In vitro antimicrobial activities of novel anilinouracils which selectively inhibit DNA polymerase III of gram-positive bacteria

The 6-anilinouracils are novel dGTP analogs that selectively inhibit the replication-specific DNA polymerase III of gram-positive eubacteria. Two specific derivatives, IMAU (6-[3\u27-iodo-4\u27-methylanilino]uracil) and EMAU (6-[3\u27-ethyl-4\u27-methylanilino]uracil), were substituted with either a hydroxybutyl (HB) or a methoxybutyl (MB) group at their N3 positions to produce four agents: HB-EMAU, MB-EMAU, HB-IMAU, and MB-IMAU. These four new agents inhibited Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Time-kill assays and broth dilution testing confirmed bactericidal activity. These anilinouracil derivatives represent a novel class of antimicrobials with promising activities against gram-positive bacteria that are resistant to currently available agents, validating replication-specific DNA polymerase III as a new target for antimicrobial development

The peripheral blood transcriptome in septic cardiomyopathy: an observational, pilot study.

BACKGROUND:Septic cardiomyopathy (SCM) is common in sepsis and associated with increased morbidity and mortality. Left ventricular global longitudinal strain (LV GLS), measured by speckle tracking echocardiography, allows improved identification of impaired cardiac contractility. The peripheral blood transcriptome may be an important window into SCM pathophysiology. We therefore studied the peripheral blood transcriptome and LV GLS in a prospective cohort of patients with sepsis. RESULTS:In this single-center observational pilot study, we enrolled adult patients (age > 18) with sepsis within 48 h of admission to the ICU. SCM was defined as LV GLS > - 17% based on echocardiograms performed within 72 h of admission. We enrolled 27 patients, 24 of whom had high-quality RNA results; 18 (75%) of 24 had SCM. The group was 50% female and had a median (IQR) age of 59.5 (48.5-67.0) years and admission APACHE II score of 21.0 (16.0-32.3). Forty-six percent had septic shock. After filtering for low-expression and non-coding genes, 15,418 protein coding genes were expressed and 73 had significantly different expression between patients with vs. without SCM. In patients with SCM, 43 genes were upregulated and 30 were downregulated. Pathway analysis identified enrichment in type 1 interferon signaling (adjusted p < 10-5). CONCLUSIONS:In this hypothesis-generating study, SCM was associated with upregulation of genes in the type 1 interferon signaling pathway. Interferons are cytokines that stimulate the innate and adaptive immune response and are implicated in the early proinflammatory and delayed immunosuppression phases of sepsis. While type 1 interferons have not been implicated previously in SCM, interferon therapy (for viral hepatitis and Kaposi sarcoma) has been associated with reversible cardiomyopathy, perhaps suggesting a role for interferon signaling in SCM

Astrophysical factors:Zero energy vs. Most effective energy

Effective astrophysical factors for non-resonant astrophysical nuclear reaction are invariably calculated with respect to a zero energy limit. In the present work that limit is shown to be very disadvantageous compared to the more natural effective energy limit. The latter is used in order to modify the thermonuclear reaction rate formula so that it takes into account both plasma and laboratory screening effects.Comment: 7 RevTex pages. Accepted for publication in Phys.Rev.

Atomic effects in astrophysical nuclear reactions

Two models are presented for the description of the electron screening effects that appear in laboratory nuclear reactions at astrophysical energies. The two-electron screening energy of the first model agrees very well with the recent LUNA experimental result for the break-up reaction $He3(He3,2p)He^{4}$, which so far defies all available theoretical models. Moreover, multi-electron effects that enhance laboratory reactions of the CNO cycle and other advanced nuclear burning stages, are also studied by means of the Thomas-Fermi model, deriving analytical formulae that establish a lower and upper limit for the associated screening energy. The results of the second model, which show a very satisfactory compatibility with the adiabatic approximation ones, are expected to be particularly useful in future experiments for a more accurate determination of the CNO astrophysical factors.Comment: 14 RevTex pages + 2 ps (revised) figures. Phys.Rev.C (in production

A Retrospective Study of the Investigation of Homicidal Childhood Asphyxial Deaths

As one of the leading causes of traumatic deaths in newborns, infants, and young children, there is no anatomic or microscopic feature that is pathognomonic for asphyxial deaths. Instead, pathologists rely on investigation information, including confessions and/or witness statements, and potential evidence at the scene. Twenty cases of homicidal newborn, infant, and young children asphyxial deaths were reviewed, which included death and police investigation reports and autopsy reports, as well as histology slides of lung sections. This series of homicidal asphyxial deaths highlight that, in a vast majority of such cases, the final cause and manner of death rulings are dependent on confession by the perpetrator. Furthermore, this series highlights the possible role of histology to help forensic pathologists better certify asphyxial deaths. Finally, this series emphasizes important investigation points and considerations at autopsy during the investigation of asphyxial deaths in newborns, infants, and young children.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144651/1/jfo13666_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144651/2/jfo13666.pd

Encoding a magic state with beyond break-even fidelity

We distill magic states to complete a universal set of fault-tolerant logic gates that is needed for large-scale quantum computing. By encoding better quality input states for our distillation procedure, we can reduce the considerable resource cost of producing magic states. We demonstrate an error-suppressed encoding scheme for a two-qubit input magic state, that we call the CZ state, on an array of superconducting qubits. Using a complete set of projective logical Pauli measurements, that are also tolerant to a single circuit error, we propose a circuit that demonstrates a magic state prepared with infidelity $(1.87 \pm 0.16) \times 10^{-2}$. Additionally, the yield of our scheme increases with the use of adaptive circuit elements that are conditioned in real time on mid-circuit measurement outcomes. We find our results are consistent with variations of the experiment, including where we use only post-selection in place of adaptive circuits, and where we interrogate our output state using quantum state tomography on the data qubits of the code. Remarkably, the error-suppressed preparation experiment demonstrates a fidelity exceeding that of the preparation of the same unencoded magic-state on any single pair of physical qubits on the same device.Comment: 10 pages, 7 figures, comments welcom

The Ursinus Weekly, November 15, 1973

First SFARC meeting yields suggestions for parking, Wismer • Banana split rated big success as news spreads across the country • Philadelphia soloists will play at forum • Career day planned for English majors • New Sturgis portrait dedicated at ceremony • Editorial: All that shivers is not cold • Spotlight: Mr. Scott Dempsey • Letters to the editor: SFARC member pledges interest; Faculty digs banana split • Alumni corner: U.C. graduate now holds position as ambassador • Tolstoy’s War and peace to be shown on PBS starting next Tuesday • Jazz: Buddy Rich strikes out • Believe it or not • A splendid time was guaranteed for all • The Zodiac: A preview to real astrology • Guard hired to check I.D.’s during open dorms • Ursinus women athletes make better lovers • Booters stand 6-6-1 • X-country wrap-up • Bears upset Grove Cityhttps://digitalcommons.ursinus.edu/weekly/1006/thumbnail.jp

Discovering hidden relationships between renal diseases and regulated genes through 3D network visualizations

Abstract Background In a recent study, two-dimensional (2D) network layouts were used to visualize and quantitatively analyze the relationship between chronic renal diseases and regulated genes. The results revealed complex relationships between disease type, gene specificity, and gene regulation type, which led to important insights about the underlying biological pathways. Here we describe an attempt to extend our understanding of these complex relationships by reanalyzing the data using three-dimensional (3D) network layouts, displayed through 2D and 3D viewing methods. Findings The 3D network layout (displayed through the 3D viewing method) revealed that genes implicated in many diseases (non-specific genes) tended to be predominantly down-regulated, whereas genes regulated in a few diseases (disease-specific genes) tended to be up-regulated. This new global relationship was quantitatively validated through comparison to 1000 random permutations of networks of the same size and distribution. Our new finding appeared to be the result of using specific features of the 3D viewing method to analyze the 3D renal network. Conclusions The global relationship between gene regulation and gene specificity is the first clue from human studies that there exist common mechanisms across several renal diseases, which suggest hypotheses for the underlying mechanisms. Furthermore, the study suggests hypotheses for why the 3D visualization helped to make salient a new regularity that was difficult to detect in 2D. Future research that tests these hypotheses should enable a more systematic understanding of when and how to use 3D network visualizations to reveal complex regularities in biological networks.http://deepblue.lib.umich.edu/bitstream/2027.42/112972/1/13104_2010_Article_700.pd

SOURCES 4C : a code for calculating ([alpha],n), spontaneous fission, and delayed neutron sources and spectra.

SOURCES 4C is a computer code that determines neutron production rates and spectra from ({alpha},n) reactions, spontaneous fission, and delayed neutron emission due to radionuclide decay. The code is capable of calculating ({alpha},n) source rates and spectra in four types of problems: homogeneous media (i.e., an intimate mixture of a-emitting source material and low-Z target material), two-region interface problems (i.e., a slab of {alpha}-emitting source material in contact with a slab of low-Z target material), three-region interface problems (i.e., a thin slab of low-Z target material sandwiched between {alpha}-emitting source material and low-Z target material), and ({alpha},n) reactions induced by a monoenergetic beam of {alpha}-particles incident on a slab of target material. Spontaneous fission spectra are calculated with evaluated half-life, spontaneous fission branching, and Watt spectrum parameters for 44 actinides. The ({alpha},n) spectra are calculated using an assumed isotropic angular distribution in the center-of-mass system with a library of 107 nuclide decay {alpha}-particle spectra, 24 sets of measured and/or evaluated ({alpha},n) cross sections and product nuclide level branching fractions, and functional {alpha}-particle stopping cross sections for Z < 106. The delayed neutron spectra are taken from an evaluated library of 105 precursors. The code provides the magnitude and spectra, if desired, of the resultant neutron source in addition to an analysis of the'contributions by each nuclide in the problem. LASTCALL, a graphical user interface, is included in the code package

A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness

Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n ¼ 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) mm/year] than DRV/r [12.9 (10.3, 15.5) mm/year, P ¼ 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) mm/year, P ¼ 0.15 vs. ATV/r; P ¼ 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia