Method and apparatus for measuring frequency and phase difference

A system for deriving direct digital indications of frequency and phase difference between two incoming pulse trains adaptable for collision avoidance systems or the like. A pair of radar beams 152 and 152A are directed toward a target 153 and corresponding beams 154 and 154A returning therefrom are detected. A digital difference circuit 110 forms a pulse train 66 from the Doppler shift frequencies of each beam pair having a repetition rate functionally related to the difference in magnitude of the shift frequencies. Pulses from the pulse train are counted as a function of time. Visual indications thereof on display 144 are correlative to target position relative to beams 152 and 152A

A noble task: Testing an operational model of clergy occupational health

In many ways, clergy and religious leaders are an ignored yet high-risk population. In their efforts to ensure the spiritual well-being of their congregations, clergy frequently neglect their own well-being, resulting in stress and burnout, which then can lead to impaired health. This neglect often extends to clergy’s family and congregation. Church members typically seek help from clergy to cope with the loss of loved ones, life crises, and other general life stressors. A clergy member unable to cope with these same challenges in his or her own life may be ineffective at helping church members to cope with their stress. Recent theory applications and measure development efforts in this research space have led to several studies of specific occupational hazards or challenges faced by clergy. These challenges include high job demands, congregational criticism, and isolation; restoration following moral failures (e.g., alcohol abuse, adultery); and resolving conflict among congregation members . Furthermore, a holistic model of clergy health functioning has been proposed, which includes specific occupational challenges and their detrimental effects on clergy health. Unfortunately, the constructs in this model are more theoretical than operational. While such a model is useful for conceptualizing the factors that influence clergy health, an operational model of clergy holistic health is still needed to empirically test the effects of occupational demands, and personal and job-related resources on the health of clergy. The purpose of the present study, therefore, is to develop and test such a model. The ultimate goal of this research is to offer a model and methodological approach that can be useful to those interested in better identifying and addressing the health and well-being needs of clergy so that they may thrive in their roles to the betterment of their families and congregations

Mixed Linear/Square-Root Encoded Single Slope Ramp Provides a Fast, Low Noise Analog to Digital Converter with Very High Linearity for Focal Plane Arrays

An analog-to-digital converter (ADC) converts pixel voltages from a CMOS image into a digital output. A voltage ramp generator generates a voltage ramp that has a linear first portion and a non-linear second portion. A digital output generator generates a digital output based on the voltage ramp, the pixel voltages, and comparator output from an array of comparators that compare the voltage ramp to the pixel voltages. A return lookup table linearizes the digital output values

Benzylideneoxymorphone: A New Lead for Development of Bifunctional Mu/Delta Opioid Receptor Ligands

Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands

Uptake, Distribution and Diffusivity of Reactive Fluorophores in Cells: Implications Toward Target Identification

There is much recent interest in the application of copper-free click chemistry to study a wide range of biological events in vivo and in vitro. Specifically, azide-conjugated fluorescent probes can be used to identify targets which have been modified with bioorthogonal reactive groups. For intracellular applications of this chemistry, the structural and physicochemical properties of the fluorescent azide become increasingly important. Ideal fluorophores should extensively accumulate within cells, have even intracellular distribution, and be free (unbound), allowing them to efficiently participate in bimolecular reactions. We report here on the synthesis and evaluation a set of structurally diverse fluorescent probes to examine their potential usefulness in intracellular click reactions. Total cellular uptake and intracellular distribution profiles were comparatively assessed using both quantitative and qualitative approaches. The intracellular diffusion coefficients were measured using a fluorescence recovery after photobleaching (FRAP)-based method. Many reactive fluorophores exhibited suboptimal properties for intracellular reactions. BODIPY- and TAMRA-based azides had superior cellular accumulation, whereas TAMRA-based probes had the most uniform intracellular distribution and best cytosolic diffusivity. Collectively, these results provide an unbiased comparative evaluation regarding the suitability of azide-linked fluorophores for intracellular click reactions

Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A

As part of our continuing efforts toward more fully understanding the structure−activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels−Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure−activity relationships of furan-containing natural products

The Most Massive Ultra-Compact Dwarf Galaxy in the Virgo Cluster

We report on the properties of the most massive ultra-compact dwarf galaxy (UCD) in the nearby Virgo Cluster of galaxies using imaging from the Next Generation Virgo Cluster Survey (NGVS) and spectroscopy from Keck/DEIMOS. This object (M59-UCD3) appears to be associated with the massive Virgo galaxy M59 (NGC 4621), has an integrated velocity dispersion of 78 km/s, a dynamical mass of $3.7\times10^8 M_\odot$, and an effective radius ($R_e$) of 25 pc. With an effective surface mass density of $9.4\times10^{10} M_\odot/kpc^2$, it is the densest galaxy in the local Universe discovered to date, surpassing the density of the luminous Virgo UCD, M60-UCD1. M59-UCD3 has a total luminosity of $M_{g'}=-14.2$ mag, and a spectral energy distribution consistent with an old (14 Gyr) stellar population with [Fe/H]=0.0 and [$\alpha$/Fe]=+0.2. We also examine deep imaging around M59 and find a broad low surface brightness stream pointing towards M59-UCD3, which may represent a tidal remnant of the UCD progenitor. This UCD, along with similar objects like M60-UCD1 and M59cO, likely represents an extreme population of tidally stripped galaxies more akin to larger and more massive compact early-type galaxies than to nuclear star clusters in present-day dwarf galaxies.Comment: 6 pages, 4 figures, 1 table, accepted for publication in ApJ Letter

Sparsely-Bonded CMOS Hybrid Imager

A method and device for imaging or detecting electromagnetic radiation is provided. A device structure includes a first chip interconnected with a second chip. The first chip includes a detector array, wherein the detector array comprises a plurality of light sensors and one or more transistors. The second chip includes a Read Out Integrated Circuit (ROIC) that reads out, via the transistors, a signal produced by the light sensors. A number of interconnects between the ROIC and the detector array can be less than one per light sensor or pixel

The Genome and Methylome of a Beetle with Complex Social Behavior,Nicrophorus vespilloides(Coleoptera: Silphidae)

Testing for conserved and novelmechanisms underlying phenotypic evolution requires a diversity of genomes available for comparisonspanning multiple independent lineages. For example, complex social behavior in insects has been investigated primarily witheusocial lineages, nearly all of which are Hymenoptera. If conserved genomic influences on sociality do exist, we need data from awider range of taxa that also vary in their levels of sociality. Here,we present the assembled and annotated genome of the subsocialbeetle Nicrophorus vespilloides, a species long used to investigate evolutionary questions of complex social behavior. We used thisgenome to address two questions. First, do aspects of life history, such as using a carcass to breed, predict overlap in gene modelsmore strongly than phylogeny? We found that the overlap in gene models was similar between N. vespilloides and all other insectgroups regardless of life history. Second, like other insects with highly developed social behavior but unlike other beetles, doesN. vespilloides have DNA methylation?We found strong evidence for an active DNA methylation system. The distribution of methylationwassimilar to other insects with exons having themostmethylatedCpGs. Methylation status appears highly conserved; 85%of themethylated genes in N. vespilloides are alsomethylated in the hymentopteran Nasonia vitripennis. The addition of this genomeadds a coleopteran resource to answer questions about the evolution and mechanistic basis of sociality and to address questionsabout the potential role of methylation in social behavior

Comparing Breast Cancer Multiparameter Tests in the OPTIMA Prelim Trial: No Test Is More Equal Than the Others

Background: Previous reports identifying discordance between multiparameter tests at the individual patient level have been largely attributed to methodological shortcomings of multiple in silico studies. Comparisons between tests, when performed using actual diagnostic assays, have been predicted to demonstrate high degrees of concordance. OPTIMA prelim compared predicted risk stratification and subtype classification of different multiparameter tests performed directly on the same population. Methods: Three hundred thirteen women with early breast cancer were randomized to standard (chemotherapy and endocrine therapy) or test-directed (chemotherapy if Oncotype DX recurrence score >25) treatment. Risk stratification was also determined with Prosigna (PAM50), MammaPrint, MammaTyper, NexCourse Breast (IHC4-AQUA), and conventional IHC4 (IHC4). Subtype classification was provided by Blueprint, MammaTyper, and Prosigna. Results: Oncotype DX predicted a higher proportion of tumors as low risk (82.1%, 95% confidence interval [CI] = 77.8% to 86.4%) than were predicted low/intermediate risk using Prosigna (65.5%, 95% CI = 60.1% to 70.9%), IHC4 (72.0%, 95% CI = 66.5% to 77.5%), MammaPrint (61.4%, 95% CI = 55.9% to 66.9%), or NexCourse Breast (61.6%, 95% CI = 55.8% to 67.4%). Strikingly, the five tests showed only modest agreement when dichotomizing results between high vs low/intermediate risk. Only 119 (39.4%) tumors were classified uniformly as either low/intermediate risk or high risk, and 183 (60.6%) were assigned to different risk categories by different tests, although 94 (31.1%) showed agreement between four of five tests. All three subtype tests assigned 59.5% to 62.4% of tumors to luminal A subtype, but only 121 (40.1%) were classified as luminal A by all three tests and only 58 (19.2%) were uniformly assigned as nonluminal A. Discordant subtyping was observed in 123 (40.7%) tumors. Conclusions: Existing evidence on the comparative prognostic information provided by different tests suggests that current multiparameter tests provide broadly equivalent risk information for the population of women with estrogen receptor (ER)–positive breast cancers. However, for the individual patient, tests may provide differing risk categorization and subtype information