No anomalous supersaturation in ultracold cirrus laboratory experiments

High-altitude cirrus clouds are climatically important: their formation freeze-dries air ascending to the stratosphere to its final value, and their radiative impact is disproportionately large. However, their formation and growth are not fully understood, and multiple in situ aircraft campaigns have observed frequent and persistent apparent water vapor supersaturations of 5 %–25 % in ultracold cirrus (T<205 K), even in the presence of ice particles. A variety of explanations for these observations have been put forth, including that ultracold cirrus are dominated by metastable ice whose vapor pressure exceeds that of hexagonal ice. The 2013 IsoCloud campaign at the Aerosol Interaction and Dynamics in the Atmosphere (AIDA) cloud and aerosol chamber allowed explicit testing of cirrus formation dynamics at these low temperatures. A series of 28 experiments allows robust estimation of the saturation vapor pressure over ice for temperatures between 189 and 235 K, with a variety of ice nucleating particles. Experiments are rapid enough (∼10 min) to allow detection of any metastable ice that may form, as the timescale for annealing to hexagonal ice is hours or longer over the whole experimental temperature range. We show that in all experiments, saturation vapor pressures are fully consistent with expected values for hexagonal ice and inconsistent with the highest values postulated for metastable ice, with no temperature-dependent deviations from expected saturation vapor pressure. If metastable ice forms in ultracold cirrus clouds, it appears to have a vapor pressure indistinguishable from that of hexagonal ice to within about 4.5 %

Lithography-Free Fabrication of Graphene Devices

We have developed a lithography-free, all-dry process for fabricating graphene devices using an ultrathin quartz filament as a shadow mask to avoid possible contamination of graphene during lithographic process. This technique was used to prepare devices for electrical transport as well as planar tunnel junction studies of n-layer graphene (nLG), with n = 1, 2, 3 and higher. We observed localization behavior and an apparent reduction of density of states (DOS) near the Fermi energy in nLG

Bedside nurses\u27 perceptions of effective nurse-physician communication in general medical units: A qualitative study

Background There is a dearth of research on successful interventions to improve nurse-physician communication (NPC). An important step is identifying what matters to bedside nurses and their perceptions of effective NPC communications and actions. Methods We conducted three focus groups with a total of 19 medical unit nurses across two hospitals in one academic medical center in the United States. Using a convenience sampling strategy, five to eight nurses voluntarily participated in each focus group. The recording was transcribed verbatim and two independent coders performed coding and resolved any discrepancies in codes. Qualitative content analysis was pursued to identify themes and associated quotes. Results The presence of direct communication between physicians and nurses was identified as the first theme and perceived by nurses as very important. Additional themes related to physician communication and attributes emerged including collegiality and respect (e.g., engaging nurses as partners in patient care), attentiveness and responsiveness (e.g., listening carefully and addressing concerns), and directness and support (e.g., backing nurses up in difficult situations). Effective NPC is further facilitated by organizational structure, relationship development separate from patient care, and consistent/timely use of technology. Conclusions Hospital bedside nurses provided valuable insight into improved physician communication and what attributes contribute to more effective NPC. Most importantly, they emphasized the significance of physicians in supporting them with difficult patients

Pennsylvania Folklife Vol. 41, No. 1

• Jacob Maentel: A Second Look • The Five-Plate Stove Revisited • The Life and Death of an Appalachian Farm • Henry Harbaugh, Quintessential Dutchman • In Memoriam: William T. Parsons, 1923-1991https://digitalcommons.ursinus.edu/pafolklifemag/1132/thumbnail.jp

Re-evaluating cloud chamber constraints on depositional ice growth in cirrus clouds – Part 1: Model description and sensitivity tests

Ice growth from vapor deposition is an important process for the evolution of cirrus clouds, but the physics of depositional ice growth at the low temperatures (&lt;235 K) characteristic of the upper troposphere and lower stratosphere is not well understood. Surface attachment kinetics, generally parameterized as a deposition coefficient αD, control ice crystal habit and also may limit growth rates in certain cases, but significant discrepancies between experimental measurements have not been satisfactorily explained. Experiments on single ice crystals have previously indicated the deposition coefficient is a function of temperature and supersaturation, consistent with growth mechanisms controlled by the crystal's surface characteristics. Here we use observations from cloud chamber experiments in the Aerosol Interactions and Dynamics in the Atmosphere (AIDA) aerosol and cloud chamber to evaluate surface kinetic models in realistic cirrus conditions. These experiments have rapidly changing temperature, pressure, and ice supersaturation such that depositional ice growth may evolve from diffusion limited to surface kinetics limited over the course of a single experiment. In Part 1, we describe the adaptation of a Lagrangian parcel model with the Diffusion Surface Kinetics Ice Crystal Evolution (DiSKICE) model (Zhang and Harrington, 2014) to the AIDA chamber experiments. We compare the observed ice water content and saturation ratios to that derived under varying assumptions for ice surface growth mechanisms for experiments simulating ice clouds between 180 and 235 K and pressures between 150 and 300 hPa. We found that both heterogeneous and homogeneous nucleation experiments at higher temperatures (&gt;205 K) could generally be modeled consistently with either a constant deposition coefficient or the DiSKICE model assuming growth on isometric crystals via abundant surface dislocations. Lower-temperature experiments showed more significant deviations from any depositional growth model, with different ice growth rates for heterogeneous and homogeneous nucleation experiments.</p

Analysis of the Ex Vivo and In Vivo Antiretroviral Activity of Gemcitabine

Replication of retroviral and host genomes requires ribonucleotide reductase to convert rNTPs to dNTPs, which are then used as substrates for DNA synthesis. Inhibition of ribonucleotide reductase by hydroxyurea (HU) has been previously used to treat cancers as well as HIV. However, the use of HU as an antiretroviral is limited by its associated toxicities such as myelosuppression and hepatotoxicity. In this study, we examined the ribonucleotide reductase inhibitor, gemcitabine, both in cell culture and in C57Bl/6 mice infected with LP-BM5 murine leukemia virus (LP-BM5 MuLV, a murine AIDS model). Gemcitabine decreased infectivity of MuLV in cell culture with an EC50 in the low nanomolar range with no detectable cytotoxicity. Similarly, gemcitabine significantly decreased disease progression in mice infected with LP-BM5. Specifically, gemcitabine treatment decreased spleen size, plasma IgM, and provirus levels compared to LP-BM5 MuLV infected, untreated mice. Gemcitabine efficacy was observed at doses as low as 1 mg/kg/day in the absence of toxicity. Higher doses of gemcitabine (3 mg/kg/day and higher) were associated with toxicity as determined by a loss in body mass. In summary, our findings demonstrate that gemcitabine has antiretroviral activity ex vivo and in vivo in the LP-BM5 MuLV model. These observations together with a recent ex vivo study with HIV-1[1], suggest that gemcitabine has broad antiretroviral activity and could be particularly useful in vivo when used in combination drug therapy

Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

Correction to: Scientific Reports https://doi.org/10.1038/srep29179, published online 14 July 201

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites

SPIRE - combining SGI-110 with cisplatin and gemcitabine chemotherapy for solid malignancies including bladder cancer: study protocol for a phase Ib/randomised IIa open label clinical trial

Background Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer, Cancer Research UK, Accessed 26 Mar 2018). Cisplatin-based chemotherapy is standard of care therapy for UBC for both palliative first-line treatment of advanced/metastatic disease and radical neoadjuvant treatment of localised muscle invasive bladder cancer. However, cisplatin resistance remains a critical cause of treatment failure and a barrier to therapeutic advance in UBC. Based on supportive pre-clinical data, we hypothesised that DNA methyltransferase inhibition would circumvent cisplatin resistance in UBC and potentially other cancers. Methods The addition of SGI-110 (guadecitabine, a DNA methyltransferase inhibitor) to conventional doublet therapy of gemcitabine and cisplatin (GC) is being tested within the phase Ib/IIa SPIRE clinical trial. SPIRE incorporates an initial, modified rolling six-dose escalation phase Ib design of up to 36 patients with advanced solid tumours followed by a 20-patient open-label randomised controlled dose expansion phase IIa component as neoadjuvant treatment for UBC. Patients are being recruited from UK secondary care sites. The dose escalation phase will determine a recommended phase II dose (RP2D, primary endpoint) of SGI-110, by subcutaneous injection, on days 1–5 for combination with GC at conventional doses (cisplatin 70 mg/m2, IV infusion, day 8; gemcitabine 1000 mg/m2, IV infusion, days 8 and 15) in every 21-day cycle. In the dose expansion phase, patients will be randomised 1:1 to GC with or without SGI-110 at the proposed RP2D. Secondary endpoints will include toxicity profiles, SGI-110 pharmacokinetics and pharmacodynamic biomarkers, and pathological complete response rates in the dose expansion phase. Analyses will not be powered for formal statistical comparisons and descriptive statistics will be used to describe rates of toxicity, efficacy and translational endpoints by treatment arm. Discussion SPIRE will provide evidence for whether SGI-110 in combination with GC chemotherapy is safe and biologically effective prior to future phase II/III trials as a neoadjuvant therapy for UBC and potentially in other cancers treated with GC