Syntheses of possible steroid intermediates in bile acid biosynthesis

The structural relationship of cholesterol and bile acids was established on a chemical basis as early as the beginning of the 20th Century by Windaus. (For a review see "Steroids" by Fieser and Fieser.) but the first direct evidence that cholesterol was a biological precursor of bile acids was reported in 1943 (Bloch et.al J.Biol.Cliem. 149, 511). Since then, many studies on the degradation of cholesterol to bile acids have been made. These studies require postulated synthesized intermediates for biological testing, therefore the chemical synthesis of hypothetical intermediates is important. The main pathway for the biogenesis of cholic acid possibly involves initial hydroxylation of cholesterol at the 7α-position, followed by oxidation of the 3ß-hydroxyl group to give cholest-4-en-3-one-7α-ol. The 12α-hydroxyl group is probably then inserted and the molecule then reduced to the 5ß-cholestan-3α,7α,12α-triol. This is followed by co-oxidation of the side chain and then ß-oxidation and cleavage to cholic acid. The subject has been reviewed in this workThe aim of the present work was to produce a series of cholesterol derivatives which may be intermediates in cholesterol metabolism in living cells. In certain cases newer methods for the synthesis of known sterols were evolved. Methods for the improved separation of certain sterols had also to be worked out, and modern methods for criteria of purity were examined.The 7α-hydroxy derivatives of cholesterol, 12α-, 24, 25 and II <J6-bydroxycholesterols - the triols, were prepared through the respective 7α-hydroperoxides by means of photosensitized oxygenations. Studies with the cholesterol-4-C¹⁴ revealed that with either very dilute solutions or concentrated solutions, the attack of molecular oxygen was not as highly specific as often stated. The stereospecificity of the mode of attack of molecular oxygen has been reviewed. The isolation of cholest-4-en-3ß,6ß-diol in photosensitized oxygenation of cholesterol is reported and its mode of formation discussed.It is known that the 12α-hydroxylation reaction does not occur after either the 26-hydroxylation has been effected or the side chain oxidised to a C₂₄-acid. Certain novel compounds such as cholest-5-en-3ß,7α,24Σ-triol and cholest-5- en-3ß,7α,25-triol, are in the course of tritiation and the in vitro studies will be of interest to ascertain whether they are converted into cholic acid.The substance 7ß-hydroxycholesterol was prepared by the NaBH₄ reduction of 7-ketocholesterol. Separation of the 7α and 7ß-epimers was achieved by chromatography of the diacetate as well as the free diols on neutral alumina. For successful separation of the free diols the amount of water in the alumina was critical. No separation was possible when no water was used, while the best separation was obtained with 1% water in the support.The sterol, 12α-hydrocholesterol was prepared by a modified method of Danielsson (1963b)Deoxycholic acid was coupled with isovaleric acid, and 5ß-cholestan-3α,12α-diol thus obtained was oxidised to the 3-oxo compound by an Oppenauer method. The 4,5—double bond was introduced using SeO₂ in ethanol and cholest-4—en—3—one-12α-ol obtained in good yields. The reported method of Danielsson involved a 3-stage synthesis for the introduction of a 4,5-double bond, and the yields were low. The reduction of the enol-acetate of the oc,/3-unsaturated ketone with NaBH₄ gave the desired product. The working up procedure was also modified, and a new compound cholest-3,5-diene-12α-ol was isolated and identified as a side productAnother new compound i.e. 5ß-cholestan-3α,12α-diol-24-one was prepared by utilizing the known reaction of an acid chloride and di-isopropyl-cadmium. This compound could be used to prepare cholest-5-en-3ß,12α,24Σ-triol using the sequence of reaction described previously. Another interesting biological compound, cholest-5-en-3ß,7α,12α,24Σ-tetrol, can be obtained from this triol on photo-oxygenation and reduction as described in this work.The 4ß, 22Σ, 24, 25, 26—hydroxycholesterols were prepared by modifications of the reported methods and 26-hydrocholesterol was prepared by two different routes. An impurity separated from 25-keto-nor-cholesterol acetate was identified as 3ß-acetoxy-20-hydroxy-5-cholenic acid lactone.Cholestun-3ß,5α,6ß-triol, cholestan-3ß,5α-diol-6-one, 5α,6α-epoxycholesterol, cholest-6-en-3ß,5α-diol and cholestan- 3ß,5α-diol were prepared essentially by known methods.Cholest-4-en-3-one-7α-ol was prepared by a known sequence but modification was made in the preparation of cholest-4,6- diene-3-one by the use of chloranil in the dehydrogenation of cholest-4-en-3-one.A number of intermediates involved in the inversion of the configuration at C₃ and the saturation of the double bond were synthesized. The starting materials for these compounds were saturated coprostanes, which were prepared by electrolytic coupling of the respective bile acids and isovaleric acid.However, there are still gaps in our knowledge of complete sequence of the degradation of cholesterol to the bile acids. A comprehensive understanding of the subject will only be possible when all the relevent hypothetical intermediates have been synthesized and are available for biological experiments

Visibility based angular power spectrum estimation in low frequency radio interferometric observations

We present two estimators to quantify the angular power spectrum of the sky signal directly from the visibilities measured in radio interferometric observations. This is relevant for both the foregrounds and the cosmological 21-cm signal buried therein. The discussion here is restricted to the Galactic synchrotron radiation, the most dominant foreground component after point source removal. Our theoretical analysis is validated using simulations at 150 MHz, mainly for GMRT and also briefly for LOFAR. The Bare Estimator uses pairwise correlations of the measured visibilities, while the Tapered Gridded Estimator uses the visibilities after gridding in the uv plane. The former is very precise, but computationally expensive for large data. The latter has a lower precision, but takes less computation time which is proportional to the data volume. The latter also allows tapering of the sky response leading to sidelobe suppression, an useful ingredient for foreground removal. Both estimators avoid the positive bias that arises due to the system noise. We consider amplitude and phase errors of the gain, and the w-term as possible sources of errors . We find that the estimated angular power spectrum is exponentially sensitive to the variance of the phase errors but insensitive to amplitude errors. The statistical uncertainties of the estimators are affected by both amplitude and phase errors. The w-term does not have a significant effect at the angular scales of our interest. We propose the Tapered Gridded Estimator as an effective tool to observationally quantify both foregrounds and the cosmological 21-cm signal.Comment: 20 pages, 15 figures, 1 table.One typo corrected in Fig.13. Accepted for publication in MNRA

The prospects of measuring the angular power spectrum of the diffuse Galactic synchrotron emission with SKA1 Low

The diffuse Galactic synchrotron emission (DGSE) is the most important diffuse foreground component for future cosmological 21-cm observations. The DGSE is also an important probe of the cosmic ray electron and magnetic field distributions in the turbulent interstellar medium (ISM) of our Galaxy. In this paper we briefly review the Tapered Gridded Estimator (TGE) which can be used to quantify the angular power spectrum of the sky signal directly from the visibilities measured in radio-interferometric observations. The salient features of the TGE are (1.) it deals with the gridded data which makes it computationally very fast (2.) it avoids a positive noise bias which normally arises from the system noise inherent to the visibility data, and (3.) it allows us to taper the sky response and thereby suppresses the contribution from unsubtracted point sources in the outer parts and the sidelobes of the antenna beam pattern. We also summarize earlier work where the TGE was used to measure the C_l of the DGSE using 150 MHz GMRT data. Earlier measurements of the angular power spectrum are restricted to smaller angular multipole l ~ 10^3 for the DGSE, the signal at the larger l values is dominated by the residual point sources after source subtraction. The higher sensitivity of the upcoming SKA1 Low will allow the point sources to be subtracted to a fainter level than possible with existing telescopes. We predict that it will be possible to measure the angular power spectrum of the DGSE to larger values of l with SKA1 Low. Our results show that it should be possible to achieve l_{max} ~ 10^4 and ~ 10^5 with 2 minutes and 10 hours of observations respectively.Comment: 10 pages, 3 figures; Accepted for publication in Journal of Astrophysics and Astronomy (JOAA) special issue on "Science with the SKA: an Indian perspective

Validating a novel angular power spectrum estimator using simulated low frequency radio-interferometric data

The "Tapered Gridded Estimator" (TGE) is a novel way to directly estimate the angular power spectrum from radio-interferometric visibility data that reduces the computation by efficiently gridding the data, consistently removes the noise bias, and suppresses the foreground contamination to a large extent by tapering the primary beam response through an appropriate convolution in the visibility domain. Here we demonstrate the effectiveness of TGE in recovering the diffuse emission power spectrum through numerical simulations. We present details of the simulation used to generate low frequency visibility data for sky model with extragalactic compact radio sources and diffuse Galactic synchrotron emission. We then use different imaging strategies to identify the most effective option of point source subtraction and to study the underlying diffuse emission. Finally, we apply TGE to the residual data to measure the angular power spectrum, and assess the impact of incomplete point source subtraction in recovering the input power spectrum $C_{\ell}$ of the synchrotron emission. This estimator is found to successfully recovers the $C_{\ell}$ of input model from the residual visibility data. These results are relevant for measuring the diffuse emission like the Galactic synchrotron emission. It is also an important step towards characterizing and removing both diffuse and compact foreground emission in order to detect the redshifted $21\, {\rm cm}$ signal from the Epoch of Reionization.Comment: 18 pages, 1 table, 9 figures, Accepted for publication in New Astronom

The visibility based Tapered Gridded Estimator (TGE) for the redshifted 21-cm power spectrum

We present the improved visibility based Tapered Gridded Estimator (TGE) for the power spectrum of the diffuse sky signal. The visibilities are gridded to reduce the computation, and tapered through a convolution to suppress the contribution from the outer regions of the telescope's field of view. The TGE also internally estimates the noise bias, and subtracts this out to give an unbiased estimate of the power spectrum. An earlier version of the 2D TGE for the angular power spectrum $C_{\ell}$ is improved and then extended to obtain the 3D TGE for the power spectrum $P({\bf k})$ of the 21-cm brightness temperature fluctuations. Analytic formulas are also presented for predicting the variance of the binned power spectrum. The estimator and its variance predictions are validated using simulations of $150 \, {\rm MHz}$ GMRT observations. We find that the estimator accurately recovers the input model for the 1D Spherical Power Spectrum $P(k)$ and the 2D Cylindrical Power Spectrum $P(k_\perp,k_\parallel)$, and the predicted variance is also in reasonably good agreement with the simulations.Comment: 19 pages, 13 figures. Accepted for publication in MNRAS. The definitive version will be available at http://mnrasl.oxfordjournals.org

Measuring the History of Cosmic Reionization using the 21-cm PDF from Simulations

The 21-cm PDF (i.e., distribution of pixel brightness temperatures) is expected to be highly non-Gaussian during reionization and to provide important information on the distribution of density and ionization. We measure the 21-cm PDF as a function of redshift in a large simulation of cosmic reionization and propose a simple empirical fit. Guided by the simulated PDF, we then carry out a maximum likelihood analysis of the ability of upcoming experiments to measure the shape of the 21-cm PDF and derive from it the cosmic reionization history. Under the strongest assumptions, we find that upcoming experiments can measure the reionization history in the mid to late stages of reionization to 1-10% accuracy. Under a more flexible approach that allows for four free parameters at each redshift, a similar accuracy requires the lower noise levels of second-generation 21-cm experiments.Comment: 13 pages, 16 figures, submitted to MNRA

GMRT observation towards detecting the Post-reionization 21-cm signal

We have analyzed 610 MHz GMRT observations towards detecting the redshifted 21-cm signal from z=1.32. The multi-frequency angular power spectrum C_l(Delta nu) is used to characterize the statistical properties of the background radiation across angular scales ~20" to 10', and a frequency bandwidth of 7.5 MHz with resolution 125 kHz. The measured C_l(Delta nu) which ranges from 7 mK^2 to 18 mK^2 is dominated by foregrounds, the expected HI signal C_l^HI(Delta nu) ~10^{-6}- 10^{-7} mK^2 is several orders of magnitude smaller. The foregrounds, believed to originate from continuum sources, is expected to vary smoothly with Delta nu whereas the HI signal decorrelates within ~0.5 MHz and this holds the promise of separating the two. For each l, we use the interval 0.5 < Delta nu < 7.5 MHz to fit a fourth order polynomial which is subtracted from the measured C_l(Delta nu) to remove any smoothly varying component across the entire bandwidth Delta nu < 7.5 MHz. The residual C_l(Delta nu), we find, has an oscillatory pattern with amplitude and period respectively ~0.1 mK^2 and Delta nu = 3 MHz at the smallest l value of 1476, and the amplitude and period decreasing with increasing l. Applying a suitably chosen high pass filter, we are able to remove the residual oscillatory pattern for l=1476 where the residual C_l(Delta nu) is now consistent with zero at the 3-sigma noise level. We conclude that we have successfully removed the foregrounds at l=1476 and the residuals are consistent with noise. We use this to place an upper limit on the HI signal whose amplitude is determined by x_HI b where x_HI and b are the HI neutral fraction and the HI bias respectively. A value of x_HI b greater than 7.95 would have been detected in our observation, and is therefore ruled out at the 3-sigma level. (abridged)Comment: 29 pages, 13 figures, Accepted to MNRA

All-sky angular power spectrum – I. Estimating brightness temperature fluctuations using the 150-MHz TGSS survey

Measurements of the Galactic synchrotron emission are important for the 21-cm studies of the epoch of reionization. The study of synchrotron emission is also useful for quantifying the fluctuations in the magnetic field and the cosmic-ray electron density of the turbulent interstellar medium (ISM) of our Galaxy. Here, we present the all-sky angular power spectrum (Cℓ) measurements of the diffuse synchrotron emission obtained using the TIFR GMRT Sky Survey (TGSS) at 150 MHz