Targeting Signaling Pathways in Epithelial Ovarian Cancer

Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies.

Purpose

We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets.

In Depth Review of Existing Data

In 2012, the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR) inhibitors, poly-ADP-ribose polymerase (PARP) inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy.

Conclusion

Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.     

Oral-based controlled release formulations using poly(acrylic acid) microgels

Aim: To investigate the release of hydrophobic and hydrophilic substances from tablets containing Pemulen and Carbopol as excipients. Method: The dissolution patterns of a hydrophobic (diazepam) and a hydrophilic active substance (midodrine-HCl) from different tablet formulations containing a nonmodified polyacrylic microgel (Carbopol 981 F) or a hydrophobically modified polyacrylic microgel (Pemulen®) have been studied. Possible differences in dissolution in phosphate buffer (pH 6.8) and in 0.1 M HCl between tablets produced using wet granulation and direct compression were also investigated. Results: Tablets produced by wet granulation had a greater effect on the release of active substance from the tablets. No major differences were observed in the release patterns of the hydrophilic substance midodrine-HCl from wet granulated tablets based on Carbopol and Pemulen. However, the release pattern of the more hydrophobic drug substance, diazepam, differed considerably between the two polymers. Wet granulation gave reproducible release patterns. The release patterns from the polymers differed considerably at pH 6.8 but were similar at low pH. Conclusions: The release of the diazepam from the hydrophobic polymer Pemulen was very slow, and the release was close to zero order.     

Stabilization of periodic orbits near a subcritical Hopf bifurcation in delay-coupled networks

We study networks of delay-coupled oscillators with the aim to extend time-delayed feedback control to networks. We show that unstable periodic orbits of a network can be stabilized by a noninvasive, delayed coupling. We state criteria for stabilizing the orbits by delay-coupling in networks and apply these to the case where the local dynamics is close to a subcritical Hopf bifurcation, which is representative of systems with torsion-free unstable periodic orbits. Using the multiple scale method and the master stability function approach, the network system is reduced to the normal form, and the characteristic equations for Floquet exponents are derived in an analytical form, which reveals the coupling parameters for successful stabilization. Finally, we illustrate the results by numerical simulations of the Lorenz system close to a subcritical Hopf bifurcation. The unstable periodic orbits in this system have no torsion, and hence cannot be stabilized by the conventional time delayed-feedback technique.     

Phase-matching properties for AgGaGeS4

The phase-matching conditions of AgGaGeS(4) have been measured for second-harmonic generation at 0.8 and 5.3 microm, and difference-frequency generation at 2.2, 3.6-5.1, and 4.8-11.8 microm. The improved Sellmeier equations that reproduce well the various phase-matching conditions are presented.     

Light scattering from particles located under a rough dielectric layer

A discussion is presented of the effect of roughness on the detectability of subsurface particles by means of the light-scattering method. We have studied the scattering of light by calibrated spheres located under a slightly rough dielectric surface both experimentally and theoretically. In our experiments, the scattering from slightly rough layers with nonresonant particles was dominated by the roughness, and the scattering diagram did not bear any discernible indications of the spheres. However, at resonance, the subsurface particles manifested themselves by an increase in the total scattered intensity and by well-pronounced maxima in the angular dependence of both the scattering diagram and the backscattered intensity. Theoretical calculations show that the angular positions of the maxima in the scattering diagram are essentially determined by the interference of fields scattered by the particles and by the surface, whereas the contribution of the multiple interparticle scattering is negligible. By contrast, the oscillations in the angular dependence of the backscattered intensity are due primarily to the scattering between neighboring spheres.     

Testing the immunity of active implantable medical devices to CW magnetic fields up to 1 MHz by an immersion method

This paper presents a magnetic-field system and the method developed for testing the immunity of the active implantable medical devices to continuous-wave magnetic fields in the frequency range up to 1 MHz. The system is able to produce magnetic fields of 150 A/m for frequencies up to 100 kHz and strengths decreasing as 1/f between 100 kHz and 1 MHz, with uniformity of the field within +/-2.5% in the volume for tests. To simulate human tissue, the medical device, together with its leads, is placed on a plastic grid in a saline tank that is introduced in the magnetic field of the induction coil. This paper offers an alternative for the injection voltage methods provided in the actual standards for assessing the protection of the implantable medical devices from the effects of the magnetic fields up to 1 MHz. This paper presents the equipment and signals used, the test procedure, and results from the preliminary tests performed at the Food and Drug Administration-Center for Devices and Radiological Health on implantable pacemakers and neurostimulators. The new system and test method are useful for the EMC research on the implantable medical devices.     

Process design of waste gas treatment from Emirates Gold Refinery

In this case study, the process modifications and improvement to the existing process at the Emirates Gold refinery (in order to meet the United Arab Emirates (UAE) nitrogen oxides air emission regulations) is presented. In the past, Emirates Gold refinery used a single small scrubber to treat waste gases. In order to treat the waste gas efficiently, it was found that a cooled oxidation reactor (oxidizer) before the existing scrubber, as well as a second scrubber is needed. The waste gas is mixed with air at a fixed ratio before entering the oxidizer which is designed to obtain the optimum degree of NO oxidation (about 50%).To keep the oxidation reactions in the desirable direction the temperature should be kept between 15 and 20°C There for an internal cooler was required. The gas mixture from the Oxidizer enters the first scrubber (existing) where most of the NO _x , mainly as N₂O₃, are absorbed by a NaOH solution (15–20%). The remaining NO _x , mainly as N₂O₃ is absorbed in the second scrubber by a NaOH solution (8–10%). The mass transfer area of the packing in the two scrubbers, the solution circulation rate, and the cooling duty were designed to reach the desired degree of absorption of N₂O₃ and NO₂. This ensures that the recommended NO _x residual value of 500 mg/m³ (250 ppm) is reached. All reactions occur simultaneously was calculated using EQ4WIN software. The data obtained for different temperatures was processed with Stat View, SuperPro Designer simulation and Aspen HYSYS simulation.     

Update: An Efficient Synthesis of Poly(ethylene glycol)‐Supported Iron(II) Porphyrin Using a Click Reaction and its Application for the Catalytic Olefination of Aldehydes

The facile synthesis of polyethylene glycol (PEG)‐immobilized iron(II) porphyrin using a copper‐catalyzed azide‐alkyne [3+2] cycloaddition “click” reaction is reported. The prepared complex 5 (PEG‐C₅₁H₃₉FeN₇O) was found to be an efficient catalyst for the selective olefination of aldehydes with ethyl diazoacetate in the presence of triphenylphosphine, and afforded excellent olefin yields with high (E) selectivities. The PEG‐supported catalyst 5 was readily recovered by precipitation and filtration, and was recycled through ten runs without significant activity loss.     

Formaldehyde exposure at various workplaces

The results of formaldehyde determinations in the air at various workplaces in the period 1980-1988 are presented. The airborne concentrations varied between less than 0.01 and 10.9 mg m-3 (mean 0.7 mg m-3). For ambient air monitoring, active sampling and capillary gas chromatography are reliable and sensitive methods. Formic acid excretion in urine is an unspecific and insensitive biological indicator for monitoring low-dose formaldehyde exposure.