The Star Formation Across Cosmic Time (SFACT) Survey. I. Survey Description and Early Results from a New Narrow-Band Emission-Line Galaxy Survey

We introduce the Star Formation Across Cosmic Time (SFACT) survey. SFACT is a new narrow-band survey for emission-line galaxies (ELGs) and QSOs being carried out using the wide-field imager on the WIYN 3.5 m telescope. Because of the superior depth and excellent image quality afforded by WIYN, we routinely detect ELGs to r = 25.0. Our survey observations are made using three custom narrow-band filters centered on 6590 A, 6950 A, and 7460 A. Due to the sensitivity of the survey, we are able to simultaneously detect sources via a number of different emission lines over a wide range of redshifts. The principal lines detected in SFACT are H-alpha (redshifts up to 0.144), [O III]5007 (redshifts up to 0.500) and [O II]3727 (redshifts up to 1.015). In this paper we detail the properties of the survey as well as present initial results obtained by analyzing our three pilot-study fields. These fields have yielded a total of 533 ELG candidates in an area of 1.50 square degrees (surface density of 355 ELGs per square degree). Follow-up spectra for a subset of the ELG candidates are also presented. One of the key attributes of the SFACT survey is that the ELGs are detected in discrete redshift windows that will allow us to robustly quantify the properties of the star-forming and AGN populations as a function of redshift to z = 1 and beyond. The planned acquisition of additional narrow-band filters will allow us to expand our survey to substantially higher redshifts.Comment: 27 pages, 13 figures. Accepted for publication in the Astronomical Journa

Acoustic resolution photoacoustic Doppler flowmetry using a transducer array: optimising processing for velocity contrast

This work demonstrates the first measurements of blood flow velocity using photoacoustic flowmetry (PAF) employing a transducer array. The measurements were made in a flow phantom consisting of a tube (580 μm inner diameter) containing blood flowing steadily at physiological speeds ranging from 3 mm/s to 25 mm/s. Velocity measurements were based on the generation of two successive photoacoustic (PA) signals using two laser pulses with a wavelength of 1064 nm; the PA signals were detected using a 64-element transducer array with a -6 dB detection bandwidth of 11-17 MHz. We developed a processing pipeline to optimise a cross-correlation based velocity measurement method comprising the following processing steps: image reconstruction, filtering, displacement detection, and masking. We found no difference in flow detection accuracy when choosing different image reconstruction algorithms (time reversal, Fourier transformation, and delay-and-sum). High-pass filtering and wallfiltering were however found to be essential pre-processing steps in order to recover the correct displacement information. We masked the calculated velocity map based on the amplitude of the cross-correlation function in order to define the region of interest corresponding to highest signal amplitude. These developments enabled blood flow measurements using a transducer array, bringing PAF one step closer to clinical applicability

Processing methods for photoacoustic Doppler flowmetry with a clinical ultrasound scanner

Photoacoustic flowmetry (PAF) based on time-domain cross correlation of photoacoustic signals is a promising technique for deep tissue measurement of blood flow velocity. Signal processing has previously been developed for single element transducers. Here, the processing methods for acoustic resolution PAF using a clinical ultrasound transducer array are developed and validated using a 64-element transducer array with a -6 dB detection band of 11 to 17 MHz. Measurements were performed on a flow phantom consisting of a tube (580  μm inner diameter) perfused with human blood flowing at physiological speeds ranging from 3 to 25  mm  /  s. The processing pipeline comprised: image reconstruction, filtering, displacement detection, and masking. High-pass filtering and background subtraction were found to be key preprocessing steps to enable accurate flow velocity estimates, which were calculated using a cross-correlation based method. In addition, the regions of interest in the calculated velocity maps were defined using a masking approach based on the amplitude of the cross-correlation functions. These developments enabled blood flow measurements using a transducer array, bringing PAF one step closer to clinical applicability

Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background

The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

Controlled Orientation of Active Sites in a Nanostructured Multienzyme Complex

Multistep cascade reactions in nature maximize reaction efficiency by co-assembling related enzymes. Such organization facilitates the processing of intermediates by downstream enzymes. Previously, the studies on multienzyme nanocomplexes assembled on DNA scaffolds demonstrated that closer interenzyme distance enhances the overall reaction efficiency. However, it remains unknown how the active site orientation controlled at nanoscale can have an effect on multienzyme reaction. Here, we show that controlled alignment of active sites promotes the multienzyme reaction efficiency. By genetic incorporation of a non-natural amino acid and two compatible bioorthogonal chemistries, we conjugated mannitol dehydrogenase to formate dehydrogenase with the defined active site arrangement with the residue-level accuracy. The study revealed that the multienzyme complex with the active sites directed towards each other exhibits four-fold higher relative efficiency enhancement in the cascade reaction and produces 60% more D-mannitol than the other complex with active sites directed away from each other.ope