The breakdown of quantum mechanics in the presence of time machinest

General Relativity allows for the existence of closed timelike curves. Various attempts have been made to exploit this possibility and build a time machine, that is a spacetime that has closed timelike lines inside some compact domain. We examine a simple model of a time machine, and construct the quantum-mechanical propagator for free particles in the vicinity of the causality violating domain. We discover that it is impossible for such propagators to be consistent with the law of conservation of probability. We speculate on the possible deeper consequences of our calculations.This essay received the fifth award from the Gravity Research Foundation, 1992-Ed.     

Stoichiometric complexes of polyelectrolyte and azo-functionalized surfactant

The Stoichiometric (1:1) complexes, comprising of a quaternary ammonium surfactant derived from azobenzene and the anionic polyelectrolyte poly(styrene sulfonate), were studied in solution. The studies were based on UV/Visible spectroscopy. Furthermore, aqueous solutions were prepared by the addition of excess surfactant. The kinetic data (t _1/2 and % cis) for the complexes in water with added dodecyltrimethylammonium bromide (DTAB) were collected, which suggests that the 1:1 complexes are resolubilized in water by the additional DTAB.     

Synthesis of some oxazolo and oxazinopyrano[3,2-c]quinolines and their antitumor activity

3-Amino-4-hydroxy-6-phenylpyrano[3,2-c]quinoline-2,5(6H)-dione was produced by a smooth reduction of its nitro precursor. Reaction of this 3-amino-4-hydroxypyranoquinoline derivative with different electrophiles, leading to a variety of oxazolo and oxazinopyrano[3,2-c]quinoline derivatives, was described. The structure of the new products was elucidated via elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectra. Also, screening the antitumor activity of new compounds against two human cell lines (HepG-2 and HCT-116) was carried out. Some new products showed significant antitumor activities.     

Quality by Design for Development,Optimization and Characterization of Brucine Ethosomal Gel for Skin Cancer Delivery

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (3²) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.     

Pharmacological Efficacy of Ginseng against Respiratory Tract Infections

Respiratory tract infections are underestimated, as they are mild and generally not incapacitating. In clinical medicine, however, these infections are considered a prevalent problem. By 2030, the third most comprehensive reason for death worldwide will be chronic obstructive pulmonary disease (COPD), according to the World Health Organization. The current arsenal of anti-inflammatory drugs shows little or no benefits against COPD. For thousands of years, herbal drugs have been used to cure numerous illnesses; they exhibit promising results and enhance physical performance. Ginseng is one such herbal medicine, known to alleviate pro-inflammatory chemokines and cytokines (IL-2, IL-4, IFN-γ, TNF-α, IL-5, IL-6, IL-8) formed by macrophages and epithelial cells. Furthermore, the mechanisms of action of ginsenoside are still not fully understood. Various clinical trials of ginseng have exhibited a reduction of repeated colds and the flu. In this review, ginseng’s structural features, the pathogenicity of microbial infections, and the immunomodulatory, antiviral, and anti-bacterial effects of ginseng were discussed. The focus was on the latest animal studies and human clinical trials that corroborate ginseng’s role as a therapy for treating respiratory tract infections. The article concluded with future directions and significant challenges. This review would be a valuable addition to the knowledge base for researchers in understanding the promising role of ginseng in treating respiratory tract infections. Further analysis needs to be re-focused on clinical trials to study ginseng’s efficacy and safety in treating pathogenic infections and in determining ginseng-drug interactions.     

Structural modifications induced in Bayfol polycarbonate due to heavy highly energetic ions irradiations

The effects of 28 GeV ⁵⁶Fe and 13.72 GeV ²⁸Si ion irradiation on the structural properties of two types of Bayfol, namely DPF 5023 and CR 1–4 polycarbonates, have been investigated. It is worth mentioning that this report is almost the first one dealing with the topic of material changes in such a high energy range. Samples from each type of Bayfol were classified into two groups. The first group has been exposed to Fe ion fluences at levels between 2000 and 8000 ion/cm². The second group has been exposed to Si ions with similar fluences. The total energy deposited is between 27.44 and 224 E12 eV. The modifications induced in Bayfol samples due to ion irradiation have been studied using X-ray diffraction (XRD) and Fourier Transform Infrared spectroscopy. The results indicate that the Fe ion irradiation causes crosslinking in Bayfol DPF 5023, reflected as a decrease in the ordering character. Also, the tendency of Bayfol CR 1–4 to crosslinking due to Fe ion irradiation is lower than that of Bayfol DPF 5023. On the other hand, the Si ion irradiation causes mainly chain scission at the carbonate site of both types of Bayfol associated with the formation of hydroxyl group.     

An Overview of NO Signaling Pathways in Aging

Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. Herein, we review the mechanisms of NO signaling in the cardiovascular system, central nervous system (CNS), reproduction system, as well as its effects on skin, kidneys, thyroid, muscles, and on the immune system during aging. The aging-related decline in NO levels and bioavailability is also discussed in this review. The decreased NO production by endothelial nitric oxide synthase (eNOS) was revealed in the aged cardiovascular system. In the CNS, the decline of the neuronal (n)NOS production of NO was related to the impairment of memory, sleep, and cognition. NO played an important role in the aging of oocytes and aged-induced erectile dysfunction. Aging downregulated NO signaling pathways in endothelial cells resulting in skin, kidney, thyroid, and muscle disorders. Putative therapeutic agents (natural/synthetic) affecting NO signaling mechanisms in the aging process are discussed in the present study. In summary, all of the studies reviewed demonstrate that NO plays a crucial role in the cellular aging processes.     

Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent

A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 μm diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 °C vs. 37 °C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005–0.13 ml/kg). Quantitative in vivo dose–responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (>20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (4 dB) was observed at 25 °C over 20 min of insonation at 5 MHz but at 37 °C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T_g).