Benchtop NMR analysis of piperazine-based drugs hyperpolarised by SABRE

Piperazine-based drugs, such as N-benzylpiperazine (BZP), became attractive in the 2000s due to possessing effects similar to amphetamines. Herein, BZP, in addition to its pyridyl analogues, 2-, 3-, and 4-pyridylmethylpiperidine (2-PMP, 3-PMP, and 4-PMP respectively) was subjected to the hyperpolarisation technique Signal Amplification By Reversible Exchange (SABRE) in order to demonstrate the use of this technique to detect these piperazine-based drugs. Although BZP was not hyperpolarised via SABRE, 2-PMP, 3-PMP, and 4-PMP were, with the ortho- and meta-pyridyl protons of 4-PMP showing the largest enhancement of 313-fold and 267-fold, respectively, in a 1.4-T detection field, following polarisation transfer at Earth's magnetic field. In addition to the freebase, 4-PMP.3HCl was also appraised by SABRE and was found not to polarise, however, the addition of increasing equivalents of triethylamine (TEA) produced the freebase, with a maximum enhancement observed upon the addition of 3 equivalents of TEA. Further addition of TEA led to a reduction in the observed enhancement. SABRE was also employed to polarise 4-PMP.3HCl (~20% w/w) in a simulated tablet to demonstrate the forensic application of the technique (138-fold enhancement for the ortho-pyridyl protons). The amount of 4-PMP.3HCl present in the simulated tablet was quantified via NMR using D₂O as a solvent and compared well to complimentary gas chromatography–mass spectrometry data. Exchanging D₂O for CD₃OD as the solvent utilised for analysis resulted in a significantly lower amount of 4-PMP.3HCl being determined, thus highlighting safeguarding issues linked to drug abuse in relation to determining the amount of active pharmaceutical ingredient present.     

On sums of powers of inverse complete quotients

For an irrational number , let denote its -th continued fraction inverse complete quotient, obtained by deleting the first partial quotients. For any positive real number , we establish the optimal linear bound on the sum of the -th powers of the first complete quotients. That is, we find the smallest constants such that for all and all irrationals .

     

Cortical disinhibition occurs in chronic neuropathic,but not in chronic nociceptive pain

Background  

The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired-pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined.     

On the imaginary simple roots of the Borcherds algebra II9,1

In a recent paper [O. Bärwald, R.W. Gebert, M. Günaydin and H. Nicolai, preprint KCL-MTH-97-22, IASSNS-HEP-97/20, PSU-TH-178, AEI-029, hep-th/9703084, to appear in Commun. Math. Phys.] it was conjectured that the imaginary simple roots of the Borcherds algebra _II9,1 at level 1 are its only ones. We here propose an independent test of this conjecture, establishing its validity for all roots of norm − 8. However, the conjecture fails for roots of norm −10 and beyond, as we show by computing the simple multiplicities down to norm −24, which turn out to be remarkably small in comparison with the corresponding E₁₀ multiplicities. Our derivation is based on a modified denominator formula combining the denominator formulas for E₁₀ and _II9,1, and provides an efficient method for determining the imaginary simple roots. In addition, we compute the E₁₀ multiplicities of all roots up to height 231, including levels up to l = 6 and norms −42.     

A-stable Runge–Kutta methods for semilinear evolution equations

We consider semilinear evolution equations for which the linear part generates a strongly continuous semigroup and the nonlinear part is sufficiently smooth on a scale of Hilbert spaces. In this setting, we prove the existence of solutions which are temporally smooth in the norm of the lowest rung of the scale for an open set of initial data on the highest rung of the scale. Under the same assumptions, we prove that a class of implicit, A-stable Runge–Kutta semidiscretizations in time of such equations are smooth as maps from open subsets of the highest rung into the lowest rung of the scale. Under the additional assumption that the linear part of the evolution equation is normal or sectorial, we prove full order convergence of the semidiscretization in time for initial data on open sets. Our results apply, in particular, to the semilinear wave equation and to the nonlinear Schrödinger equation.     

On Transfer Operators for Continued Fractions with Restricted Digits

For any non-empty subset I of the natural numbers, let _I denotethose numbers in the unit interval whose continued fractiondigits all lie in I. Define the corresponding transfer operator for , where Re (rß) = _I is the abscissa of convergence of the series . When acting on a certain Hilbert space H_I, rß, weshow that the operator L_I, rß is conjugate to an integraloperator K_I, rß. If furthermore rß is real,then K_I, rß is selfadjoint, so that L_I, rß: H_I, rß H_I, rß has purely real spectrum.It is proved that L_I, rß also has purely real spectrumwhen acting on various Hilbert or Banach spaces of holomorphicfunctions, on the nuclear space C [0, 1], and on the Fréchetspace C [0, 1]. The analytic properties of the map rß L_I, rßare investigated. For certain alphabets I of an arithmetic nature(for example, I = primes, I = squares, I an arithmetic progression,I the set of sums of two squares it is shown that rß L_I, rß admits an analytic continuation beyond thehalf-plane Re rß > _I. 2000 Mathematics SubjectClassification 37D35, 37D20, 30B70.     

Optimal ROE loan pricing with or without adverse selection

The authors describe the structural solution of the loan rate as a function of default and response risk that maximizes expected return on equity for a lender's portfolio of risky loans. Under the assumptions of our model, the non-linear differential equation for the optimizing price is found to be separable in transformed financial, response and risk variables. With an end-point condition where default-free borrowers are willing to borrow at loan rates higher than the lender's cost of funds, general solutions are obtained for cases where default probabilities may depend explicitly on the offered loan rate and where adverse selection may or may not be present. For the general solution, we suggest a numerical algorithm that involves the sequential solutions of two separate transcendental equations each one of which depends on parameters of the risk and response scores. For the special case where the borrower's default probability is conditionally independent of loan rate, it is shown that the optimal solution is independent of Basel regulations on equity capital.