Product Of Beta Research Articles

Bayesian probabilistic sensitivity analysis of Markov models for natural history of a disease: an application for cervical cancer

Background: parameter uncertainty in the Markov model’s description of a disease course was addressed. Probabilistic sensitivity analysis (PSA) is now considered the only tool that properly permits parameter uncertainty’s examination. This consists in sampling values from the parameter’s probability distributions. Methods: Markov models fitted with microsimulation were considered and methods for carrying out a PSA on transition probabilities were studied. Two Bayesian solutions were developed: for each row of the modeled transition matrix the prior distribution was assumed as a product of Beta or a Dirichlet. The two solutions differ in the source of information: several different sources for each transition in the Beta approach and a single source for each transition from a given health state in the Dirichlet. The two methods were applied to a simple cervical cancer’s model. Results : differences between posterior estimates from the two methods were negligible. Results showed that the prior variability highly influence the posterior distribution. Conclusions: the novelty of this work is the Bayesian approach that integrates the two distributions with a product of Binomial distributions likelihood. Such methods could be also applied to cohort data and their application to more complex models could be useful and unique in the cervical cancer context, as well as in other disease modeling.

How are economic policy uncertainty shocks transmitted to capital structure? Chinese evidence

PurposeThe purpose of this paper is to investigate the mechanism of transmitting economic policy uncertainty (EPU) shocks to capital structure.Design/methodology/approachThe authors adopt a novel approach that bridges the asset pricing implications of EPU and the debt-financing decisions of Chinese firms by introducing a variable “policy-risk-induced equity return” (PRER). PRER is the product of the EPU beta and the EPU shock. Differentiating firms as per the signs of the EPU beta helps to shed light on the deep questions of whether their respective leverage targets and speeds of adjustment are different and how the targets and speeds are determined.FindingsThe empirical evidence shows that it is the equity market that channels EPU shocks to capital structure through PRER in China. Firms with positive (negative) EPU betas have PRER impact negatively (positively) the leverage target, conforming to the market-timing theory. EPU and non-policy uncertainty shocks cause the speed of adjustment to change over time. Overall, the intertemporal relation between EPU and leverage is negative. These results are robust to alternative leverage measures and after controlling for non-policy uncertainty shocks and conventional firm characteristics and have implications for academic research, policymaking, market stability, and corporate financing.Originality/valueThis study is the first to probe for, and provide insights into, the underlying reason why EPU impacts capital structure by connecting asset pricing to corporate financing for a large sample of Chinese publicly traded firms.

The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma

BackgroundMelanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS).MethodsWe examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers.ResultsIn the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated β-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases.ConclusionsAPC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma.

HBB gene mutation spectrum in an Indian cohort of 1530 cases using an in-house targeted next-generation sequencing assay

Beta thalassemia major is a common genetic disorder characterized by the reduced production or absence of beta globin, a product of the haemoglobin subunit beta (HBB) gene. Every year, approximately 10,000–12,000 children with thalassemia major are born in India. Molecular methodologies like ARMS (amplification-refractory mutation system)-PCR (polymerase chain reaction) and capillary sequencing are used to detect HBB gene mutations. It is, however, challenging to achieve comprehensive coverage of the HBB gene by these methods. Next-generation sequencing (NGS) can be used to circumvent these problems. Commercial NGS panels are prohibitively expensive and hence are not routinely implemented in most laboratories. We have developed a cost-effective, highly sensitive and specific, indigenous targeted NGS assay for detecting mutations in the HBB gene. Using this custom NGS assay, we processed 1530 samples (3017 alleles), in which we detected a spectrum of 48 pathogenic/likely pathogenic variants (mutations); IVS-I-5 (c.92+5G>C) was the most common mutation detected (allele frequency (AF) 44.55%), followed by the 619-bp deletion (AF 10.74%), c.92+1G>T (AF 6.99%), c.27_28insG (AF 6.23%), c.47G>A (AF 5.77%) and c.126_129delCTTT (AF 4.71%). Additionally, we discovered a novel mutation (c.7delC) that was submitted to the HbVar database (HbVar ID 3193) as a variant of unknown significance (VUS), probably pathogenic. The targeted NGS assay developed during this study was validated using orthogonal methods and showed excellent correlation with currently available molecular methods. Additionally, this targeted NGS assay was used to analyse the mutation spectrum of the largest beta thalassemia cohort from India.

Does the CAPM Predict Returns?

We evaluate the cross-sectional performance of the CAPM in different expected market regimes. We show that CAPM-betas positively predict portfolio and individual stock returns when market returns are expected to be high, which occurs about 50% of the time. Consequently, the product of beta and the expected market return (CAPM) predicts asset returns out-of-sample, and the predictive power of the CAPM outperforms that of alternative factor models. Strategies exploiting the joint predictive power of beta and the market return predictor have average returns increasing with beta, and Sharpe ratios up to twice those of the corresponding buy-and-hold strategies.

Products of normal, beta and gamma random variables: Stein operators and distributional theory

In this paper, we extend Stein’s method to products of independent beta, gamma, generalised gamma and mean zero normal random variables. In particular, we obtain Stein operators for mixed products of these distributions, which include the classical beta, gamma and normal Stein operators as special cases. These operators lead us to closed-form expressions involving the Meijer $G$-function for the probability density function and characteristic function of the mixed product of independent beta, gamma and central normal random variables.

Wilks’ factorization of the matrix-variate Dirichlet–Riesz distributions

ABSTRACTThe Riesz distributions on positive definite symmetric matrices are used to introduce a class of Dirichlet–Riesz distributions. In addition, several distributional properties are stated. Essentially, we show the relationship between the Dirichlet–Riesz distributions of the first kind and the second kind, respectively. We derive Wilks’ factorization of the matrix-variate Dirichlet–Riesz. Further, several results on the product of Riesz and beta–Riesz matrices with a set of Dirichlet–Riesz matrices of the first kind have been derived.

Regularized Covariance Matrix Estimation in Complex Elliptically Symmetric Distributions Using the Expected Likelihood Approach—Part 2: The Under-Sampled Case

In the first part of these two papers, we extended the expected likelihood approach originally developed in the Gaussian case, to the broader class of complex elliptically symmetric (CES) distributions and complex angular central Gaussian (ACG) distributions. More precisely, we demonstrated that the probability density function (p.d.f.) of the likelihood ratio (LR) for the (unknown) actual scatter matrix Σ0 does not depend on the latter: it only depends on the density generator for the CES distribution and is distribution-free in the case of ACG distributed data, i.e., it only depends on the matrix dimension M and the number of independent training samples T, assuming that T ≥ M. Additionally, regularized scatter matrix estimates based on the EL methodology were derived. In this second part, we consider the under-sampled scenario (T ≤ M) which deserves specific treatment since conventional maximum likelihood estimates do not exist. Indeed, inference about the scatter matrix can only be made in the T-dimensional subspace spanned by the columns of the data matrix. We extend the results derived under the Gaussian assumption to the CES and ACG class of distributions. Invariance properties of the under-sampled likelihood ratio evaluated at Σ0 are presented. Remarkably enough, in the ACG case, the p.d.f. of this LR can be written in a rather simple form as a product of beta distributed random variables. The regularized schemes derived in the first part, based on the EL principle, are extended to the under-sampled scenario and assessed through numerical simulations.

Association of a satellite DNA β molecule with mesta yellow vein mosaic disease

The yellow vein mosaic disease infected mesta samples exhibited positive amplification with different primers specific for coat protein (CP) gene of DNA-A molecule of begomoviruses and full-length DNA beta molecule. The amplified product of a full-length DNA beta and the CP gene of two different isolates were cloned and sequenced. The DNA beta molecule was 1,354 nt in length having highest sequence identity (86.1%) with two reported DNA beta molecules of Indian isolates of begomovirus infecting cotton (accession number DQ191161 and AJ316038). Highest sequence identity (85.5%) of betaC1 gene product was found with that encoded by DNA beta associated with begomovirus infecting tomato (AJ316035), originating from Pakistan. The predicted betaC1 protein consisted of 118 amino acids. The nucleotide sequences of the CP genes from both was 771 nt in length and showed sequence identity with CP genes of begomoviruses infecting tomato (82.2-92.4%), tobacco (AY007616, 94.2%) and Croton (AJ507777, 93.9%). The highest percentage sequence identity (97.6%) of the CP gene product was found with that encoded by DNA-A of two isolates of begomovirus infecting tomato (AJ810364 and AJ810357). The predicted CP consisted of 256 amino acids. The results indicate for the first time that the begomovirus associated with mesta yellow vein mosaic disease contains DNA beta molecule along with DNA-A in its genome. The phylogenetic tree also indicated that the DNA beta molecule reported here is distinct from other known geminiviruses or nanovirus components.

Validated multi-component CZE-UV procedure for the quantification of human hemorphin LVV-H7 in plasma stability studies

The human hemorphin LVV-H7 is an endogenous cleavage product of the hemoglobin beta, gamma, epsilon or delta chain exhibiting potential pharmaceutical relevance for blood pressure regulation, the treatment of Alzheimer's disease or learning deficiencies. Here we present the development of a multi-component capillary zone electrophoretic method (CZE-UV), allowing the simultaneous quantification of LVV-H7 and four N-terminal degradation products generated in EDTA plasma. Hemorphins in the supernatant of precipitated plasma samples are quantified by external calibration. Validation of the procedure oriented towards international pharmaceutical guidelines and demonstrated excellent linearity (r2 > or = 0.999), good precision (repeatability and reproducibility below 11%), accuracy (-8.4%-4%), ruggedness and an appropriate lower limit of quantification (LLOQ 1.0 microg mL(-1)). This procedure was applied to stability studies of LVV-H7 in human EDTA plasma attended by profiling metabolites using qualitative MALDI-TOF MS analysis. We detected the activity of a soluble plasma form of aminopeptidase M causing successive N-terminal truncation. This is the first time that LVV-H7 degradation as well as its metabolite production have systematically been monitored by a quantitative CZE-UV procedure, underlining the growing importance of such techniques in peptide analysis. In addition, our results give useful hints for future drug development of LVV-H7.

Direct quantification of lycopene in products derived from thermally processed tomatoes: optothermal window as a selective, sensitive, and accurate analytical method without the need for preparatory steps.

The concept of the optothermal window (OW) is proposed as a reliable analytical tool to rapidly determine the concentration of lycopene in a large variety of commercial tomato products in an extremely simple way (the determination is achieved without the need for pretreatment of the sample). The OW is a relative technique as the information is deduced from the calibration curve that relates the OW data (i.e., the product of the absorption coefficient beta and the thermal diffusion length micro) with the lycopene concentration obtained from spectrophotometric measurements. The accuracy of the method has been ascertained with a high correlation coefficient (R = 0.98) between the OW data and results acquired from the same samples by means of the conventional extraction spectrophotometric method. The intrinsic precision of the OW method is quite high (better than 1%), whereas the repeatability of the determination (RSD = 0.4-9.5%, n= 3-10) is comparable to that of spectrophotometry.

Marginal distributions of sequential and generalized order statistics

Expressions for marginal distribution functions of sequential order statistics and generalized order statistics are presented without any restrictions imposed on the model parameters. The results are related to the relevation transform, to the distribution of the product of Beta distributed random variables, and to Meijer’s G-functions. Some selected applications in the areas of moments, conditional distributions, recurrence relations, and reliability properties are shown.

Comparative Enzyme Kinetics of Two Allelic Forms of Barley (Hordeum vulgare L.) Beta -amylase

The barley (Hordeum vulgare L.) varieties, Franklin and Schooner, contain two different allelic forms of beta -amylase (EC 3.2.1.2) encoded on chromosome 4H by the Bmy 1-Sd1 and Bmy 1-Sd2L alleles, respectively. The corresponding enzymes, referred to as Sd1 and Sd2L, were purified from both mature barley grain and germinated barley (green malt), and their physical and kinetic properties studied. Approximately 4 kDa were cleaved from both Sd1 and Sd2Lbeta -amylases after germination. The Kmvalue for green malt beta -amylase was less than that of mature grain beta -amylase for both varieties when potato starch was used as a substrate, although Vmaxwas similar. This indicated that proteolysis after germination increased the affinity of beta -amylase for potato starch. No significant kinetic differences were observed between beta -amylase from mature grain and green malt of the two barley varieties when amylose (degree of polymerisation 100 and 18) and maltopentaose were used as substrates. Kinetic differences were also observed between the two allelic forms of beta -amylase. Sd1 beta -amylase from green malt exhibited a lower Kmvalue for potato starch than Sd2L beta -amylase, demonstrating that at non-saturating starch concentrations Sd1 beta -amylase is better able to hydrolyse starch than Sd2L beta -amylase. As the degree of polymerisation of the substrates decreased from approximately 740 (potato starch) to 5 (maltopentaose), the Kmvalues for beta -amylase increased, whereas Vmaxvalues decreased. Maltose, the hydrolytic product of beta -amylase, was found to be a weak competitive inhibitor of both Sd1 and Sd2L green malt beta -amylases with respect to potato starch and amylose. Taken together the kinetic observations for bet a-amylase suggest that the allelic differences and C-terminal proteolysis might be exploited to improve the efficiency of starch hydrolysis during the mashing stage of the brewing process.

Cleavage of Alzheimer's Amyloid Precursor Protein (APP) by Secretases Occurs after O-Glycosylation of APP in the Protein Secretory Pathway: IDENTIFICATION OF INTRACELLULAR COMPARTMENTS IN WHICH APP CLEAVAGE OCCURS WITHOUT USING TOXIC AGENTS THAT INTERFERE WITH PROTEIN METABOLISM

beta-Amyloid peptide (Abeta) is a principal component of parenchymal amyloid deposits in Alzheimer's disease. Abeta is derived from amyloid precursor protein (APP) by proteolytic cleavage. APP is subject to N- and O-glycosylation and potential tyrosine sulfation, following protein synthesis, and is then thought to be cleaved in an intracellular secretory pathway after or during these post-translational modifications. Studies utilizing agents that affect a series of steps in the protein secretory pathway have identified the possible intracellular sites of APP cleavage and Abeta generation within the protein secretory pathway. In the present study, using cells with normal protein metabolism, but expressing mutant APP with defective O-glycosylation, we demonstrated that the majority of APP cleavage by alpha-, beta-, and gamma-secretases occurs after O-glycosylation. Cells expressing the mutant APP noticeably decreased the generation of the intracellular APP carboxyl-terminal fragment (alphaAPPCOOH), a product of alpha-secretase, and both Abeta40 and Abeta42 in medium, a product of beta- and gamma-secretases. Furthermore, we found that the cells accumulate the mutant APP in intracellular reticular compartments such as the endoplasmic reticulum. Agents that could ambiguously affect the function of specific intracellular organelles and that may be toxic were not used. The present results indicate that APP is cleaved by alpha-, beta-, and gamma-secretases in step(s) during the transport of APP through Golgi complex, where O-glycosylation occurs, or in compartments subsequent to trans-Golgi of the APP secretory pathway.

On the stochastic equation L(X)=L[B(X+C)] and a property of gamma distributions

This paper is concerned with the stochastic equation X = B(X+C), where B, X and C are independent. This equation has appeared in a number of contexts, notably in actuarial science. An apparently new property of gamma variables (Theorem 1) leads to the derivation of a new explicit example of solution of the stochastic equation (Theorem 2), where B is the product of two independent beta variables, C is gamma and X is the product of independent beta and gamma variables. Also, a number of previously known explicit examples are seen to be direct algebraic consequences of a well-known property of gamma variables.

3'- and 5'-strand cleavage reactions catalyzed by the Fpg protein from Escherichia coli occur via successive beta- and delta-elimination mechanisms, respectively.

The Fpg protein from Escherichia coli is a multifunctional protein that excises damaged purine bases from DNA to generate aldehydic abasic sites and then catalyzes the successive cleavage of the phosphodiester bonds first on the 3'-side and then on the 5'-side of the abasic site to generate 5'- and 3'-phosphate ends, respectively, thereby excising the deoxyribose residue. The mechanisms of the 3'- and 5'-strand cleavage reactions have been studied by nuclear magnetic resonance spectroscopy (NMR) and gas chromatography-mass spectrometry (GC-MS). The 3'-strand cleavage reaction is a beta-elimination reaction in which the 2'-hydrogen is abstracted and the 3'-phosphate is eliminated. The 5'-strand cleavage reaction is a delta-elimination reaction in which the 4'-hydrogen is abstracted and the 5'-phosphate is eliminated. Two types of experiments were performed to establish the occurrence of the sequential elimination reactions. First, when the reaction was performed in H2(18)O, 31P NMR demonstrated that neither phosphate group contained 18O. Second, the five-carbon product derived from the deoxyribose residue was stabilized by reduction with NaBH4 and characterized by GC-MS. The mass spectrum of the reduced product was identical to that of authentic 4-oxo-2-pentenal, the tautomerized product of successive beta- and delta-elimination reactions.

The kinetics of effect of neuromuscular blocking drugs.

In attempts to derive pharmacokinetic constants from effect data three methods were explored, using non-depolarizing neuromuscular blocking drugs as the paradigm for obtaining effect data. The first method, based on the simple assumption that following two doses, the drug concentrations at times of equal effect during recovery, were equal. Provided that recovery took place in the log-linear drug elimination phase, the elimination rate constant (beta) could be calculated. This method proved rather inaccurate, a second method, again dependent on recovery in the log-linear phase yielded a constant which was the product of beta and the exponent of the Hill equation (s). This method yielded results within 20% of values calculated from plasma drug assays, and it was demonstrated that the time-effect curve could be described from knowledge of this constant. The third method, using non-linear curve fitting technique, derived values for the rate constants of plasma redistribution (alpha) and elimination (beta) as well as for the rate constant of elimination from an effect compartment (keo). If the values were derived from the effect of two doses of a drug, the intensity and duration of effect of a third dose could be predicted with reasonable accuracy. The dose dependent constants of the usual compartmental equations for the plasma concentration of a drug (A and B) could be derived in terms of the EC50. The method can be applied to any drug whose effect can be measured and whose maximal effect can be defined. We believe that the method may be useful in rapidly and inexpensively estimating population kinetic parameters, and in screening drugs.

Ballooning-Mirror Instability and Internally Driven Pc 4-5 Wave Events.

A kinetic-MHD field-aligned eigenmode stability analysis of low frequency ballooning-mirror instabilities has been performed for anisotropic pressure plasmas in the magnetosphere. The ballooning mode is mainly a transverse wave driven unstable by pressure gradient in the bad curvature region. The mirror mode with a dominant compressional magnetic field perturbation is excited when the product of plasma beta and pressure anisotropy (P⊥/P|| > 1) is large. In the limit that the wave frequency is smaller than the energetic trapped particle magnetic drift frequency, which is usually much smaller than the energetic trapped particle bounce frequency, the energetic trapped particles experience the bounce-averaged wave structure due to their rapid bounce motion. For modes with north-south symmetric field-aligned structure of parallel perturbed magnetic field the energetic trapped particle kinetic pressure response is finite and cancels with their fluid pressure response so that the symmetric mode is stable. Physically the energetic trapped particles precess very rapidly across the B field, and their motion becomes very rigid with respect to low frequency symmetric MHD perturbations. For antisymmetric modes the energetic trapped particle kinetic pressure response from the northern hemisphere cancels with that from the southern hemisphere in a bounce period, and the instability β threshold of the antisymmetric mode is determined by the energetic particle fluid free energy. Pressure anisotropy with P⊥/P|| > 1 reduces the β|| threshold. The antisymmetric mode changes from a ballooning mode with dominant transverse magnetic field components at P⊥/P|| = 1 to a hybrid ballooning-mirror type mode with comparable transverse and compressional magnetic field components near the equator as P⊥/P|| increases. With large equatorial plasma beta (β|| ≥ Ο(1)) and pressure anisotropy (P⊥/P|| > 1) the field-aligned wave structure of antisymmetric ballooning-mirror mode resembles the multisatellite observations of a long lasting compressional Pc 5 wave event during November 14-15, 1979 (Takahashi et al., 1987). From the AMPTE/ CCE particle and magnetic field data observed during Pc 4-5 wave events we compute the ballooning-mirror instability parameters and perform a correlation study with the theoretical instability threshold. We find that compressional Pc 5 waves approximately satisfy the ballooning-mirror instability condition, and transverse Pc 4-5 waves are probably related to resonant ballooning instabilities with small pressure anisotropy.

Production Flexibility, Stochastic Separation, Hedging, and Futures Prices

We study a dynamic model where uncertainty about interim output adjustments causes producers to face price, cost and output uncertainty. Stochastically separable production decisions are independent of the producer's risk preferences and expectations and are based on the prevailing futures price as a certain output price. Conditions under which futures contracts achieve stochastic separation are established. Optimal hedging and maturity structure of futures contracts, equilibrium futures prices, and the effects of futures trading on output are studied. The systematic risk premium depends on the product of the futures beta and the covariance of the market return with production revenues. Article published by Oxford University Press on behalf of the Society for Financial Studies in its journal, The Review of Financial Studies.

Characterization of components of the anaerobic ribonucleotide reductase system from Escherichia coli.

Anaerobic growth of Escherichia coli induces an oxygen-sensitive ribonucleoside triphosphate reductase system, different from the aerobic ribonucleoside diphosphate reductase (EC 1.17.4.1) of aerobic E. coli and higher organisms (Fontecave, M., Eliasson, R., and Reichard, P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 2147-2151). We have now purified and characterized two proteins from the anaerobic system, provisionally named dA1 and dA3. dA3 is the actual ribonucleoside triphosphate reductase; dA1 has an auxiliary function. From gel filtration, dA1 and dA3 have apparent molecular masses of 27 and 145 kDa, respectively. In denaturing gel electrophoresis, dA3 gives two bands of closely related polypeptides with apparent molecular masses of 77 (beta 1) and 74 (beta 2) kDa. Immunological and structural evidence suggests that beta 2 is a degradation product of beta 1 and that the active enzyme is a dimer of beta 1. dA1 activity coincides on denaturing gels with a band of 29 kDa and thus appears to be a monomer. The reaction requires, in addition, an extract from E. coli heated for 30 min at 100 degrees C. Potassium is one required component, but one or several others remain unidentified and are provisionally designated fraction RT. With dA3, dA1, RT, and potassium ions, CTP reduction shows absolute requirements for S-adenosylmethionine, NADPH (with NADH as a less active substitute), dithiothreitol, and magnesium ions, and is strongly stimulated by ATP, probably acting as an allosteric effector. Micromolar concentrations of several chelators inhibit CTP reduction completely, suggesting the involvement of (a) transition metal(s).