memory impairments observed in Alzheimer's disease and schizophrenia have been attributed to many factors, including glutamate hypofunction and reduced hippocampal volume. Clonidine, a non-specific alpha(2) adrenergic receptor agonist, improves spatial memory in animals treated with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine; however, its effects on memory deficits produced by other NMDA antagonists or hippocampal damage have not been fully characterized. The purpose of this study was to determine if clonidine could alleviate memory deficits produced by the NMDA antagonist, MK-801, or by excitotoxic hippocampal damage. In the first phase of the study, male rats were pretreated with clonidine (0.01 or 0.05 mg/kg) or saline, and treated with MK-801 (0.1 mg/kg) or saline prior to discrete-trial delayed alternation or radial-arm maze testing. MK-801 impaired delayed alternation performance and increased the number of arm revisits in the radial-arm maze. Clonidine pretreatment significantly alleviated these drug-induced deficits. In the second phase of the study, excitotoxic damage was produced in the dorsal hippocampus with NMDA. Hippocampal damage produced a significant impairment in the delayed alternation task, yet pretreatment with clonidine did not alleviate this damage-induced deficit. Taken together, the data indicate that clonidine alleviates memory impairments produced by glutamate hypofunction, but not by hippocampal damage. This caveat may be important in designing treatments for memory disorders not linked to a single pathophysiological mechanism.

High levels of decoy receptor 2 (DcR2; TRAIL-R4) expression are correlated with TRAIL resistance in prostate cancer cells. In addition, upregulation of TRAIL death receptor (DR4 and DR5) expression, either by ionizing radiation or chemotherapy, can sensitize cancer cells to TRAIL. Considering more than half of human cancers are TRAIL resistant, modulation of surface TRAIL receptor expression appears to be an attractive treatment modality to counteract TRAIL resistance. In this study, three siRNA duplexes targeting DcR2 receptor were tested. Ad5hTRAIL infections were performed to overexpress human full-length TRAIL to induce cell death, and the in vitro tumorigenic potential of prostate cancer cells was assessed using colony-forming assays on soft agar. The DU145 and LNCaP prostate cancer cell lines, which express high levels of DcR2, were resistant to Ad5hTRAIL-induced death. Downregulation of surface DcR2 expression by siRNA sensitized these prostate cancer cell lines to Ad5hTRAIL. In addition, DcR2 siRNA-mediated knockdown of DcR2, followed by Ad5hTRAIL infection, dramatically reduced the in vitro tumorigenic potential of prostate cancer cells. Collectively, our results suggest the potential for combining receptor-specific siRNA with TRAIL in the treatment of certain cancers.

The simple abstraction of chloride ion from [RuCl(CO)2(η-C5H5)] using [TlBF4] proved problematic, unexpectedly giving a new complex containing linear Ru–Tl–Ru. The complex, [{Ru(CO)2(η-C5H5)}2(μ-Tl)(F–BF2–F)]∞, was polymeric, as determined by a single-crystal X-ray diffraction experiment, in which the thallium centres are bridged by the anions. In an effort to compare the nature of the Tl–Ru bonds, an additional complex was prepared by the reaction of Tl3+ ions with [Ru(CO)2(η-C5H5)]–. The resulting neutral complex, [{Ru(CO)2(η-C5H5)}3(μ-Tl)], was also structurally characterised. Quantum chemical calculations of [{Ru(CO)2(η-C5H5)}2(μ-Tl)][BF4] suggest that the Tl–Ru bond has ionic character with integrated atomic charges showing that the metal–metal bonding is best represented as Ru0–TlI–Ru0. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Titania thin films were prepared through the anodisation of titanium metal in a 1.0 M sulphuric acid solution at 80 °C utilising a series of pulsed dc constant currents of increasing magnitude. Films were then tested as a potential anode material for lithium batteries using a variety of techniques. Electrochemical testing revealed that the films (3.8 cm 2 ) offered good rate capabilities affording a constant capacity of 48 μAh for a constant current of 10 μA which decreased to 25 μAh on increasing the current to 1250 μA. Cyclic voltammetry was conducted over a range of scan rates from which capacitive currents were examined and rate constants, transfer coefficients and diffusion coefficients calculated. Electrochemical impedance spectroscopy was conducted over six potentials in the range 0.1–2.7 V with the experimental data successfully modelled using an equivalent circuit with the notation R(Q(RW))C. TEM observation of focussed ion beam milled cross-sections showed significant structural differences between the as-anodised film and those cycled in a lithium battery. Raman spectroscopy showed that the films had an anatase character that transformed into an unidentified lithium-containing, titanate phase on cycling. Based on a film thickness of 100 nm, and assuming density of 4 g cm −3 such films offered a stable capacity of 316 mAh g −1 .

Bladder cancer is a huge economic burden on the healthcare system and is responsible for approximately 5% of all cancer deaths in humans. Mycobacterium bovis BCG-based therapy is the treatment of choice for superficial bladder cancer. Bacillus Calmette-Guerin (BCG) instillation in the bladder results in a massive local inflammatory response that has secondary antitumor properties. Recent studies have demonstrated that neutrophils present in the bladder after BCG instillation release large amounts of the apoptosis-inducing molecule TRAIL, as well as chemokines that recruit other immune cells, suggesting that neutrophils play a key role in the antitumor response to BCG therapy. This review discusses the impact of these findings on the understanding of the antitumor mechanisms underlying BCG-based immunotherapy for bladder cancer.