Use of perfluorohexyloctane as a long-term internal tamponade agent in complicated retinal detachment surgery

PURPOSE: To report the use of perfluorohexyloctane, a liquid semifluorinated alkane that is heavier than water, as an internal tamponade agent in surgery for complicated retinal detachments. DESIGN: A consecutive interventional case series from three study centers. METHODS: In 23 consecutive eyes (23 patients, 19 men and four women, mean ± standard deviation (SD) age of 58.5 years ± 16.1) perfluorohexyloctane was used for long-term internal tamponade. Included were eyes with complicated retinal detachment involving the lower two quadrants of the fundus. Excluded were patients with diseases in the fellow eye or severe systemic disease. A pars plana vitrectomy was performed, including membrane peeling and retinotomy where necessary. RESULTS: The mean duration for perfluorohexyloctane being left in situ was 76 days (SD 37.64) (range, 35-202 days). Four weeks following the removal of perfluorohexyloctane 19 of the 23 patients had total reattachment of the retina; three eyes had a recurrence of retinal detachment. One patient was lost to follow-up. The mean follow-up after perfluorohexyloctane removal was 97 days (range, 48 to 169 days). Cataract formation or progression was noted in nine of the 10 eyes. There were two cases with high intraocular pressures. Dispersion into small droplets was observed as early as 3 days postoperatively in three of the 23 patients. At least 12 of the 23 patients had an obvious dispersion by the time of perfluorohexyloctane removal. There was no sign of optic atrophy, retinal necrosis, or retinal vascular occlusion. CONCLUSION: Perfluorohexyloctane was tolerated as a long-term internal tamponade agent without obvious signs of damage to the retina or optic disk. Of all the complications noted, the most common was that of dispersion of the perfluorohexyloctane bubble into droplets. © 2002 by Elsevier Science Inc. All rights reserved.

The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia

Pyrrolo-1,5-benzoxazepine-15 (PBOX-15) is a novel microtubule depolymerization agent that induces cell cycle arrest and subsequent apoptosis in a number of cancer cell lines. Chronic lymphocytic leukemia (CLL) is characterized by clonal expansion of predominately nonproliferating mature B cells. Here, we present data suggesting PBOX-15 is a potential therapeutic agent for CLL. We show activity of PBOX-15 in samples taken from a cohort of CLL patients (n = 55) representing both high-risk and low-risk disease. PBOX-15 exhibited cytotoxicity in CLL cells (n = 19) in a dose-dependent manner, with mean IC(50) of 0.55 mu mol/L. PBOX-15 significantly induced apoptosis in CLL cells (n = 46) including cells with poor prognostic markers: unmutated IgV(II) genes, CD38 and zeta-associated protein 70 (ZAP-70) expression, and fludarabine-resistant cells with chromosomal deletions in 17p. In addition, PBOX-15 was more potent than fludarabine in inducing apoptosis in fludarabine-sensitive cells. Pharmacologic inhibition and small interfering RNA knockdown of caspase-8 significantly inhibited PBOX-15-induced apoptosis. Pharmacologic inhibition of c-jun NH(2)-terminal kinase inhibited PBOX-15-induced apoptosis in mutated IgV(II) and ZAP-70(-) CLL cells but not in unmutated IgV(II) and ZAP-70(+) cells. PBOX-15 exhibited selective cytotoxicity in CLL cells compared with normal hematopoietic cells. Our data suggest that PBOX-15 represents a novel class of agents that are toxic toward both high-risk and low-risk CLL cells. The need for novel treatments is acute in CLL, especially for the subgroup of patients with poor clinical outcome and drug-resistant disease. This study identifies a novel agent with significant clinical potential.

PBOX-15, a novel microtubule targeting agent, induces apoptosis, upregulates death receptors, and potentiates TRAIL-mediated apoptosis in multiple myeloma cells

Background: In recent years, much progress has been made in the treatment of multiple myeloma. However, a major limitation of existing chemotherapeutic drugs is the eventual emergence of resistance; hence, the development of novel agents with new mechanisms of action is pertinent. Here, we describe the activity and mechanism of action of pyrrolo-1,5-benzoxazepine-15 (PBOX-15), a novel microtubule-targeting agent, in multiple myeloma cells.

Methods: The anti-myeloma activity of PBOX-15 was assessed using NCI-H929, KMS11, RPMI8226, and U266 cell lines, and primary myeloma cells. Cell cycle distribution, apoptosis, cytochrome c release, and mitochondrial inner membrane depolarisation were analysed by flow cytometry; gene expression analysis was carried out using TaqMan Low Density Arrays; and expression of caspase-8 and Bcl-2 family of proteins was assessed by western blot analysis.

Results: Pyrrolo-1,5-benzoxazepine-15 induced apoptosis in ex vivo myeloma cells and in myeloma cell lines. Death receptor genes were upregulated in both NCI-H929 and U266 cell lines, which displayed the highest and lowest apoptotic responses, respectively, following treatment with PBOX-15. The largest increase was detected for the death receptor 5 (DR5) gene, and cotreatment of both cell lines with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the DR5 ligand, potentiated the apoptotic response. In NCI-H929 cells, PBOX-15-induced apoptosis was shown to be caspase-8 dependent, with independent activation of extrinsic and intrinsic apoptotic pathways. A caspase-8-dependent decrease in expression of Bim(EL) preceded downregulation of other Bcl-2 proteins (Bid, Bcl-2, Mcl-1) in PBOX-15-treated NCI-H929 cells.

Conclusion: PBOX-15 induces apoptosis and potentiates TRAIL-induced cell death in multiple myeloma cells. Thus, PBOX-15 represents a promising agent, with a distinct mechanism of action, for the treatment of this malignancy. British Journal of Cancer (2011) 104, 281-289. doi: 10.1038/sj.bjc.6606035 www.bjcancer.com Published online 21 December 2010 (C) 2011 Cancer Research UK

A wideband antenna array for DVB-T based passive bistatic radar applications

A Digital Video Broadcast Terrestrial (DVB-T) based passive radar requires the development of an antenna array that performs satisfactorily over the entire DVB-T band. The array should require no mechanical adjustments to inter-element spacing to correspond to the DVB-T carrier frequency used for any particular measurement. This paper will describe the challenges involved in designing an antenna array with a bandwidth of 450 MHz. It will discuss the design procedure and demonstrate a number of simulated array configurations. The final configuration of the array will be shown as well as simulations of the expected performance over the desired frequency span.

Design of a wideband conformal array antenna system with beamforming and null steering, for application in a DVB-T based passive radar

The use of radars in detecting low flying, small targets is being explored for several decades now. However radar with counter-stealth abilities namely the passive, multistatic, low frequency radars are in the focus recently. Passive radar that uses Digital Video Broadcast Terrestrial (DVB-T) signals as illuminator of opportunity is a major contender in this area. A DVB-T based passive radar requires the development of an antenna array that performs satisfactorily over the entire DVB-T band. At Fraunhofer FHR, there is currently a need for an array antenna to be designed for operation over the 450-900 MHz range with wideband beamforming and null steering capabilities. This would add to the ability of the passive radar in detecting covert targets and would improve the performance of the system. The array should require no mechanical adjustments to inter-element spacing to correspond to the DVB-T carrier frequency used for any particular measurement. Such an array would have an increased flexibility of operation in different environment or locations.

The design of such an array antenna and the applied techniques for wideband beamforming and null steering are presented in the thesis. The interaction between the inter-element spacing, the grating lobes and the mutual couplings had to be carefully studied and an optimal solution was to be reached at that meets all the specifications of the antenna array for wideband applications. Directional beams, nulls along interference directions, low sidelobe levels, polarization aspects and operation along a wide bandwidth of 450-900 MHz were some of the key considerations.

Laugh-aware virtual agent and its impact on user amusement

In this paper we present a complete interactive system en- abled to detect human laughs and respond appropriately, by integrating the information of the human behavior and the context. Furthermore, the impact of our autonomous laughter-aware agent on the humor experience of the user and interaction between user and agent is evaluated by sub- jective and objective means. Preliminary results show that the laughter-aware agent increases the humor experience (i.e., felt amusement of the user and the funniness rating of the film clip), and creates the notion of a shared social experience, indicating that the agent is useful to elicit posi- tive humor-related affect and emotional contagion.

Integrated Low-Loss Passive SiGe Power Splitter and Combiner Operating Across 78-86 GHz Band

This paper describes the design, implementation, and characterization of a new type of passive power splitting and combining structure for use in a differential four-way power-combining amplifier operating at E-band. In order to achieve lowest insertion loss, input and output coils inductances are resonated with shunt capacitances. Simple C-L-C and L-C networks are proposed in order to compensate inductive loading due to routing line that would otherwise introduce mismatch and increase loss. Across 78-86 GHz band, measured insertion loss is about 7 dB. Measured return losses are >10 dB from 73 GHz to 94 GHz at the input port and >9 dB from 60 GHz to 94 GHz at the output port. When integrated with driver and power amplifier cells, the simulated complete circuit exhibits 18.2 dB gain and 20.3 dBm saturated output power.

Distributed passive intermodulation generation in coplanar waveguide transmission lines

A phenomenology of distributed passive intermodulation generation in coplanar waveguide transmission line is presented. The theoretical analysis is based upon the generalised nonlinear transmission line model, which accounts for the coupling of two propagating modes. The case of weak substrate nonlinearity is considered and the model is given qualitative verification through the mapping of passive intermodulation products generated in coplanar waveguide fabricated on a commercial laminate. Implications for future research are discussed. © 2012 IEEE.

How to Manipulate an Incompatibilistically Free Agent

A prominent criticism of compatibilist theories of moral responsibility is that they do not deal adequately with cases of manipulation, and particularly with induced desires. So, for example, accounts that give the conditions for responsibility in terms of the reasons-responsiveness of the mechanism governing one's decisions, as Fischer and Ravizza (1998) do, seem to leave the door open to cases such as the following.