Inside the isomers: the tale of chiral switches

Reproduced with permission from Australian Prescriber The document attached has been archived with permission from the publisher/copyright holder.Chiral drugs are made up of molecules with the same chemical structure, but different three-dimensional arrangements. Modern manufacturing has enabled the development of products containing a single molecular arrangement. The development of these single enantiomers from chiral drugs is known as chiral switching. Enantiomers of the same drug can have different pharmacodynamic and pharmacokinetic properties. This may translate into potential health benefits, such as an improved safety margin, if one of the enantiomers has more favourable therapeutic and pharmacokinetic characteristics. However, some chiral switching has resulted in unpredicted toxicity and the withdrawal of the enantiomer from the market or a halt in its development. Drug companies are increasingly using chiral switching as a marketing strategy, but before prescribers switch to single enantiomer drugs they should look for evidence from well-conducted clinical trials that shows the chiral switch is cost-effective and improves the outcomes for patients rather than patents.A. Somogyi, F. Bochner and D. Foste

U(N|M) quantum mechanics on Kaehler manifolds

We study the extended supersymmetric quantum mechanics, with supercharges transforming in the fundamental representation of U(N|M), as realized in certain one-dimensional nonlinear sigma models with Kaehler manifolds as target space. We discuss the symmetry algebra characterizing these models and, using operatorial methods, compute the heat kernel in the limit of short propagation time. These models are relevant for studying the quantum properties of a certain class of higher spin field equations in first quantization.Comment: 21 pages, a reference adde

Non-Markovian diffusion equations and processes: analysis and simulations

In this paper we introduce and analyze a class of diffusion type equations related to certain non-Markovian stochastic processes. We start from the forward drift equation which is made non-local in time by the introduction of a suitable chosen memory kernel K(t). The resulting non-Markovian equation can be interpreted in a natural way as the evolution equation of the marginal density function of a random time process l(t). We then consider the subordinated process Y(t)=X(l(t)) where X(t) is a Markovian diffusion. The corresponding time evolution of the marginal density function of Y(t) is governed by a non-Markovian Fokker-Planck equation which involves the memory kernel K(t). We develop several applications and derive the exact solutions. We consider different stochastic models for the given equations providing path simulations.Comment: 43 pages, 19 figures, in press on Physica A (2008

Normal families of functions and groups of pseudoconformal diffeomorphisms of quaternion and octonion variables

This paper is devoted to the specific class of pseudoconformal mappings of quaternion and octonion variables. Normal families of functions are defined and investigated. Four criteria of a family being normal are proven. Then groups of pseudoconformal diffeomorphisms of quaternion and octonion manifolds are investigated. It is proven, that they are finite dimensional Lie groups for compact manifolds. Their examples are given. Many charactersitic features are found in comparison with commutative geometry over $\bf R$ or $\bf C$.Comment: 55 pages, 53 reference

Convolution-type derivatives, hitting-times of subordinators and time-changed C0C_0-semigroups

In this paper we will take under consideration subordinators and their inverse processes (hitting-times). We will present in general the governing equations of such processes by means of convolution-type integro-differential operators similar to the fractional derivatives. Furthermore we will discuss the concept of time-changed $C_0$-semigroup in case the time-change is performed by means of the hitting-time of a subordinator. We will show that such time-change give rise to bounded linear operators not preserving the semigroup property and we will present their governing equations by using again integro-differential operators. Such operators are non-local and therefore we will investigate the presence of long-range dependence.Comment: Final version, Potential analysis, 201

The Epidemiology of Herpes Simplex Virus Type-2 Infection among Pregnant Women in Rural Mysore Taluk, India

To assess the prevalence and determinants of herpes simplex virus type 2 (HSV-2) infections among pregnant women attending mobile antenatal health clinic in rural villages in Mysore Taluk, India. Methods. Between January and September 2009, 487 women from 52 villages participated in this study. Each participant consented to provide a blood sample for HSV-2 and HIV testing and underwent an interviewer-administered questionnaire. Results. HSV-2 prevalence was 6.7% (95% confidence interval (CI) 4.4–9.0), and one woman tested positive for HIV.The median age of women was 20 years and 99% of women reported having a single lifetime sex partner.Women whose sex partner traveled away from home had 2.68 (CI: 1.13–6.34) times the odds of being HSV-2 seropositive compared to women whose sex partner did not travel. Having experienced genital lesions was also associated with HSV-2 infection ( value = 0.08). Conclusion.The 6.7% HSV-2 prevalence was similar to results obtained in studies among pregnant women in other parts of India. It appeared that most women in this study contracted HSV-2 from their spouses and few regularly used condoms. This finding highlights the need for public health policies to increase awareness and education about prevention methods among women and men living in rural India

Lieb-Thirring Bound for Schr\"odinger Operators with Bernstein Functions of the Laplacian

A Lieb-Thirring bound for Schr\"odinger operators with Bernstein functions of the Laplacian is shown by functional integration techniques. Several specific cases are discussed in detail.Comment: We revised the first versio

On the order of summability of the Fourier inversion formula

In this article we show that the order of the point value, in the sense of Łojasiewicz, of a tempered distribution and the order of summability of the pointwise Fourier inversion formula are closely related. Assuming that the order of the point values and certain order of growth at infinity are given for a tempered distribution, we estimate the order of summability of the Fourier inversion formula. For Fourier series, and in other cases, it is shown that if the distribution has a distributional point value of order k, then its Fourier series is e.v. Cesàro summable to the distributional point value of order k+1. Conversely, we also show that if the pointwise Fourier inversion formula is e.v. Cesàro summable of order k, then the distribution is the (k+1)-th derivative of a locally integrable function, and the distribution has a distributional point value of order k+2. We also establish connections between orders of summability and local behavior for other Fourier inversion problems

Buprenorphine maintenance subjects are hyperalgesic and have no antinociceptive response to a very high morphine dose

Objective. Acute pain management in opioiddependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Design. Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Setting. Ambulatory. Subjects. Twelve buprenorphine-maintained subjects: once daily sublingual dose (range 5 2–22 mg); no dose change for 1.5–12 months. Ten healthy controls. Methods. Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Results. Cold pressor responses (seconds): baseline: control 34 6 6 vs buprenorphine 17 6 2 (P 5 0.009); morphine infusion-end: control 52 6 11(P 5 0.04), buprenorphine 17 6 2 (P> 0.5); electrical stimulation responses (volts): baseline: control 65 6 6 vs buprenorphine 53 6 5 (P 5 0.13); infusion-end: control 74 6 5 (P 5 0.007), buprenorphine 53 6 5 (P> 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P 5 0.03); infusion-end: control 15 (P 5 0.09), buprenorphine 12 (P< 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 6 1, buprenorphine 136 6 10. Conclusions. Buprenorphine subjects, compared with controls, were hyperalgesic (cold pressor test), did not experience antinociception, despite high plasma morphine concentrations, and experienced respiratory depression. Clinical implications are discussed.Peter Athanasos, Walter Ling, Felix Bochner, Jason M. White, and Andrew A. Somogy