Temperature-sensitive protein–DNA dimerizers

Programmable DNA-binding polyamides coupled to short peptides have led to the creation of synthetic artificial transcription factors. A hairpin polyamide-YPWM tetrapeptide conjugate facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. Such small molecules function as protein-DNA dimerizers that stabilize complexes at composite DNA binding sites. Here we investigate the role of the linker that connects the polyamide to the peptide. We find that a substantial degree of variability in the linker length is tolerated at lower temperatures. At physiological temperatures, the longest linker tested confers a "switch"-like property on the protein-DNA dimerizer, in that it abolishes the ability of the YPWM moiety to recruit the natural transcription factor to DNA. These observations provide design principles for future artificial transcription factors that can be externally regulated and can function in concert with the cellular regulatory circuitry

State of air quality in and outside of hospital wards in urban centres – A case study in Lahore, Pakistan

Particulate pollution in healthcare facilities is a potential threat to healthcare workers, patients and visitors. A study was carried out to monitor particulate levels in and outside of five wards of Sheikh Zayed Hospital, a tertiary healthcare facility of Lahore. Measurements indicated that the hourly mean concentrations of PM2.5 in a medical, pulmonology (chest), surgical, pediatric and nephrology ward were 78 ± 37, 86 ± 46, 94 ± 48, 169 ± 122 and 488 ± 314 µg m-3 respectively. The outside levels of PM2.5 of the same wards were 69 ± 27, 81 ± 49, 178 ± 85, 282 ± 164 and 421 ± 240 µg m-3. Indoor levels were higher than outdoors in all the wards except surgical and pediatric ward. Such elevated levels of PM can result in aggravation of the poor health status of the patients as well as affecting the hospital staff and visitors

Ecological classification of southern intertidal zones of Qeshm Island, based on CMECS model

The “Coastal and Marine Ecological Classification Standard (CMECS)”, a new approach to ecological classification, was applied to 122 km of the southern intertidal zone of Qeshm Island located the Hormouz Strait - the Persian Gulf. Two components of this model, Surface Geology (SGC) and Biotic Cover (BCC) were used. Considering the extent and geomorphological alternations of the covered area, 12 sampling sites within 5 sub-regions were designated using by GPS. In total, 60 habitats (biotopes) with 47 codes were determined; this variety of biotopes is directly related to the diverse surface geology (substrate) of the covered area. Most of the biotopes and codes were recorded in the mid-eastern coastal zone, due to heterogeneity in substrate structure associated with numerous ecological niches in rocky shores. Crustacean species such as Eriphia smithi, Thalamita prymna, Molluscan species such as Clypeomorous bifisciatus, Cerithium caeruleum and echinoderm species such as Echinometra mathaei and Ophiactis sp. were characteristic of rocky shores, while Crustacea groups including Ocypode rotundata and Dotilla sp., and Umbonium vestiarium (Mollusca) were characteristic of sandy shores. Although the highest number of codes was recorded in Zeitun Park site (Eastern coast), it did not possess the expected specific species (such as Diadema setosum, Linckia multiflora and Ophiocoma scolopendrina), that were encountered in sites with similar surface geology. This could have been caused by tourist traffic at the Zeitun Park site

Tuning the Level of Concurrency in Software Transactional Memory: An Overview of Recent Analytical, Machine Learning and Mixed Approaches

Synchronization transparency offered by Software Transactional Memory (STM) must not come at the expense of run-time efficiency, thus demanding from the STM-designer the inclusion of mechanisms properly oriented to performance and other quality indexes. Particularly, one core issue to cope with in STM is related to exploiting parallelism while also avoiding thrashing phenomena due to excessive transaction rollbacks, caused by excessively high levels of contention on logical resources, namely concurrently accessed data portions. A means to address run-time efficiency consists in dynamically determining the best-suited level of concurrency (number of threads) to be employed for running the application (or specific application phases) on top of the STM layer. For too low levels of concurrency, parallelism can be hampered. Conversely, over-dimensioning the concurrency level may give rise to the aforementioned thrashing phenomena caused by excessive data contention—an aspect which has reflections also on the side of reduced energy-efficiency. In this chapter we overview a set of recent techniques aimed at building “application-specific” performance models that can be exploited to dynamically tune the level of concurrency to the best-suited value. Although they share some base concepts while modeling the system performance vs the degree of concurrency, these techniques rely on disparate methods, such as machine learning or analytic methods (or combinations of the two), and achieve different tradeoffs in terms of the relation between the precision of the performance model and the latency for model instantiation. Implications of the different tradeoffs in real-life scenarios are also discussed

Quantitative Analysis of Cardiomyocyte Dynamics with Optical Coherence Phase Microscopy

Spectral domain optical coherence microscopy (OCM) is an interferometric imaging technique for three-dimensional reconstruction of biological samples. Phase sensitive implementation of OCM has generally been in common path interferometer configuration to obtain high phase stability, wh ich limits the numerical aperture of the imaging optics and the transverse resolution. Here, we describe the implemen tation of optical coherence phase microscope in asymmetric Linnik interferometer configuration, which provides phase stability of 0.5 milliradians along with high spatial resolution. Three-dimensional structural images and dynamic displacement images ob tained from spontaneously active cardiomyocytes demonstrate that the phase information could potentially be used for quantitative analysis of contraction dynamics, spatially resolved to sub-cellular structures

Quantitative microarray profiling of DNA-binding molecules

A high-throughput Cognate Site Identity (CSI) microarray platform interrogating all 524 800 10-base pair variable sites is correlated to quantitative DNase I footprinting data of DNA binding pyrrole-imidazole polyamides. An eight-ring hairpin polyamide programmed to target the 5 bp sequence 5'-TACGT-3' within the hypoxia response element (HRE) yielded a CSI microarray-derived sequence motif of 5'-WWACGT-3' (W = A,T). A linear beta-linked polyamide programmed to target a (GAA)_3 repeat yielded a CSI microarray-derived sequence motif of 5'-AARAARWWG-3' (R = G,A). Quantitative DNase I footprinting of selected sequences from each microarray experiment enabled quantitative prediction of K_a values across the microarray intensity spectrum

Changes in particulate matter concentrations at different altitudinal levels with environmental dynamics

Ambient air quality is defined not only by the source strength but a variety of meteorological parameters as well. In the current study, ambient concentrations of PM along with temperature and relative humidity levels were monitored at seven different locations of Pakistan. A DustTrak DRX (Model 8533, TSI Inc.) was employed for twenty four hours real time monitoring of particulate matter at the selected sites. A considerable variation was observed in the 24 hour trend of particulate matter (PM) at different locations owing to variation in meteorological conditions due to different altitudes and seasons, and natural and anthropogenic sources in the vicinity. The highest average concentrations of PM2.5 (407μg/m3 were observed at highest elevation (Makra Peak, Shogran, 3089 m) while lowest averages (102 μg/m3) were obtained at the seaside (Hawks Bay, Karachi, 0 m).On the other hand PMTotal fraction exhibited highest levels at site B (506 μg/m3) and lowest at Site A (121 μg/m3).Correlation factors were determined for PM and meteorological parameters at each location. More research needs to be conducted to have a comprehensive knowledge about the physical parameters controlling particulate dispersal at different altitudes within the country

Minimization of a Protein−DNA Dimerizer

A protein−DNA dimerizer constructed from a DNA-binding polyamide and the peptide FYPWMKG facilitates the binding of a natural transcription factor Exd to an adjacent DNA site. The Exd binding domain can be reduced to a dipeptide WM attached to the polyamide through an ε-aminohexanoic acid linker with retention of protein−DNA dimerizer activity. Screening a library of analogues indicated that the tryptophan indole moiety is more important than methionine's side chain or the N-terminal acetamide. Remarkably, switching the stereochemistry of the tryptophan residue (l to d) stabilizes the dimerizer•Exd•DNA ternary complex at 37 °C. These observations provide design principles for artificial transcription factors that may function in concert with the cellular regulatory circuitry

Use of polyethylene glycol coatings for optical fibre humidity sensing

Humidity induced change in the refractive index and thickness of the polyethylene glycol (PEG) coatings are in situ investigated for a range from 10 to 95%, using an optical waveguide spectroscopic technique. It is experimentally demonstrated that, upon humidity change, the optical and swelling characteristics of the PEG coatings can be employed to build a plastic fibre optic humidity sensor. The sensing mechanism is based on the humidity induced change in the refractive index of the PEG film, which is directly coated onto a polished segment of a plastic optical fibre with dip-coating method. It is observed that PEG, which is a highly hydrophilic material, shows no monotonic linear response to humidity but gives different characteristics for various ranges of humidity levels both in index of refraction and in thickness. It undergoes a physical phase change from a semi-crystal line structure to a gel one at around 80% relative humidity. At this phase change point, a drastic decrease occurs in the index of refraction as well as a drastic increase in the swelling of the PEG film. In addition, PEG coatings are hydrogenated in a vacuum chamber. It is observed that the hydrogen has a preventing effect on the humidity induced phase change in PEG coatings. Finally, the possibility of using PEG coatings in construction of a real plastic fibre optic humidity sensor is discussed. (C) 2008 The Optical Society of Japan