Theoretical investigation of the scope of sequential ligand tuning using a bifunctional scorpionate tris(1,2,4-triazolyl)borate-based architecture

The donor properties of a series of tripodal mixed N-donor/carbene ligands derived through sequential alkylation of hydrotris(1,2,4-triazolyl)borate have been investigated by density functional theory (DFT) methods. The structures of complexes of the form [Mo(L)(CO)3]- were optimized (L = [HB(1,2,4-triazolyl)n(1,2,4-triazol-5-ylidene)3-n]- (n = 0 – 3), hydrotris(pyrazolyl)borate, hydrotris(3,5-dimethylpyrazolyl)borate and hydrotris(imidazol-2-ylidene)borate) and nuCO frequencies for these complexes and partial charges of their Mo(CO)3 fragments were determined. Results show that ligand donation is highly tunable when compared to similar experimentally known ligands with a shift in the symmetric nuCO stretching mode of -39 cm -1 on going from the tris(1,2,4-triazolyl)borate complexes to that of the triscarbene hydrotris(1,2,4-triazol-5-ylidene) and an increase in partial charge (distributed multipole analysis) of the Mo(CO)3 fragment from -0.23 to -0.48

Evolutionary history of LINE-1 in the major clades of placental mammals

BACKGROUND: LINE-1 constitutes an important component of mammalian genomes. It has a dynamic evolutionary history characterized by the rise, fall and replacement of subfamilies. Most data concerning LINE-1 biology and evolution are derived from the human and mouse genomes and are often assumed to hold for all placentals. METHODOLOGY: To examine LINE-1 relationships, sequences from the 3′ region of the reverse transcriptase from 21 species (representing 13 orders across Afrotheria, Xenarthra, Supraprimates and Laurasiatheria) were obtained from whole genome sequence assemblies, or by PCR with degenerate primers. These sequences were aligned and analysed. PRINCIPAL FINDINGS: Our analysis reflects accepted placental relationships suggesting mostly lineage-specific LINE-1 families. The data provide clear support for several clades including Glires, Supraprimates, Laurasiatheria, Boreoeutheria, Xenarthra and Afrotheria. Within the afrotherian LINE-1 (AfroLINE) clade, our tree supports Paenungulata, Afroinsectivora and Afroinsectiphillia. Xenarthran LINE-1 (XenaLINE) falls sister to AfroLINE, providing some support for the Atlantogenata (Xenarthra+Afrotheria) hypothesis. SIGNIFICANCE: LINEs and SINEs make up approximately half of all placental genomes, so understanding their dynamics is an essential aspect of comparative genomics. Importantly, a tree of LINE-1 offers a different view of the root, as long edges (branches) such as that to marsupials are shortened and/or broken up. Additionally, a robust phylogeny of diverse LINE-1 is essential in testing that site-specific LINE-1 insertions, often regarded as homoplasy-free phylogenetic markers, are indeed unique and not convergent

Long-Term Optical Observations Of Two Lmxbs: Uw Crb (=Ms 1603+260) And V1408 Aql (=4U 1957+115)

We present new optical photometry of two low-mass X-ray binary stars, UW CrB (MS 1603+260) and V1408 Aql (4U 1957+115). UW CrB is an eclipsing binary and we refine its eclipse ephemeris and measure an upper limit to the rate of change of its orbital period, vertical bar P vertical bar < 4.2 x 10(-11) (unitless). The light curve of UW CrB shows optical counterparts of type I X-ray bursts. We tabulate the times, orbital phases, and fluences of 33 bursts and show that the optical flux in the bursts comes primarily from the accretion disk, not from the secondary star. The new observations are consistent with a model in which the accretion disk in UW CrB is asymmetric and precesses in the prograde direction with a period of similar to 5.5 days. The light curve of V1408 Aql has a low-amplitude modulation at its 9.33 hr orbital period. The modulation remained a nearly pure sine curve in the new data as it was in 1984 and 2008, but its mean amplitude was lower, 18% against 23% in the earlier data. A model in which the orbital modulation is caused by the varying aspect of the heated face of the secondary star continues to give an excellent fit to the light curve. We derive a much improved orbital ephemeris for the system.NSF 0958783Astronom

BiofilmQuant: A Computer-Assisted Tool for Dental Biofilm Quantification

Dental biofilm is the deposition of microbial material over a tooth substratum. Several methods have recently been reported in the literature for biofilm quantification; however, at best they provide a barely automated solution requiring significant input needed from the human expert. On the contrary, state-of-the-art automatic biofilm methods fail to make their way into clinical practice because of the lack of effective mechanism to incorporate human input to handle praxis or misclassified regions. Manual delineation, the current gold standard, is time consuming and subject to expert bias. In this paper, we introduce a new semi-automated software tool, BiofilmQuant, for dental biofilm quantification in quantitative light-induced fluorescence (QLF) images. The software uses a robust statistical modeling approach to automatically segment the QLF image into three classes (background, biofilm, and tooth substratum) based on the training data. This initial segmentation has shown a high degree of consistency and precision on more than 200 test QLF dental scans. Further, the proposed software provides the clinicians full control to fix any misclassified areas using a single click. In addition, BiofilmQuant also provides a complete solution for the longitudinal quantitative analysis of biofilm of the full set of teeth, providing greater ease of usability.Comment: 4 pages, 4 figures, 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2014

A Statistical Modeling Approach to Computer-Aided Quantification of Dental Biofilm

Biofilm is a formation of microbial material on tooth substrata. Several methods to quantify dental biofilm coverage have recently been reported in the literature, but at best they provide a semi-automated approach to quantification with significant input from a human grader that comes with the graders bias of what are foreground, background, biofilm, and tooth. Additionally, human assessment indices limit the resolution of the quantification scale; most commercial scales use five levels of quantification for biofilm coverage (0%, 25%, 50%, 75%, and 100%). On the other hand, current state-of-the-art techniques in automatic plaque quantification fail to make their way into practical applications owing to their inability to incorporate human input to handle misclassifications. This paper proposes a new interactive method for biofilm quantification in Quantitative light-induced fluorescence (QLF) images of canine teeth that is independent of the perceptual bias of the grader. The method partitions a QLF image into segments of uniform texture and intensity called superpixels; every superpixel is statistically modeled as a realization of a single 2D Gaussian Markov random field (GMRF) whose parameters are estimated; the superpixel is then assigned to one of three classes (background, biofilm, tooth substratum) based on the training set of data. The quantification results show a high degree of consistency and precision. At the same time, the proposed method gives pathologists full control to post-process the automatic quantification by flipping misclassified superpixels to a different state (background, tooth, biofilm) with a single click, providing greater usability than simply marking the boundaries of biofilm and tooth as done by current state-of-the-art methods.Comment: 10 pages, 7 figures, Journal of Biomedical and Health Informatics 2014. keywords: {Biomedical imaging;Calibration;Dentistry;Estimation;Image segmentation;Manuals;Teeth}, http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=6758338&isnumber=636350

Maximizing the Delivery Performance of Point-of-Care CD4+ T-Cell Counting Tests in Resource-Limited Settings - A Policy Brief

Managing HIV/AIDS presents challenges to public health policymakers, frontline workers, and researchers worldwide. A key strategy in the disease management is early diagnosis and rapid treatment initiation. While the technological field of point‐of‐care HIV/AIDS diagnostics has advanced significantly in the past two decades, several critical issues remain that hinder the deployment of point‐of‐care testing devices in resource‐deprived settings. In this policy brief, we discuss these issues, including technological specifics of point‐of‐care CD4+ T‐cell counting approaches and requirements of deploying them. We also discuss cultural and religious concerns on the deployment. At the end of the brief, we propose a roadmap for the efficient and cost‐effective deployment and call for action to assemble multidisciplinary teams for the undertaking. We argue that joint effort must be taken to conduct research and development for low‐cost portable point‐of‐care testing and for tailoring the technology deployment and care delivery support system design for specific cohorts

Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles.

Treatment of dyslipidemia patients with lipid-lowering drugs leads to a significant reduction in low-density lipoproteins (LDL) level and a low to moderate level of increase in high-density lipoprotein (HDL) cholesterol in plasma. However, a possible role of these drugs in altering morphology and distribution of cholesterol particles is poorly understood. Here, we describe the in vitro evaluation of lipid-lowering drug effects in modulating morphological features of cholesterol particles using the plaque array method in combination with imaging flow cytometry. Image analyses of the cholesterol particles indicated that lovastatin, simvastatin, ezetimibe, and atorvastatin induce the formation of both globular and linear strand-shaped particles, whereas niacin, fibrates, fluvastatin, and rosuvastatin induce the formation of only globular-shaped particles. Next, purified very low-density lipoprotein (VLDL) and LDL particles incubated with these drugs showed changes in the morphology and image texture of cholesterol particles subpopulations. Furthermore, screening of 50 serum samples revealed the presence of a higher level of linear shaped HDL cholesterol particles in subjects with dyslipidemia (mean of 18.3%) compared to the age-matched normal (mean of 11.1%) samples. We also observed considerable variations in lipid-lowering drug effects on reducing linear shaped LDL and HDL cholesterol particles formation in serum samples. These findings indicate that lipid-lowering drugs, in addition to their cell-mediated hypolipidemic effects, may directly modulate morphology of cholesterol particles by a non-enzymatic mechanism of action. The outcomes of these results have potential to inform diagnosis of atherosclerosis and predict optimal lipid-lowering therapy

Empirical Desert, Individual Prevention, and Limiting Retributivism: A Reply

A number of articles and empirical studies over the past decade, most by Paul Robinson and co-authors, have suggested a relationship between the extent of the criminal law\u27s reputation for being just in its distribution of criminal liability and punishment in the eyes of the community – its moral credibility – and its ability to gain that community\u27s deference and compliance through a variety of mechanisms that enhance its crime-control effectiveness. This has led to proposals to have criminal liability and punishment rules reflect lay intuitions of justice – empirical desert – as a means of enhancing the system\u27s moral credibility. In a recent article, Christopher Slobogin and Lauren Brinkley-Rubinstein (SBR) report seven sets of studies that they argue undermine these claims of empirical desert and moral credibility and instead support SBR\u27s proposed distributive principle of individual prevention, a view that focuses on an offender\u27s future dangerousness rather than on his perceived desert. The idea that there is a relationship between the criminal law\u27s reputation for justness and its crime-control effectiveness did not originate with Robinson and his co-authors. Rather, it has been a common theme among a wide range of punishment theory scholars for many decades. A particularly important conclusion of recent Robinson studies, however, is their confirmation that this relationship is a continuous one: even small nudges in moral credibility can produce corresponding changes in the community\u27s deference to the criminal law. This is important because it shows that even piecemeal changes or changes at the margin – as in reforming even one unjust doctrine or procedure – can have real implications for crime-control. SBR\u27s studies, rather than contradicting the crime-control power of empirical desert, in fact confirm it. Further, SBR\u27s studies do not provide support for their proposed individual prevention distributive principle, contrary to what they claim. While SBR try to associate their principle with the popular limiting retributivism adopted by the American Law Institute in its 2007 amendment of the Model Penal Code, in fact it is, in many respects, just the reverse of that principle. With limiting retributivism, the Model Code\u27s new provision sets desert as dominant, never allowing punishment to conflict with it. SBR would have punishment essentially always set according to future dangerousness; it is to be constrained by desert only when the extent of the resulting injustices or failures of justice is so egregious as to significantly delegitimize the government and its law. This ignores the fact that even minor departures from justice may have an important cumulative effect on the system as a whole. What SBR propose – essentially substituting preventive detention for criminal justice – promotes the worst of the failed policies of the 1960s, where detention decisions were made at the back-end by experts, and conflicts with the trend of the past several decades of encouraging more community involvement in criminal punishment, not less

High-Throughput Nanoliter Dispensing Device for Biological Applications

Pathogen identification is a field that can contribute largely to the prevention of the spreading of illness and disease. In the past, pathogen identification has been a long and arduous process due to the time-consuming processes and steps that requires technician’s time and effort. With new technologies emerging however, screening of bacteria colonies can be done in a quick and high-throughput way. The problem is that using the current methods, bacteria cannot be transferred to petri dishes fast enough to keep up with the new screening methods. The current study focuses on exploring different methods to create an ergonomic device that can dispense and inoculate bacteria cells onto petri dishes in a fast, repeatable, and high-throughput manner. The testing of bacteria in liquid allows for the most versatility because bacteria already suspended in liquid could be tested or bacteria could be suspended in liquid from a solid if needed. Different methods of dispensing liquid were tested such as solenoid valves, and different methods of dispenser movements in the X-Y plane around the surface of the petri dishes were tested such as a five-bar mechanism controlled by two rotary motors. It was found that a small solenoid valve in combination with either a five-bar mechanism with two motors or a simple XY stage were both ergonomic and able to provide high-throughput dispensing of bacteria colonies. Based on the devices performance, it can dispense 86 microliter droplets with 8 millimeters of spacing in 69 seconds (1.25 drops per second)