Microwave nonlinearity and photoresponse of superconducting resonators with columnar defect micro-channels

NASA Astrophysics Data System (ADS)

Remillard, S. K.; Kirkendall, D.; Ghigo, G.; Gerbaldo, R.; Gozzelino, L.; Laviano, F.; Yang, Z.; Mendelsohn, N. A.; Ghamsari, B. G.; Friedman, B.; Jung, P.; Anlage, S. M.

2014-09-01

Micro-channels of nanosized columnar tracks were planted by heavy-ion irradiation into superconducting microwave microstrip resonators that were patterned from YBa2Cu3O7 - x thin films on LaAlO3 substrates. Three different ion fluences were used, producing different column densities, with each fluence having a successively greater impact on the microwave nonlinearity of the device, as compared to a control sample. Photoresponse (PR) images made with a 638 nm rastered laser beam revealed that the channel is a location of enhanced PR and a hot spot for the generation of intermodulation distortion. The microwave PR technique was also advanced in this work by investigating the role of coupling strength on the distribution of PR between inductive and resistive components.

The use of permeation tube device and the development of empirical formula for accurate permeation rate

USDA-ARS?s Scientific Manuscript database

A series of laboratory experiments were conducted to assess the accuracy of permeation tube (PT) devices using a calibration gas generator system to measure permeation rate (PR) of volatile organic compounds (VOCs). Calibration gas standards of benzene, toluene, and m-xylene (BTX) were produced from...

The performance characteristics of lateral flow devices with 2 strains of highly pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Lateral flow devices (LFD) are commercially available and provide a fast, highly specific, on-site test for avian influenza. Because of the low analytic sensitivity of LFD tests at low virus concentrations, targeted sampling of sick and dead birds has been proposed in order to increase detection pr...

Air Pollution Tests Using the "DEMA"

ERIC Educational Resources Information Center

Wilt, L. M.

1970-01-01

Describes the making and calibrating of a DEMA (DEvice for Measuring Air) from readily available, inexpensive materials. Procedures for measuring atmospheric particulates, acids, and carbon monoxide are described. (PR)

Photoluminescence Properties of Ca3Si2O7: Pr3+ Orange-Red Phosphors Prepared by High-Temperature Solid-State Method

NASA Astrophysics Data System (ADS)

Peng, Zhi-Qing; Chen, Rong; Feng, Wen-Lin

2018-06-01

Novel luminescent materials Ca3-xSi2O7: xPr3+ were successfully prepared by the high-temperature solid-state method. The crystal structure, morphology, and optical spectrum were characterised by X-ray diffraction (XRD), scanning electron microscopy (SEM), and spectroscopy, respectively. The XRD patterns of the samples indicate that the crystal structure is monoclinic symmetry. The SEM shows that the selected sample has good crystallinity although its appearance is irregular and scalelike. The peak of the excitation spectrum of the sample is located at around 449 nm, corresponding to 3H4→3P2 transition of Pr3+. The peak of the emission spectrum of the sample is situated at around 612 nm which is attributed to 3P0→3H6 transition of Pr3+, and the colour is orange-red. The optimum concentration for Pr3+ replaced Ca2+ sites in Ca3Si2O7: Pr3+ is 0.75 mol%. The lifetime (8.48 μs) of a typical sample (Ca2.9925Pr0.0075)Si2O7 is obtained. It reveals that orange-red phosphors Ca3-xSi2O7: xPr3+ possess remarkable optical properties and can be used in white light emitting devices.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Yongbin; Jia, Yanmin, E-mail: wuzheng@zjnu.cn, E-mail: ymjia@zjnu.edu.cn; Wu, Jiang

A mutual enhancement action between the ferro-/piezoelectric polarization and the photoluminescent performance of rare earth Pr{sup 3+} doped (K{sub 0.5}Na{sub 0.5})NbO{sub 3} (KNN) lead-free ceramics is reported. After Pr{sup 3+} doping, the KNN ceramics exhibit the maximum enhancement of ∼1.2 times in the ferroelectric remanent polarization strength and ∼1.25 times in the piezoelectric coefficient d{sub 33}, respectively. Furthermore, after undergoing a ferro-/piezoelectric polarization treatment, the maximum enhancement of ∼1.3 times in photoluminescence (PL) was observed in the poled 0.3% Pr{sup 3+} doped sample. After the trivalent Pr{sup 3+} unequivalently substituting the univalent (K{sub 0.5}Na{sub 0.5}){sup +}, A-sites ionic vacancies willmore » occur to maintain charge neutrality, which may reduce the inner stress and ease the domain wall motions, yielding to the enhancement in ferro-/piezoelectric performance. The polarization-induced enhancement in PL is attributed to the decrease of crystal symmetry abound the Pr{sup 3+} ions after polarization. The dual-enhancement of the ferro-/piezoelectric and photoluminescent performance makes the Pr{sup 3+} doped KNN ceramic hopeful for piezoelectric/luminescent multifunctional devices.« less

Electromyographic analysis of the masseter and buccinator muscles with the pro-fono facial exerciser use in bruxers.

PubMed

Jardini, Renata S R; Ruiz, Lydia S R; Moysés, Maria A A

2006-01-01

The aim of this study was to evaluate the efficiency of the Pró-Fono Facial Exerciser (Pró-Fono Productos Especializados para Fonoaudiologia Ltda., Barueri/SP, Brazil) to decrease bruxism, as well as the correlation between the masseter and the buccinator muscles using electromyography (EMG). In this study, 39 individuals ranging from 23 to 48 years of age were selected from a dental school and then underwent surface EMG at three different periods of time: 0, 10, and 70 days. They were divided into a normal control group, a bruxer control group (without device), and an experimental bruxer group who used the device. The bruxer group showed a greater masseter EMG amplitude when compared to the normal group, while the experimental group had deceased activity with a reduction in symptoms. The buccinator EMG spectral analysis of the experimental bruxist group showed asynchronous contractions of the masseter muscle (during jaw opening) after using the Pró-Fono Facial Exerciser. The normal group also showed asynchronous contractions. Upon correlation of the data between these muscles, the inference is that there is a reduction in bruxism when activating the buccinator muscle.

Supporting narrative retells for people with aphasia using augmentative and alternative communication: photographs or line drawings? Text or no text?

PubMed

Griffith, Julie; Dietz, Aimee; Weissling, Kristy

2014-05-01

The purpose of this study was to examine how the interface design of an augmentative and alternative communication (AAC) device influences the communication behaviors of people with aphasia during a narrative retell task. A case-series design was used. Four narratives were created on an AAC device with combinations of personally relevant (PR) photographs, line drawings (LDs), and text for each participant. The narrative retells were analyzed to describe the expressive modality units (EMUs) used, trouble sources experienced, and whether trouble sources were repaired. The researchers also explored the participants' perceived helpfulness of the interface features. The participants primarily used spoken EMUs to retell their narratives. They relied on PR photographs more frequently than LDs; however, they reported both picture types to be equally helpful. Text was frequently used and reported as helpful by all 4 people with aphasia. Participants experienced similar rates of trouble sources across conditions; however, they displayed unique trends for successful repairs of trouble sources. For narrative retells, LDs may serve as an effective visual support when PR photographs are unavailable. Individual assessment is necessary to determine the optimum combination of supports in AAC systems for people with aphasia.

Improved ferroelectric and photoluminescence properties in Pr3+ substituted Na0.5Bi0.5TiO3 synthesized using hydrothermal route

NASA Astrophysics Data System (ADS)

Goutham, Cilaveni; Kandula, Kumara Raja; Raavi, Sai Santhosh Kumar; Asthana, Saket

2018-04-01

Nanocrystalline Pr3+ substituted NBT was synthesized using hydrothermal technique. Pr3+ modifies the ferroelectric NBT optically active and enhances the electrical properties with small structural changes. Aiming to the development of the bottom up optoelectronic devices this optimized nanoscale Na0.5Bi0.5-xPrxTiO3(x = 0.005) compound is synthesized hydrothermally. X-ray diffraction pattern shows that the system is stabilized in the Rhombohedral (space groupR3c) phase indicating the local strain inhomogeneity. PE loop shows that there is a decrement in the Ec value compared with compounds synthesized using conventional methods. The strong red emission assigned to prominent transition of the Pr3+ ions at 610nm was observed along with weak blue-green emission, indicating the potential use of the system. Energy transfer from host system to Pr3+ ions is responsible for red emission while blue green emission is due to quenching of 3P0 induced by intervalence charge transfer state.

Improving Pulse Rate Measurements during Random Motion Using a Wearable Multichannel Reflectance Photoplethysmograph.

PubMed

Warren, Kristen M; Harvey, Joshua R; Chon, Ki H; Mendelson, Yitzhak

2016-03-07

Photoplethysmographic (PPG) waveforms are used to acquire pulse rate (PR) measurements from pulsatile arterial blood volume. PPG waveforms are highly susceptible to motion artifacts (MA), limiting the implementation of PR measurements in mobile physiological monitoring devices. Previous studies have shown that multichannel photoplethysmograms can successfully acquire diverse signal information during simple, repetitive motion, leading to differences in motion tolerance across channels. In this paper, we investigate the performance of a custom-built multichannel forehead-mounted photoplethysmographic sensor under a variety of intense motion artifacts. We introduce an advanced multichannel template-matching algorithm that chooses the channel with the least motion artifact to calculate PR for each time instant. We show that for a wide variety of random motion, channels respond differently to motion artifacts, and the multichannel estimate outperforms single-channel estimates in terms of motion tolerance, signal quality, and PR errors. We have acquired 31 data sets consisting of PPG waveforms corrupted by random motion and show that the accuracy of PR measurements achieved was increased by up to 2.7 bpm when the multichannel-switching algorithm was compared to individual channels. The percentage of PR measurements with error ≤ 5 bpm during motion increased by 18.9% when the multichannel switching algorithm was compared to the mean PR from all channels. Moreover, our algorithm enables automatic selection of the best signal fidelity channel at each time point among the multichannel PPG data.

Development of a new magnetocaloric material used in a magnetic refrigeration device

NASA Astrophysics Data System (ADS)

Guillou, F.; Legait, U.; Kedous-Lebouc, A.; Hardy, V.

2012-06-01

Testing directly a magnetocaloric material in a magnetic refrigeration (MR) system is the best way to judge of its applicative potentialities. In this spirit, an oxide expected to show promising magnetocaloric properties around room temperature (Pr0.65Sr0.35MnO3) was produced in large scale and shaped in order to build a regenerator. Magnetization, heat capacity, resistivity, thermal conductivity and a direct test in a MR device were carried out on this manganite. The results were compared to those observed in the reference material which is Gadolinium. The two main conclusions of these preliminary results are: (i) the Pr0.65Sr0.35MnO3 actually displays not only a significant magnetocaloric effect but also a real refrigeration capability at room temperature; (ii) the temperature spans reached in these first experiments are even found to well compare with those obtained with Gd.

Subepidermal moisture detection of heel pressure injury: The pressure ulcer detection study outcomes.

PubMed

Bates-Jensen, Barbara M; McCreath, Heather E; Nakagami, Gojiro; Patlan, Anabel

2018-04-01

We examined subepidermal moisture (SEM) and visual skin assessment of heel pressure injury (PrI) among 417 nursing home residents in 19 facilities over 16 weeks. Participants were older (mean age 77 years), 58% were female, over half were ethnic minorities (29% African American, 12% Asian American, 21% Hispanic), and at risk for PrI (mean Braden Scale Risk score = 15.6). Blinded concurrent visual assessments and SEM measurements were obtained at heels weekly. Visual skin damage was categorised as normal, erythema, stage 1 PrI, deep tissue injury (DTI) or stage 2 or greater PrI. PrI incidence was 76%. Off-loading occurred with pillows (76% of residents) rather than heel boots (21%) and often for those with DTI (91%). Subepidermal moisture was measured with a device where higher readings indicate greater moisture (range: 0-70 tissue dielectric constant), with normal skin values significantly different from values in the presence of skin damage. Subepidermal moisture was associated with concurrent damage and damage 1 week later in generalised multinomial logistic models adjusting for age, diabetes and function. Subepidermal moisture detected DTI and differentiated those that resolved, remained and deteriorated over 16 weeks. Subepidermal moisture may be an objective method for detecting PrI. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Methodology in the measurement of complex human performance : two-dimensional compensatory tracking.

DOT National Transportation Integrated Search

1972-05-01

Nineteen subjects were tested on two successive days on a complex performance device designed to measure functions of relevance to aircrew performance; included were measures of monitoring, information processing, pattern discrimination, and group pr...

Subepidermal moisture surrounding pressure ulcers in persons with a spinal cord injury: A pilot study

PubMed Central

Harrow, Jeffrey John; Mayrovitz, Harvey N.

2014-01-01

Objective Characterization of a non-invasive method of quantifying subepidermal moisture (SEM) surrounding stages III and IV pressure ulcers (PrUs) in spinal cord injury (SCI). Design Prospective, single-visit, single-rater, observational study, using repeated-measures analysis. Method Setting-inpatient units of one VA SCI Center. Participants Convenience sample of 16 subjects with SCI with stage III or IV PrUs over sacrum or ischium. Interventions Measurement with the MoistureMeter-D, a hand-held device using 300 MHz electromagnetic waves. Outcome measures Dielectric constant, a dimensionless number which increases with the moisture content. Each subject had a PrU site and a control site. Measurements were made at each site, on intact skin, at four points spaced angularly around the site, in triplicate. Results (1) Short-term, single-rater relative error was 2.5%. (2) Order effect: first readings were higher than second readings in 55 of 64 measurement sets. Order effect was significant for control sites (P < 0.0001) but not for PrU sites. (3) Angular effect: SEM varied by angle at the PrU sites (P < 0.01); 12 o'clock position the highest and 6 o'clock the lowest. (4) Ability to differentiate PrUs from intact skin: SEM at PrU sites was greater by 9.0% than control sites (P < 0.05). (5) Site effect: SEM was higher at sacral locations than ischial at control sites by 20% (P < 0.005). Conclusions SEM differentiates PrUs from intact skin. Future study designs must take into account order, angular, and site effects on this measure. This information will inform designers of future studies of SEM in healing of PrUs. PMID:25398030

Microstructure and optical properties of TiO2 nanocrystallites-CaTiO3:Pr3+ hybrid thick films

NASA Astrophysics Data System (ADS)

Xia, Chang-Kui; Gao, Xiang-Dong; Yu, Changjiang; Yu, Aimin; Li, Xiaomin; Gao, Dongsheng; Shi, Ying

Long afterglow CaTiO3:Pr3+ ceramic powders were integrated with hydrothermal TiO2 nanocrystallites via “doctor-blade” and TiO2-CaTiO3:Pr3+ hybrid thick films on FTO substrate were fabricated. Effects of the Pr3+ doping level (0.06%, 0.3%) and the CaTiO3:Pr3+/TiO2 weight ratio (0.23, 0.92) on the crystallinity, morphologies, optical transmittance and photoluminescence (PL) properties were investigated. Results showed that the crystallinity of the hybrid films originated from both TiO2 nanocrystallites and CaTiO3:Pr3+ ceramic particles, affected little by the integrating process. The film surface became denser and coarser due to the incorporation of CaTiO3:Pr3+ micron/submicron particles, and the film thickness varied little (˜2.2μm). The optical transmittance of the hybrid film decreased sharply (<20% for 0.92 incorporation level) due to the scattering effects of the CaTiO3:Pr3+ micron/submicron particles to the incident light. All the hybrid films exhibited strong PL at ˜613nm when excited with 332-335nm, and the film with the Ca0.997TiO3:Pr0.0033+/TiO2 weight ratio of 0.23 showed the highest emission. In addition, the film exhibited a photoresponce to a broad ultraviolet excitation ranging from 288-369nm and a long emission decay time up to 30min at 613nm, possible for use in the ultraviolet detectors, solar cells and other photoelectrical devices.

Effect of Pr3+doping on key properties of CdO thin films deposited by spray pyrolysis using perfume atomizer

NASA Astrophysics Data System (ADS)

Ravikumar, M.; Chandramohan, R.; Kumar, K. Deva Arun; Valanarasu, S.; Kathalingam, A.; Ganesh, V.; Shkir, Mohd.; AlFaify, S.; Algarni, H.

2018-07-01

High quality Cadmium oxide thin films doped with Praseodymium (Pr) were prepared using perfume atomizer based spray pyrolysis technique at substrate temperature near 350 °C. Structural analysis of films was examined by XRD and confirmed that the films are cubic in structure. All un-doped and doped films were good crystalline in nature with smooth and flat surface without significant modifications owed to doping. Optical transmittances of doped films was decrease in the visible and IR range with increasing Pr doping concentration. Band gap widened from 2.42 to 2.20 eV when doped with Pr from 0 to 5 at. %. In addition, the photoluminescence property of the films was also observed. Further, the electrical studies were performed on pure and doped samples Viz., the electrical resistivity, carrier concentration (ρ) and Hall mobility (μ). It confirmed that the deposited films has good structural environments in terms of grain size, absolute stress correspond and low resistivity. Current-voltage measurements on the nanostructured Al/Pr-nCdO/p-Si/Al device showed a non-linear electric characteristics indicating diode like behavior.

Controlled Crystal Grain Growth in Mixed Cation-Halide Perovskite by Evaporated Solvent Vapor Recycling Method for High Efficiency Solar Cells.

PubMed

Numata, Youhei; Kogo, Atsushi; Udagawa, Yosuke; Kunugita, Hideyuki; Ema, Kazuhiro; Sanehira, Yoshitaka; Miyasaka, Tsutomu

2017-06-07

We developed a new and simple solvent vapor-assisted thermal annealing (VA) procedure which can reduce grain boundaries in a perovskite film for fabricating highly efficient perovskite solar cells (PSCs). By recycling of solvent molecules evaporated from an as-prepared perovskite film as a VA vapor source, named the pot-roast VA (PR-VA) method, finely controlled and reproducible device fabrication was achieved for formamidinium (FA) and methylammonium (MA) mixed cation-halide perovskite (FAPbI 3 ) 0.85 (MAPbBr 3 ) 0.15 . The mixed perovskite was crystallized on a low-temperature prepared brookite TiO 2 mesoporous scaffold. When exposed to very dilute solvent vapor, small grains in the perovskite film gradually unified into large grains, resulting in grain boundaries which were highly reduced and improvement of photovoltaic performance in PSC. PR-VA-treated large grain perovskite absorbers exhibited stable photocurrent-voltage performance with high fill factor and suppressed hysteresis, achieving the best conversion efficiency of 18.5% for a 5 × 5 mm 2 device and 15.2% for a 1.0 × 1.0 cm 2 device.

Upconversion luminescence in BaMoO{sub 4}:Pr{sup 3+} phosphor for display devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soni, Abhishek Kumar; Rai, Vineet Kumar, E-mail: vineetkrrai@yahoo.co.in

2015-08-28

The frequency upconversion is an important nonlinear optical property by which near infrared light is converted into the visible light. The BaMoO{sub 4}:Pr{sup 3+} powder phosphor has been synthesized by solid state reaction method. The upconversion emission bands are recorded under the excitation of 808 nm diode laser. The phase formation of the prepared phosphor has been identified by powder X-ray diffraction (XRD) technique. The upconversion emission mechanism and colour coordinate have been explained by using energy level and CIE (International Commission on Illumination) chromaticity diagram study, respectively.

Nitrogen-doped partially reduced graphene oxide rewritable nonvolatile memory.

PubMed

Seo, Sohyeon; Yoon, Yeoheung; Lee, Junghyun; Park, Younghun; Lee, Hyoyoung

2013-04-23

As memory materials, two-dimensional (2D) carbon materials such as graphene oxide (GO)-based materials have attracted attention due to a variety of advantageous attributes, including their solution-processability and their potential for highly scalable device fabrication for transistor-based memory and cross-bar memory arrays. In spite of this, the use of GO-based materials has been limited, primarily due to uncontrollable oxygen functional groups. To induce the stable memory effect by ionic charges of a negatively charged carboxylic acid group of partially reduced graphene oxide (PrGO), a positively charged pyridinium N that served as a counterion to the negatively charged carboxylic acid was carefully introduced on the PrGO framework. Partially reduced N-doped graphene oxide (PrGODMF) in dimethylformamide (DMF) behaved as a semiconducting nonvolatile memory material. Its optical energy band gap was 1.7-2.1 eV and contained a sp2 C═C framework with 45-50% oxygen-functionalized carbon density and 3% doped nitrogen atoms. In particular, rewritable nonvolatile memory characteristics were dependent on the proportion of pyridinum N, and as the proportion of pyridinium N atom decreased, the PrGODMF film lost memory behavior. Polarization of charged PrGODMF containing pyridinium N and carboxylic acid under an electric field produced N-doped PrGODMF memory effects that followed voltage-driven rewrite-read-erase-read processes.

Updateable 3D Display Using Large Area Photorefractive Polymer Devices

DTIC Science & Technology

2013-04-01

across the thin PR layer. The critical parameters for the buffer layer are: transparent over the range 400nm to 800nm, high dielectric strength , ease of...Holographic 3D Display for Telepresence". Holo- pack.Holo- print 2011, November 9th 2011, (Las-Vegas, NV).  J. Thomas et al., "Recent advances in...AFRL-OSR-VA-TR-2013-0199 Updateable 3D Display Using Large Area Photofractive Polymer Devics Pierre Alexandre Blanche TIPD

PRN 99-1: Import of Unregistered Pesticides Intended for Export

EPA Pesticide Factsheets

This PR notice clarifies EPA's interpretation of the scope of the FIFRA Section 17 (a)(1) for import of unregistered pesticides, devices or pesticide active ingredients when the importation is solely for the purpose of formulation or packaging for export.

Effect of warning devices on curve operating speeds.

DOT National Transportation Integrated Search

2005-08-01

The objective of this study is to evaluate the use of several warning signs and warning methods to identify those that have the greatest impact on reducing vehicle speeds when traversing a horizontal curve. Three sites were selected from a list of pr...

Real-time display of flow-pressure-volume loops.

PubMed

Morozoff, P E; Evans, R W

1992-01-01

Graphic display of respiratory waveforms can be valuable for monitoring the progress of ventilated patients. A system has been developed that can display flow-pressure-volume loops as derived from a patient's respiratory circuit in real time. It can also display, store, print, and retrieve ventilatory waveforms. Five loops can be displayed at once: current, previous, reference, "ideal," and previously saved. Two components, the data-display device (DDD) and the data-collection device (DCD), comprise the system. An IBM 286/386 computer with a graphics card (VGA) and bidirectional parallel port is used for the DDD; an eight-bit microprocessor card and an A/D convertor card make up the DCD. A real-time multitasking operating system was written to control the DDD, while the DCD operates from in-line assembly code. The DCD samples the pressure and flow sensors at 100 Hz and looks for a complete flow waveform pattern based on flow slope. These waveforms are then passed to the DDD via the mutual parallel port. Within the DDD a process integrates the flow to create a volume signal and performs a multilinear regression on the pressure, flow, and volume data to calculate the elastance, resistance, pressure offset, and coefficient of determination. Elastance, resistance, and offset are used to calculate Pr and Pc where: Pr[k] = P[k]-offset-(elastance.V[k]) and Pc[k] = P[k]-offset-(resistance.F[k]). Volume vs. Pc and flow vs. Pr can be displayed in real time. Patient data from previous clinical tests were loaded into the device to verify the software calculations. An analog waveform generator was used to simulate flow and pressure waveforms that validated the system.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced Mixed Electronic-Ionic Conductors through Cation Ordering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobson, Allan J.; Morgan, Dane; Grey, Clare

2014-08-31

The performance of many energy conversion and storage devices depend on the properties of mixed ionic-electronic conducting (miec) materials. Mixed or ambipolar conductors simultaneously transport ions and electrons and provide the critical interface between chemical and electrical energy in devices such as fuel cells, ion transport membranes, and batteries. Enhancements in storage capacity, reversibility, power density and device lifetime all require new materials and a better understanding of the fundamentals of ambipolar conductivity and surface reactivity.The high temperature properties of the ordered perovksites AA’B 2O 5+x, where A = rare earth ion, Y and B = Ba, Sr were studied.more » The work was motivated by the high oxygen transport and surface exchange rates observed for members of this class of mixed ionic and electronic conductors. A combined experimental and computational approach, including structural, electrochemical, and transport characterization and modeling was used. The approach attacks the problem simultaneously at global (e.g., neutron diffraction and impedance spectroscopy), local (e.g., pair distribution function, nuclear magnetic resonance) and molecular (ab initio thermokinetic modeling) length scales. The objectives of the work were to understand how the cation and associated anion order lead to exceptional ionic and electronic transport properties and surface reactivity in AA’B2O5+x perovskites. A variety of compounds were studied by X-ray and neutron diffraction, measurements of thermodynamics and transport and theoretically. These included PrBaCo 2O 5+x and NdBaCo 2O 5+x, PrBaCo 2-xFexO 6- δ (x = 0, 0.5, 1.0, 1.5 and 2) and LnBaCoFeO 6- δ (Ln = La, Pr, Nd, Sm, Eu and Gd), Sr 3YCo 4O 10.5, YBaMn 2O 5+x. A 0.5A’ 0.5BO 3 (where A=Y, Sc, La, Ce, Pr, Nd, Pm, Sm; A’= Sr, Ba; and B= Fe, Co, Mn, Ni), Ba 2In 2O 5, and La 1 xSr xCoO 3-δ /(La 1-ySry) 2CoO 4±δ interfaces.« less

Association of cardiac implantable electronic devices with survival in bifascicular block and prolonged PR interval on electrocardiogram.

PubMed

Moulki, Naeem; Kealhofer, Jessica V; Benditt, David G; Gravely, Amy; Vakil, Kairav; Garcia, Santiago; Adabag, Selcuk

2018-06-16

Bifascicular block and prolonged PR interval on the electrocardiogram (ECG) have been associated with complete heart block and sudden cardiac death. We sought to determine if cardiac implantable electronic devices (CIED) improve survival in these patients. We assessed survival in relation to CIED status among 636 consecutive patients with bifascicular block and prolonged PR interval on the ECG. In survival analyses, CIED was considered as a time-varying covariate. Average age was 76 ± 9 years, and 99% of the patients were men. A total of 167 (26%) underwent CIED (127 pacemaker only) implantation at baseline (n = 23) or during follow-up (n = 144). During 5.4 ± 3.8 years of follow-up, 83 (13%) patients developed complete or high-degree atrioventricular block and 375 (59%) died. Patients with a CIED had a longer survival compared to those without a CIED in the traditional, static analysis (log-rank p < 0.0001) but not when CIED was considered as a time-varying covariate (log-rank p = 0.76). In the multivariable model, patients with a CIED had a 34% lower risk of death (hazard ratio 0.66, 95% confidence interval 0.52-0.83; p = 0.001) than those without CIED in the traditional analysis but not in the time-varying covariate analysis (hazard ratio 1.05, 95% confidence interval 0.79-1.38; p = 0.76). Results did not change in the subgroup with a pacemaker only. Bifascicular block and prolonged PR interval on ECG are associated with a high incidence of complete atrioventricular block and mortality. However, CIED implantation does not have a significant influence on survival when time-varying nature of CIED implantation is considered.

Detection of crestal radiolucencies around dental implants: an in vitro experimental study.

PubMed

Sirin, Yigit; Horasan, Sinan; Yaman, Duygu; Basegmez, Cansu; Tanyel, Cem; Aral, Ali; Guven, Koray

2012-07-01

The aim of this study was to compare the diagnostic potentials and practical advantages of different imaging modalities in detecting bone defects around dental implants. Crestal bone defects with sequentially larger diameters were randomly prepared around 100 implants that were inserted in bovine bone blocks. Conventional periapical radiography (PR), direct digital radiography (DDR), panoramic radiography (PANO), cone-beam computed tomography (CBCT), and multislice computed tomography (MSCT) were performed for all specimens. The diagnostic accuracies of the devices, confidence of the answers, subjective image quality, defect visibility in planar orientations, and duration of diagnosis were analyzed based on the interpretations of 7 calibrated observers. The agreement levels of intra- and interobserver scores were rated good. PR, DDR, and CBCT were mostly more accurate than PANO and MSCT (P < .05). Confidence levels were positively correlated with the defect size (ρ = 0.20, P < .01), and that of DDR was the highest (P < .05). The subjective image quality of PR and DDR was higher than that of CBCT, PANO, and MSCT (P < .05 for all comparisons). Axial-coronal-sagittal visibilities of the defects were higher for CBCT compared with MSCT (P < .05). The diagnostic time was shorter for DDR (P < .05) and longer for the tomographic systems (P < .05) than for the other devices. DDR may provide a faster and more confident diagnostic option that is as accurate as PR in detecting peri-implant radiolucencies. CBCT has a comparable potential to these intraoral systems but with slower decision making and lower image quality, whereas PANO and MSCT become more reliable when bone defects have a diameter that is at least 1.5 mm larger than that of the implant. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

In-line polarization rotator based on the quantum-optical analogy.

PubMed

Chen, Lei; Qu, Ke-Nan; Shen, Heng; Zhang, Wei-Gang; Chou, Keng C; Liu, Qian; Yan, Tie-Yi; Wang, Biao; Wang, Song

2016-05-01

An in-line polarization rotator (PR) is proposed based on the quantum-optical analogy (QOA). The proposed PR possesses an auxiliary E7 liquid crystal (LC) waveguide in the vicinity of the single-mode fiber (SMF) core. Because of the matched core size, the PR demonstrates good compatibility with the established backbone networks which are composed of conventional SMFs. With optimized parameters for the auxiliary waveguide, the PR offers a near 100% polarization conversion efficiency at the 1550 nm band with a bandwidth of ∼30  nm, a length of ∼4625.9  μm with a large tolerance of ∼550  μm, and a tolerance of the input light polarization angle and rotation angle of the E7 LC of ∼π/30 and ∼π/36  rad, respectively. The performance was verified by the full-vector finite-element method. The proposed PR can be easily fabricated based on the existing photonics crystal fiber manufacturing process, making it a potentially inexpensive device for applications in modern communication systems. Moreover, the QOA, compared with the previous supermode-theory design method, allows a designer to consider several waveguides separately. Therefore, various unique characteristics can be met simultaneously which is consistent with the trend of modern fiber design.

A Profile of Defense Manufacturing Costs and Enabling Technologies

DTIC Science & Technology

1992-01-01

RECEIVE MODULE F Missiles 75mm Cadmium Zinc Telluride F 94 GHZ MILLIMETER WAVE TRANSCEIVER F COMPOSITES FOR PASSIVE THERMAL MANAGEMENT F COMPOSITES FOR... PASSIVE THERMAL MANAGEMENT F Design standards for surface mount devices I Electro-optic Components Advanced Manufacturing PrDcess I FIBER OPTIC

Analysis of roadside safety devices for use on very high-speed roadways.

DOT National Transportation Integrated Search

2009-09-01

The Texas Department of Transportation (TxDOT) is embarking on a multi-decade effort to expand : the states transportation system. TxDOT has expressed an interest in using very high design speeds (above : 80 mph) for some of these facilities to pr...

Coexistence of non-volatile bi-polar resistive switching and tunneling magnetoresistance in spatially confined La0.3Pr0.4Ca0.3MnO3 films

NASA Astrophysics Data System (ADS)

Jeon, J.; Jung, J.; Chow, K. H.

2017-12-01

We report the coexistence of non-volatile bi-polar resistive switching (RS) and tunneling magnetoresistance (TMR) in spatially confined La0.3Pr0.4Ca0.3MnO3 films grown on LaAlO3 substrates. At certain temperatures, the arrangement of electronic phase domains in these narrow systems mimics those found in heterostructured metal-insulator-metal devices. The relative spin orientations between adjacent ferromagnetic metallic phase domains enable the TMR effect, while the creation/annihilation of conduction filaments between the metallic phase domains produces the RS effect.

Green proteorhodopsin reconstituted into nanoscale phospholipid bilayers (nanodiscs) as photoactive monomers.

PubMed

Ranaghan, Matthew J; Schwall, Christine T; Alder, Nathan N; Birge, Robert R

2011-11-16

Over 4000 putative proteorhodopsins (PRs) have been identified throughout the oceans and seas of the Earth. The first of these eubacterial rhodopsins was discovered in 2000 and has expanded the family of microbial proton pumps to all three domains of life. With photophysical properties similar to those of bacteriorhodopsin, an archaeal proton pump, PRs are also generating interest for their potential use in various photonic applications. We perform here the first reconstitution of the minimal photoactive PR structure into nanoscale phospholipid bilayers (nanodiscs) to better understand how protein-protein and protein-lipid interactions influence the photophysical properties of PR. Spectral (steady-state and time-resolved UV-visible spectroscopy) and physical (size-exclusion chromatography and electron microscopy) characterization of these complexes confirms the preparation of a photoactive PR monomer within nanodiscs. Specifically, when embedded within a nanodisc, monomeric PR exhibits a titratable pK(a) (6.5-7.1) and photocycle lifetime (∼100-200 ms) that are comparable to the detergent-solubilized protein. These ndPRs also produce a photoactive blue-shifted absorbance, centered at 377 or 416 nm, that indicates that protein-protein interactions from a PR oligomer are required for a fast photocycle. Moreover, we demonstrate how these model membrane systems allow modulation of the PR photocycle by variation of the discoidal diameter (i.e., 10 or 12 nm), bilayer thickness (i.e., 23 or 26.5 Å), and degree of saturation of the lipid acyl chain. Nanodiscs also offer a highly stable environment of relevance to potential device applications.

Assistive Technology Needs and Measurement of the Psychosocial Impact of Assistive Technologies for Independent Living of Older Hispanics: Lessons Learned

PubMed Central

Orellano-Colón, Elsa M.; Jutai, Jeffrey; Santiago, Angélica; Torres, Víctor; Benítez, Keyla; Torres, Mayra

2016-01-01

(1) Knowledge about the assistive technology (AT) needs and psychosocial impact of AT in different populations is needed because the adoption, retention, or abandonment of AT may be influenced by the psychosocial impact that AT has on its users. The aims of this study were to: (a) identify the AT needs of a sample of Hispanic older adults with functional limitations, (b) describe the psychosocial impact of these technologies on the sample’s quality of life, and (c) describe the methodological challenges in using the Puerto Rican version of the Psychosocial Impact of Assistive Device Scale (PR-PIADS) with a Hispanic sample. (2) Methods: This study used a cross-sectional design conducted with a sample of 60 participants. Data was collected using the Assistive Technology Card Assessment Questionnaire (ATCAQ) and the PR-PIADS. Data analyses included descriptive statistics and bivariate analysis. (3) Results: The sample’s most frequently reported needs for AT devices were in the areas of cooking, home tasks, and home safety activities. The sample reported a positive impact of AT use in their quality of life. Several methodological challenges of the PIADS were identified. (4) Conclusions: The sample has unmet needs for using AT devices to overcome difficulties in daily living activities. PMID:27695688

Assistive Technology Needs and Measurement of the Psychosocial Impact of Assistive Technologies for Independent Living of Older Hispanics: Lessons Learned.

PubMed

Orellano-Colón, Elsa M; Jutai, Jeffrey; Santiago, Angélica; Torres, Víctor; Benítez, Keyla; Torres, Mayra

2016-09-01

(1) Knowledge about the assistive technology (AT) needs and psychosocial impact of AT in different populations is needed because the adoption, retention, or abandonment of AT may be influenced by the psychosocial impact that AT has on its users. The aims of this study were to: (a) identify the AT needs of a sample of Hispanic older adults with functional limitations, (b) describe the psychosocial impact of these technologies on the sample's quality of life, and (c) describe the methodological challenges in using the Puerto Rican version of the Psychosocial Impact of Assistive Device Scale (PR-PIADS) with a Hispanic sample. (2) Methods: This study used a cross-sectional design conducted with a sample of 60 participants. Data was collected using the Assistive Technology Card Assessment Questionnaire (ATCAQ) and the PR-PIADS. Data analyses included descriptive statistics and bivariate analysis. (3) Results: The sample's most frequently reported needs for AT devices were in the areas of cooking, home tasks, and home safety activities. The sample reported a positive impact of AT use in their quality of life. Several methodological challenges of the PIADS were identified. (4) Conclusions: The sample has unmet needs for using AT devices to overcome difficulties in daily living activities.

MouthLab: A Tricorder Concept Optimized for Rapid Medical Assessment.

PubMed

Fridman, Gene Y; Tang, Hai; Feller-Kopman, David; Hong, Yang

2015-09-01

The goal of rapid medical assessment (RMA) is to estimate the general health of a patient during an emergency room or a doctor's office visit, or even while the patient is at home. Currently the devices used during RMA are typically "all-in-one" vital signs monitors. They require time, effort and expertise to attach various sensors to the body. A device optimized for RMA should instead require little effort or expertise to operate and be able to rapidly obtain and consolidate as much information as possible. MouthLab is a battery powered hand-held device intended to acquire and evaluate many measurements such as non-invasive blood sugar, saliva and respiratory biochemistry. Our initial prototype acquires standard vital signs: pulse rate (PR), breathing rate (BR), temperature (T), blood oxygen saturation (SpO2), blood pressure (BP), and a three-lead electrocardiogram. In our clinical study we tested the device performance against the measurements obtained with a standard patient monitor. 52 people participated in the study. The measurement errors were as follows: PR: -1.7 ± 3.5 BPM, BR: 0.4 ± 2.4 BPM, T: -0.4 ± 1.24 °F, SpO2: -0.6 ± 1.7%. BP systolic: -1.8 ± 12 mmHg, BP diastolic: 0.6 ± 8 mmHg. We have shown that RMA can be easily performed non-invasively by patients with no prior training.

The selection of air traffic control specialists : two studies demonstrating methods to insure an accurate validity coefficient for selection devices.

DOT National Transportation Integrated Search

1979-03-01

There are several conditions that can influence the calculation of the statistical validity of a test battery such as that used to selected Air Traffic Control Specialists. Two conditions of prime importance to statistical validity are recruitment pr...

78 FR 18233 - Medical Devices; Technical Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... the right column: Section Remove Add 814.20 http://www.fda.gov/ http://www.fda.gov/ cdrh/devadvice.../ PremarketApproval PMA/default.htm. 822.7 http://www.fda.gov/ http://www.fda.gov/ cdrh/ombudsman/ AboutFDA/ dispute.html. CentersOffices/ OfficeofMedicalPr oductsandTobacco/ CDRH/ CDRHOmbudsman/ default.htm. 822.15...

Some people move it, move it… for pressure injury prevention.

PubMed

Sonenblum, Sharon E; Sprigle, Stephen H

2018-01-01

To describe differences in in-seat behavior observed between individuals with a spinal cord injury (SCI) with and without a history of recurrent pressure injuries. Cross-sectional cohort study. General community. Twenty-nine adults more than 2 years post SCI, who used a wheelchair as their primary mobility device and had the ability to independently perform weight shift maneuvers. Participants were grouped according to whether or not they had a history of recurrent pressure injuries (PrIs), with 12 subjects having had two or more pressure injuries in the pelvic area (PrI Group). Not applicable. Daily time in wheelchair, number of transfers, and frequency of pressure reliefs (full unloading), weight shifts (30% load reduction), and in-seat movements (transient center of pressure movements or unloading). The median participant spent 10.3 hours in his wheelchair and performed 16 transfers to or from the wheelchair daily. Pressure reliefs were performed less than once every 3 hours in both groups. Weight shifts were performed significantly more often by the No PrI Group (median (interquartile range) 2.5 (1.0-3.6) per hour) than the PrI Group (1.0 (0.4-1.9), with P = 0.037 and effect size r = 0.39). In-seat movements were performed 46.5 (28.7-76.7) times per hour by the No PrI group and 39.6 (24.3-49.7) times per hour for the PrI group (P = 0.352, effect size r = 0.17). Weight shifts that can be produced by functional activities and that partially unload the buttocks should be considered as an important addition to individuals' PrI prevention regimen.

Resistive switching mechanisms in random access memory devices incorporating transition metal oxides: TiO2, NiO and Pr0.7Ca0.3MnO3.

PubMed

Magyari-Köpe, Blanka; Tendulkar, Mihir; Park, Seong-Geon; Lee, Hyung Dong; Nishi, Yoshio

2011-06-24

Resistance change random access memory (RRAM) cells, typically built as MIM capacitor structures, consist of insulating layers I sandwiched between metal layers M, where the insulator performs the resistance switching operation. These devices can be electrically switched between two or more stable resistance states at a speed of nanoseconds, with long retention times, high switching endurance, low read voltage, and large switching windows. They are attractive candidates for next-generation non-volatile memory, particularly as a flash successor, as the material properties can be scaled to the nanometer regime. Several resistance switching models have been suggested so far for transition metal oxide based devices, such as charge trapping, conductive filament formation, Schottky barrier modulation, and electrochemical migration of point defects. The underlying fundamental principles of the switching mechanism still lack a detailed understanding, i.e. how to control and modulate the electrical characteristics of devices incorporating defects and impurities, such as oxygen vacancies, metal interstitials, hydrogen, and other metallic atoms acting as dopants. In this paper, state of the art ab initio theoretical methods are employed to understand the effects that filamentary types of stable oxygen vacancy configurations in TiO(2) and NiO have on the electronic conduction. It is shown that strong electronic interactions between metal ions adjacent to oxygen vacancy sites results in the formation of a conductive path and thus can explain the 'ON' site conduction in these materials. Implication of hydrogen doping on electroforming is discussed for Pr(0.7)Ca(0.3)MnO(3) devices based on electrical characterization and FTIR measurements.

Long-Term Outcome and Predictors of Noninstitutionalized Survival Subsequent to Prolonged Intensive Care Unit Stay After Cardiac Surgical Procedures.

PubMed

Manji, Rizwan A; Arora, Rakesh C; Singal, Rohit K; Hiebert, Brett; Moon, Michael C; Freed, Darren H; Menkis, Alan H

2016-01-01

There are minimal data on long-term functional survival (alive and not institutionalized) in patients undergoing cardiac operations who require a prolonged intensive care unit length of stay (prICULOS). We sought to describe 1- and 5-year functional survival in patients who had a prICULOS (ICULOS ≥ 5 days) and determine predictors of functional survival at 1 year. Data were obtained from linked clinical and administrative databases from January 1, 2000 to December 31, 2011 to conduct this retrospective single-region analysis. Logistic regression was used to develop a model predicting functional survival at 1 year for patients who had a prICULOS after cardiac operations. There were 9,545 admissions to the ICU after cardiac operations; of these patients, 728 (7.6%) experienced a prICULOS. There was an increasing trend in patients who had a prICULOS over this study period. The functional survival at 1 and 5 years from the surgical procedure for the non-prICULOS versus the prICULOS cohort was 1 year (94.9% versus 73.9%) and 5 years (84.9% versus 53.8%) (p < 0.001). Factors associated with lower rates of functional survival at 1 year were age 80 years or older, female sex, peripheral vascular disease, preoperative renal dysfunction, cerebrovascular disease, preoperative infection, need for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) after cardiotomy, number of days on mechanical ventilation, and number of days in the ICU beyond 5 days (area under the receiver operating characteristic [ROC] curve = 0.766). The majority of patients who had a prICULOS experienced successful functional survival up to 5 years after cardiac operations. Identification of risk factors for poor functional survival may be of assistance to clinicians, patients, and families for prognostication and decision making. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Four-state non-volatile memory in a multiferroic spin filter tunnel junction

NASA Astrophysics Data System (ADS)

Ruan, Jieji; Li, Chen; Yuan, Zhoushen; Wang, Peng; Li, Aidong; Wu, Di

2016-12-01

We report a spin filter type multiferroic tunnel junction with a ferromagnetic/ferroelectric bilayer barrier. Memory functions of a spin filter magnetic tunnel junction and a ferroelectric tunnel junction are combined in this single device, producing four non-volatile resistive states that can be read out in a non-destructive manner. This concept is demonstrated in a LaNiO3/Pr0.8Ca0.2MnO3/BaTiO3/La0.7Sr0.3MnO3 all-oxide tunnel junction. The ferromagnetic insulator Pr0.8Ca0.2MnO3 serves as the spin filter and the ferromagnetic metal La0.7Sr0.3MnO3 is the spin analyzer. The ferroelectric polarization reversal in the BaTiO3 barrier switches the tunneling barrier height to produce a tunneling electroresistance. The ferroelectric switching also modulates the spin polarization and the spin filtering efficiency in Pr0.8Ca0.2MnO3.

Toward pressure-induced multiferroicity in PrMn2O5

NASA Astrophysics Data System (ADS)

Peng, W.; Balédent, V.; Chattopadhyay, S.; Lepetit, M.-B.; Yahia, G.; Colin, C. V.; Gooch, M. J.; Pasquier, C. R.; Auban-Senzier, P.; Greenblatt, M.; Foury-Leylekian, P.

2017-08-01

The series of multiferroics R Mn2O5 is extensively studied for its quasicollinear spin arrangement, which results in an electrical polarization according to the exchange-striction model. Variations of the interatomic distances modified by the external pressure can strongly influence the multiferroic properties. Understanding this influence is of great importance, especially for the future realization of multiferroic devices. As PrMn2O5 is paraelectric at ambient pressure, it is the most suitable candidate to search for pressure induced multiferroicity. In this paper, we report the emergence of a new pressure induced magnetic phase in PrMn2O5 determined by powder neutron diffraction under pressure. This new magnetic phase presenting at relatively low pressure becomes completely exclusive at 8 GPa. The determination of its magnetic structure has thus been possible for the first time. More importantly, the magnetic structure stabilized under pressure should induce a strong spontaneous electric polarization due to the nearly perfect collinearity of the Mn3 + and Mn4 + spins.

Effects of Er3+ and Pr3+ Substitution on Structural, Dielectric, Ferroelectric and Photoluminescence Properties of the BaTi0.9Zr0.1O3 Ceramic

NASA Astrophysics Data System (ADS)

Zouari, I.; Sassi, Z.; Seveyrat, L.; Perrin, V.; Zghal, S.; Abdelmoula, N.; Lebrun, L.; Khemakhem, H.

2017-07-01

BaTi0.9Zr0.1O3 (BZT), Ba1- x Ln2 x/3□ x/3Ti0.9Zr0.1O3 (with x = 0.5% mol and Ln = Er3+) (BZT-Er) and Ba1- x Ln2 x/3□ x/3Ti0.9Zr0.1O3 (with x = 0.5% mol and Ln = Pr3+) (BZT-Pr) were prepared via the conventional solid-state reaction method. X-ray diffraction showed that all these ceramics were in the single perovskite phase at room temperature (RT). The temperature dependence of dielectric behavior was investigated in the temperature range 25-225°C and exhibited a classical ferroelectric behavior. A slight decrease of the Curie temperature ( T C) with Pr3+ and Er3+ substitution was observed in addition to an increase in the maximum dielectric permittivity ( \\varepsilon_{r {max} }^' }} ) of about 40% for the BZT-Er. At RT, the ferroelectric and piezoelectric coefficients were decreased for BZT-Pr, but were maintained for BZT-Er with a piezoelectric coefficient ( d 33) of 185 pC/N, a planar electromechanical coupling factor of 30%, and a remanent polarization of 11.6 μC/cm2. The Raman bands as a function of temperature confirmed the paraelectric-ferroelectric phase transition of all those ceramics. The photoluminescence spectra showed that strong red (615 nm and 645 nm) and bright green (523 nm and 545 nm) emission bands were obtained, under excitation by laser at 488 nm at RT, for BZT-Pr and BZT-Er, respectively. These multifunctional materials showed a significant technological promise in coupling device applications.

Sexually Transmitted Infection Prevention With Long-Acting Reversible Contraception: Factors Associated With Dual Use.

PubMed

Thompson, Erika L; Vamos, Cheryl A; Griner, Stacey B; Logan, Rachel; Vázquez-Otero, Coralia; Daley, Ellen M

2017-07-01

Long-acting reversible contraception (LARC) is extremely effective in preventing pregnancy; however, it does not provide sexually transmitted infection (STI) prevention. Therefore, dual use is recommended for the prevention of STIs, in addition to pregnancy, by using LARC methods with condoms. This study assessed factors associated with LARC only use and dual-LARC and condom use among college women. The National College Health Assessment-II Fall 2012 to 2013 was used for this analysis. The analytic sample was restricted to women who used a LARC method (ie, intrauterine device or implant) (N = 1658). The main outcome was dual method use, LARC and condom, at last sex. An adjusted logistic regression model assessed sociodemographic factors (age, relationship, race), health care utilization (routine gynecological examination), and sexual behavior (number of partners) as factors associated with dual condom-LARC use at the last time of vaginal-sex. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated. Among women reporting LARC use, 24% used a condom. Dual users were less likely to have only 1 sexual partner (adjusted PR [aPR], 0.66; 95% CI, 0.54-0.81) and be in a relationship. Dual users were more likely than LARC-only users to be Hispanic (aPR, 1.34; 95% CI, 1.01-1.78), black (aPR, 1.40; 95% CI, 1.07-1.83), and biracial/multiracial (aPR, 1.38; 95% CI, 1.10-1.73). These findings illustrate differences between dual-condom LARC and LARC-only college users. It is likely that relationship status and number of partners influences perceived risk for STIs and decision making for dual use among this population.

Effect of an office ergonomic randomised controlled trial among workers with neck and upper extremity pain.

PubMed

Dropkin, Jonathan; Kim, Hyun; Punnett, Laura; Wegman, David H; Warren, Nicholas; Buchholz, Bryan

2015-01-01

Office computer workers are at increased risk for neck/upper extremity (UE) musculoskeletal pain. A seven-month office ergonomic intervention study evaluated the effect of two engineering controls plus training on neck/UE pain and mechanical exposures in 113 computer workers, including a 3-month follow-up period. Participants were randomised into an intervention group, who received a keyboard/mouse tray (KBT), touch pad (TP) for the non-dominant hand and keyboard shortcuts, and a control group who received keyboard shortcuts. Participants continued to have available a mouse at the dominant hand. Outcomes were pain severity, computer rapid upper limb assessment (RULA), and hand activity level. Prevalence ratios (PRs) evaluated intervention effects using dichotomised pain and exposure scores. In the intervention group, the dominnt proximal UE pain PR=0.9, 95% CI 0.7 to 1.2 and the dominant distal UE PR=0.8, 95% CI 0.5 to 1.3, postintervention. The non-dominant proximal UE pain PR=1.0, 95% CI 0.8 to 1.4, while the non-dominant distal UE PR=1.2, 95% CI 0.6 to 2.2, postintervention. Decreases in non-neutral postures were found in two RULA elements (non-dominant UE PR=0.9, 95% CI 0.8 to 0.9 and full non-dominant RULA PR=0.8, 95% CI 0.8 to 0.9) of the intervention group. Hand activity increased on the non-dominant side (PR=1.4, 95% CI 1.2 to 1.6) in this group. While the intervention reduced non-neutral postures in the non-dominant UE, it increased hand activity in the distal region of this extremity. To achieve lower hand activity, a KBT and TP used in the non-dominant hand may not be the best devices to use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Periodically structured Si pillars for high-performing heterojunction photodetectors

NASA Astrophysics Data System (ADS)

Melvin David Kumar, M.; Yun, Ju-Hyung; Kim, Joondong

2015-03-01

A periodical array of silicon (Si) micro pillar structures was fabricated on Si substrates using PR etching process. Indium tin oxide (ITO) layer of 80 nm thickness was deposited over patterned Si substrates so as to make ITO/n-Si heterojunction devices. The influences of width and period of pillars on the optical and electrical properties of prepared devices were investigated. The surface morphology of the Si substrates revealed the uniform array of pillar structures. The 5/10 (width/period) Si pillar pattern reduced the optical reflectance to 6.5% from 17% which is of 5/7 pillar pattern. The current rectifying ratio was found higher for the device in which the pillars are situated in optimum periods. At both visible (600 nm) and near infrared (900 nm) range of wavelengths, the 5/7 and 5/10 pillar patterned device exhibited the better photoresponses which are suitable for making advanced photodetectors. This highly transmittance and photoresponsive pillar patterned Si substrates with an ITO layer would be a promising device for various photoelectric applications.

A novel Online-to-Offline (O2O) model for pre-exposure prophylaxis and HIV testing scale up.

PubMed

Anand, Tarandeep; Nitpolprasert, Chattiya; Trachunthong, Deondara; Kerr, Stephen J; Janyam, Surang; Linjongrat, Danai; Hightow-Weidman, Lisa B; Phanuphak, Praphan; Ananworanich, Jintanat; Phanuphak, Nittaya

2017-03-13

PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online-to-Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. The O2O model was piloted by Adam's Love (www.adamslove.org) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam's Love online staff, received real-time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto-generated site- and service-specific e-tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check-in by offline site staff. Service uptake and participant's socio-demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Between January 10th and April 11th, 2016, Adam's Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e-tickets. There were 325 (76.5%) MSM and TG who checked-in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e-ticket and checking-in was 3 (0-7) days. Of 316 HIV-negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14-4.66; p  = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19-3.54; p  = 0.009), being aware of sexual partners' HIV status (OR 2.37, 95%CI 1.29-4.35; p  = 0.008), ever previously using post-exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19-5.09; p  = 0.01), and enrolment at Adam's Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06-6.95; p  < 0.001) were independently associated with PrEP uptake. Adam's Love O2O model is highly effective in linking online at-risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations.

Simulating Photo-Refraction Images of Keratoconus and Near-Sightedness Eyes

NASA Astrophysics Data System (ADS)

Baker, Kevin; Lewis, James W. L.; Chen, Ying-Ling

2004-11-01

Keratoconus is an abnormal condition of the eye resulting from cone-shaped features on the cornea that degrade the quality of vision. These corneal features result from thinning and subsequent bulging due to intraocular pressure. The abnormal corneal curvature increases the refractive power asymmetrically and can be misdiagnosed by examiners as astigmatism and nearsightedness. Since corrective treatment is possible, early detection of this condition is desirable. Photo-refraction (PR) detects the retinal irradiance reflected from a single light source and is an inexpensive method used to identify refractive errors. For near- (far-) sighted eye, a crescent appears on the same (opposite) side of the light source. The capability of a PR device to detect keratoconus and to differentiate this condition from myopia was investigated. Using a commercial optical program, synthetic eye models were constructed for both near-sighted and keratoconus eyes. PR images of various eye conditions were calculated. The keratoconus cone shapes were modeled with typical published cone locations and sizes. The results indicate significant differences between the images of keratoconus and near-sighted eyes.

Comparison of two scanning instruments to measure peripheral refraction in the human eye.

PubMed

Jaeken, Bart; Tabernero, Juan; Schaeffel, Frank; Artal, Pablo

2012-03-01

To better understand how peripheral refraction affects development of myopia in humans, specialized instruments are fundamental for precise and rapid measurements of refraction over the visual field. We compare here two prototype instruments that measure in a few seconds the peripheral refraction in the eye with high angular resolution over a range of about ±45 deg. One instrument is based on the continuous recording of Hartmann-Shack (HS) images (HS scanner) and the other is based on the photorefraction (PR) principle (PR scanner). On average, good correlations were found between the refraction results provided by the two devices, although it varied across subjects. A detailed statistical analysis of the differences between both instruments was performed based on measurements in 35 young subjects. Both instruments have advantages and disadvantages. The HS scanner also provides the high-order aberration data, while the PR scanner is more compact and has a lower cost. Both instruments are current prototypes, and further optimization is possible to make them even more suitable tools for future visual optics and myopia research and also for different ophthalmic applications.

Photorefractive splicing device with double phase conjugate mirror using Sn2P2S6:Sb crystal

NASA Astrophysics Data System (ADS)

Wakayama, Yuta; Okamoto, Atsushi; Shimayabu, Kohei; Kojima, Yasunori; Grabar, Alexander A.

2009-02-01

We develop a splicing device for photonic crystal fibers (PCFs) based on a double phase conjugate mirror (DPCM) using a novel photorefractive (PR) Sn2P2S6:Sb 1.5% crystal. This PR splicer has many attractive characteristics including modal field compensation and the automatic reconfiguration of the optical path. Utilizing a DPCM as the splicer, our device can adapt to misalignments automatically since the incident beams continuously rewrite an index grating which formed in the crystal. By the implementation of the Sn2P2S6:Sb crystal, the response time for the characteristic of dynamic reconfiguration is improved several-hundred-fold compared with conventional materials, e.g. BaTiO3. We demonstrate that the high angular tolerance is provided using the DPCM with the Sn2P2S6:Sb crystal. When the misalignment of the incident angle is from -7° to 8°, the increment of coupling loss is less than 0.6dB. This is several-ten-fold compared with the fusion splicing. We reveal the dependence of the coupling loss on the position of the incident beams and also the dependence of the energy flow on the propagation distance for the first time with the two-dimensional finite-difference beampropagation method. Using our numerical simulation tool, we can visually investigate the beam propagation property considering the influence of the fanning effect in the Sn2P2S6 crystals.

Development of novel nonvolatile memory devices using the colossal magnetoresistive oxide praseodymium-calcium-manganese trioxide

NASA Astrophysics Data System (ADS)

Papagianni, Christina

Pr0.7Ca0.3MnO3 (PCMO) manganese oxide belongs in the family of materials known as transition metal oxides. These compounds have received increased attention due to their perplexing properties such as Colossal Magnetoresistance effect, Charge-Ordered phase, existence of phase-separated states etc. In addition, it was recently discovered that short electrical pulses in amplitude and duration are sufficient to induce reversible and non-volatile resistance changes in manganese perovskite oxide thin films at room temperature, known as the EPIR effect. The existence of the EPIR effect in PCMO thin films at room temperature opens a viable way for the realization of fast, high-density, low power non-volatile memory devices in the near future. The purpose of this study is to investigate, optimize and understand the properties of Pr0.7Ca0.3MnO 3 (PCMO) thin film devices and to identify how these properties affect the EPIR effect. PCMO thin films were deposited on various substrates, such as metals, and conducting and insulating oxides, by pulsed laser and radio frequency sputtering methods. Our objective was to understand and compare the induced resistive states. We attempted to identify the induced resistance changes by considering two resistive models to be equivalent to our devices. Impedance spectroscopy was also utilized in a wide temperature range that was extended down to 70K. Fitted results of the temperature dependence of the resistance states were also included in this study. In the same temperature range, we probed the resistance changes in PCMO thin films and we examined whether the phase transitions affect the EPIR effect. In addition, we included a comparison of devices with electrodes consisting of different size and different materials. We demonstrated a direct relation between the EPIR effect and the phase diagram of bulk PCMO samples. A model that could account for the observed EPIR effect is presented.

[Gastric mucosa tonometry in routine monitoring in the surgical intensive care unit].

PubMed

Pestel, G; Uhlig, T; Götschl, A; Schmucker, P; Rothhammer, A

1998-06-01

Monitoring tissue oxygenation in the splanchnic region could be helpful for critically ill patients. In this study the postoperative course of gastric mucosal CO2 (prCO2) in 40 patients is shown. Following approval of the ethics committee, 24 patients schedulded for surgery with an expected large fluid turnover and 16 multiple injured patients were monitored with a gas tonometry device in addition to standard monitoring (ECG, pulse oximetry, capnometry, CVP, arterial pressure). Normoventilated patients with prCO2 > 50 for more than 30 minutes were treated with fluid therapy, followed by catecholamine therapy, followed by transfusion (fig. 1). All patients were admitted to the SICU post-operatively. The variation of prCO2-values was greater in multiple injured patients. Their prCO2-values began in a lower range compared to patients with scheduled operation, became higher at the end of the first SICU-day and remained higher thereafter. They had a higher fluid turnover and needed more catecholamines. Multiple injured patients with an arterio-intestinal CO2-Difference (CO2-Gap) > 10 had a higher ISS-Score, were longer mechanically ventilated, had a longer SICU-stay and a higher incidence of complications in comparison to patients with aCO2-Gap < 10. Perhaps a CO2-Gap > 10 could be predictive for a more severe course in intensive care patients.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, P; Cammin, J; Solberg, T

Purpose: Proton radiography and proton computed tomography (PCT) can be used to measure proton stopping power directly. However, practical and cost effective proton imaging detectors are not widely available. In this study, the authors investigated the feasibility of proton imaging using a silicon diode array. Methods: A one-dimensional silicon-diode detector array (1DSDA) was aligned with the central axis (CAX) of the proton beam. Polymethyl methacrylate (PMMA) slabs were used to find the correspondence between the water equivalent thickness (WET) and 1DSDA channel number. 2D proton radiographs (PR) were obtained by translation and rotation of a phantom relative to CAX whilemore » the proton nozzle and 1DSDA were kept stationary. A PCT image of one slice of the phantom was reconstructed using filtered backprojection. Results: PR and PCT images of the PMMA cube were successfully acquired using the 1DSDA. The WET of the phantom was measured using PR data with an accuracy of 4.2% or better. Structures down to 1 mm in size could be resolved. Reconstruction of a PCT image showed very good agreement with simulation. Limitations in spatial resolution are attributed to limited spatial sampling, beam collimation, and proton scatter. Conclusion: The results demonstrate the feasibility of using silicon diode arrays for proton imaging. Such a device can potentially offer fast image acquisition, high spatial and energy resolution for PR and PCT.« less

Performance Evaluation of New-Generation Pulse Oximeters in the NICU: Observational Study.

PubMed

Nizami, Shermeen; Greenwood, Kim; Barrowman, Nick; Harrold, JoAnn

2015-09-01

This crossover observational study compares the data characteristics and performance of new-generation Nellcor OXIMAX and Masimo SET SmartPod pulse oximeter technologies. The study was conducted independent of either original equipment manufacturer (OEM) across eleven preterm infants in a Neonatal Intensive Care Unit (NICU). The SmartPods were integrated with Dräger Infinity Delta monitors. The Delta monitor measured the heart rate (HR) using an independent electrocardiogram sensor, and the two SmartPods collected arterial oxygen saturation (SpO2) and pulse rate (PR). All patient data were non-Gaussian. Nellcor PR showed a higher correlation with the HR as compared to Masimo PR. The statistically significant difference found in their median values (1% for SpO2, 1 bpm for PR) was deemed clinically insignificant. SpO2 alarms generated by both SmartPods were observed and categorized for performance evaluation. Results for sensitivity, positive predictive value, accuracy and false alarm rates were Nellcor (80.3, 50, 44.5, 50%) and Masimo (72.2, 48.2, 40.6, 51.8%) respectively. These metrics were not statistically significantly different between the two pulse oximeters. Despite claims by OEMs, both pulse oximeters exhibited high false alarm rates, with no statistically or clinically significant difference in performance. These findings have a direct impact on alarm fatigue in the NICU. Performance evaluation studies can also impact medical device purchase decisions made by hospital administrators.

Enzymatic Formulation Capable of Degrading Scrapie Prion under Mild Digestion Conditions

PubMed Central

Okoroma, Emeka A.; Purchase, Diane; Garelick, Hemda; Morris, Roger; Neale, Michael H.; Windl, Otto; Abiola, Oduola O.

2013-01-01

The prion agent is notoriously resistant to common proteases and conventional sterilisation procedures. The current methods known to destroy prion infectivity such as incineration, alkaline and thermal hydrolysis are harsh, destructive, environmentally polluting and potentially hazardous, thus limit their applications for decontamination of delicate medical and laboratory devices, remediation of prion contaminated environment and for processing animal by-products including specified risk materials and carcases. Therefore, an environmentally friendly, non-destructive enzymatic degradation approach is highly desirable. A feather-degrading Bacillus licheniformis N22 keratinase has been isolated which degraded scrapie prion to undetectable level of PrPSc signals as determined by Western Blot analysis. Prion infectivity was verified by ex vivo cell-based assay. An enzymatic formulation combining N22 keratinase and biosurfactant derived from Pseudomonas aeruginosa degraded PrPSc at 65°C in 10 min to undetectable level -. A time-course degradation analysis carried out at 50°C over 2 h revealed the progressive attenuation of PrPSc intensity. Test of residual infectivity by standard cell culture assay confirmed that the enzymatic formulation reduced PrPSc infectivity to undetectable levels as compared to cells challenged with untreated standard scrapie sheep prion (SSBP/1) (p-value = 0.008 at 95% confidence interval). This novel enzymatic formulation has significant potential application for prion decontamination in various environmentally friendly systems under mild treatment conditions. PMID:23874511

Stenotrophomonas maltophilia isolated from patients exposed to invasive devices in a university hospital in Argentina: molecular typing, susceptibility and detection of potential virulence factors.

PubMed

Alcaraz, Eliana; Garcia, Carlos; Papalia, Mariana; Vay, Carlos; Friedman, Laura; Passerini de Rossi, Beatriz

2018-05-25

The aim of this work was to investigate the presence of selected potential virulence factors, susceptibility and clonal relatedness among 63 Stenotrophomonas maltophilia isolates recovered from patients exposed to invasive devices in a university hospital in Argentina between January 2004 and August 2012. Genetic relatedness was assessed by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and pulsed-field gel electrophoresis (PFGE). Isolates were characterized by antimicrobial resistance, the presence and/or expression of potential virulence determinants, and virulence in the Galleria mellonella model.Results/Key findings. ERIC-PCR generated 52 fingerprints, and PFGE added another pattern. Resistance to trimethoprim-sulfamethoxazole (6.35 %), levofloxacin (9.52 %) and ciprofloxacin (23.80 %) was detected. All isolates were susceptible to minocycline. All isolates were lipase, protease and siderophore producers, while all but Sm61 formed biofilms. However, 11/63 isolates did not amplify the major extracellular protease-coding gene (stmPr1). Sm61 is an stmPr1-negative isolate, and showed (as did Sm13 and the reference strain K279a) strong proteolysis and siderophore production, and high resistance to hydrogen peroxide. The three isolates were virulent in the G. mellonella model, while Sm10, a low-resistance hydrogen peroxide stmPr1-negative isolate, and weak proteolysis and siderophore producer, was not virulent. This is the first epidemiological study of the clonal relatedness of S. maltophilia clinical isolates in Argentina. Great genomic diversity was observed, and only two small clusters of related S. maltophilia types were found. Minocycline and trimethoprim-sulfamethoxazole were the most active agents. S. maltophilia virulence in the G. mellonella model is multifactorial, and further studies are needed to elucidate the role of each potential virulence factor.

Assessment of Phospohrene Field Effect Transistors

DTIC Science & Technology

2018-01-28

electronics industry. To this end, transistor test structures would initially be fabricated on phosphorene exfoliated from black phosphorus and, later, on...34Phosphorene FETs-Promising Transistors Based on a few Layers of Phosphorus Atoms," Nanjing Electronic Devices Institute, Nanjing, China, Jul. 2015...OH, Nov. 2015. J.C. M. Hwang, "Phosphorene Transistors-Transient or Lasting Electronics ?" Workshop Frontier Electronics , San Juan, PR, Dec. 2015

A novel Online-to-Offline (O2O) model for pre-exposure prophylaxis and HIV testing scale up

PubMed Central

Anand, Tarandeep; Nitpolprasert, Chattiya; Trachunthong, Deondara; Kerr, Stephen J; Janyam, Surang; Linjongrat, Danai; Hightow-Weidman, Lisa B; Phanuphak, Praphan; Ananworanich, Jintanat; Phanuphak, Nittaya

2017-01-01

Abstract Introduction: PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam’s Love Online-to-Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. Methods: The O2O model was piloted by Adam’s Love (www.adamslove.org) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam’s Love online staff, received real-time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto-generated site- and service-specific e-tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check-in by offline site staff. Service uptake and participant’s socio-demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Results: Between January 10th and April 11th, 2016, Adam’s Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e-tickets. There were 325 (76.5%) MSM and TG who checked-in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e-ticket and checking-in was 3 (0–7) days. Of 316 HIV-negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14–4.66; p = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19–3.54; p = 0.009), being aware of sexual partners’ HIV status (OR 2.37, 95%CI 1.29–4.35; p = 0.008), ever previously using post-exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19–5.09; p = 0.01), and enrolment at Adam’s Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06–6.95; p < 0.001) were independently associated with PrEP uptake. Conclusions: Adam’s Love O2O model is highly effective in linking online at-risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations. PMID:28362062

Little Brother Joins the Large Family

NASA Astrophysics Data System (ADS)

2006-12-01

On the night of 15 December 2006, the fourth and last-to-be-installed VLTI Auxiliary Telescope (AT4) obtained its 'First Light'. The first images demonstrate that AT4 will be able to deliver the excellent image quality already delivered by the first three ATs. It will soon join its siblings to perform routinely interferometric measurements. ESO PR Photo 51a/06 ESO PR Photo 51a/06 VLT Auxiliary Telescope The VLT is composed of four 8.2-m Unit Telescope (Antu, Kueyen, Melipal and Yepun). They have been progressively put into service together with a vast suite of the most advanced astronomical instruments and are operated every night in the year. Contrary to other large astronomical telescopes, the VLT was designed from the beginning with the use of interferometry as a major goal. The VLT Interferometer (VLTI) combines starlight captured by two or three 8.2- VLT Unit Telescopes, dramatically increasing the spatial resolution and showing fine details of a large variety of celestial objects. ESO PR Photo 51b/06 ESO PR Photo 51b/06 One AT Under the Sky However, most of the time the large telescopes are used for other research purposes. They are therefore only available for interferometric observations during a limited number of nights every year. Thus, in order to exploit the VLTI each night and to achieve the full potential of this unique setup, some other (smaller), dedicated telescopes were included into the overall VLT concept. These telescopes, known as the VLTI Auxiliary Telescopes (ATs), are mounted on tracks and can be placed at precisely defined "parking" observing positions on the observatory platform. From these positions, their light beams are fed into the same common focal point via a complex system of reflecting mirrors mounted in an underground system of tunnels. The Auxiliary Telescopes are real technological jewels. They are placed in ultra-compact enclosures, complete with all necessary electronics, an air conditioning system and cooling liquid for thermal control, compressed air for enclosure seals, a hydraulic plant for opening the dome shells, etc. Each AT is also fitted with a transporter that lifts the telescope and relocates it from one station to another. It moves around with its own housing on the top of Paranal, almost like a snail. The VLTI is arguably the world's most advanced optical device of this type. It has already demonstrated its powerful capabilities by addressing several key scientific issues, such as determining the size and the shape of a variety of stars (ESO PR 22/02, PR 14/03, PR 31/03, and PR 09/06), measuring distances to stars (ESO PR 25/04), probing the innermost regions of the proto-planetary discs around young stars (ESO PR 27/04 and PR 35/06) or making the first detection by infrared interferometry of an extragalactic object (ESO PR 17/03).

A DICOM-RT radiation oncology ePR with decision support utilizing a quantified knowledge base from historical data

NASA Astrophysics Data System (ADS)

Documet, Jorge R.; Liu, Brent; Le, Anh; Law, Maria

2008-03-01

During the last 2 years we have been working on developing a DICOM-RT (Radiation Therapy) ePR (Electronic Patient Record) with decision support that will allow physicists and radiation oncologists during their decision-making process. This ePR allows offline treatment dose calculations and plan evaluation, while at the same time it compares and quantifies treatment planning algorithms using DICOM-RT objects. The ePR framework permits the addition of visualization, processing, and analysis tools, which combined with the core functionality of reporting, importing and exporting of medical studies, creates a very powerful application that can improve the efficiency while planning cancer treatments. Usually a Radiation Oncology department will have disparate and complex data generated by the RT modalities as well as data scattered in RT Information/Management systems, Record & Verify systems, and Treatment Planning Systems (TPS) which can compromise the efficiency of the clinical workflow since the data crucial for a clinical decision may be time-consuming to retrieve, temporarily missing, or even lost. To address these shortcomings, the ACR-NEMA Standards Committee extended its DICOM (Digital Imaging & Communications in Medicine) standard from Radiology to RT by ratifying seven DICOM RT objects starting in 1997 [1,2]. However, they are not broadly used yet by the RT community in daily clinical operations. In the past, the research focus of an RT department has primarily been developing new protocols and devices to improve treatment process and outcomes of cancer patients with minimal effort dedicated to integration of imaging and information systems. Our attempt is to show a proof-of-concept that a DICOM-RT ePR system can be developed as a foundation to perform medical imaging informatics research in developing decision-support tools and knowledge base for future data mining applications.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeon, J., E-mail: jaechun1@ualberta.ca; Alagoz, H. S.; Jung, J., E-mail: jjung@ualberta.ca

Colossal in-plane anisotropic magnetoresistance (AMR) of >16 000% has been engineered in spatially confined La{sub 0.3}Pr{sub 0.4}Ca{sub 0.3}MnO{sub 3} films. Recalling that typical AMR values in films are only a few percent, these results mark an astonishing increase that might potentially lead to fabrication of manganite-based switching and sensor devices. The unique colossal behavior is discussed within the context of anisotropic domain growth.

Flashback Flame Arrester Devices for Fuel Cargo Tank Vapor Vents.

DTIC Science & Technology

1981-03-01

821711ff’erent fuiel/air mixtures: t pr duca-e f-ames with speedis representative :’ th ’se Or cc fuels that c, aid be carried as bulk car , ab atar -i typical...F w Physical Chemistry , Vol. ,o8, pp. 7-101h, 1977. 1 9 . PAPA/Lewis Research Stafl’, Ba.; i(’ si de tr irot tos ’ ly,]rocarbon Fuels with Air, NACA

Paving the way to a full chip gate level double patterning application

NASA Astrophysics Data System (ADS)

Haffner, Henning; Meiring, Jason; Baum, Zachary; Halle, Scott

2007-10-01

Double patterning lithography processes can offer significant yield enhancement for challenging circuit designs. Many decomposition (i.e. the process of dividing the layout design into first and second exposures) techniques are possible, but the focus of this paper is on the use of a secondary "cut" mask to trim away extraneous features left from the first exposure. This approach has the advantage that each exposure only needs to support a subset of critical features (e.g. dense lines with the first exposure, isolated spaces with the second one). The extraneous features ("printing assist features" or PrAFs) are designed to support the process window of critical features much like the role of the subresolution assist features (SRAFs) in conventional processes. However, the printing nature of PrAFs leads to many more design options, and hence a greater process and decomposition parameter exploration space, than are available for SRAFs. A decomposition scheme using PRAFs was developed for a gate level process. A critical driver of the work was to deliver improved across-chip linewidth variation (ACLV) performance versus an optimized single exposure process while providing support for a larger range of critical features. A variety of PRAF techniques were investigated by simulation, with a PrAF scheme similar to standard SRAF rules being chosen as the optimal solution [1]. This paper discusses aspects of the code development for an automated PrAF generation and placement scheme and the subsequent decomposition of a layout into two mask levels. While PrAF placement and decomposition is straightforward for layouts with pitch and orientation restrictions, it becomes rather complex for unrestricted layout styles. Because this higher complexity yields more irregularly shaped PrAFs, mask making becomes another critical driver of the optimum placement and clean-up strategies. Examples are given of how those challenges are met or can be successfully circumvented. During subsequent decomposition of the PrAF-enhanced layout into two independent mask levels, various geometric decomposition parameters have to be considered. As an example, the removal of PrAFs has to be guaranteed by a minimum required overlap of the cut mask opening past any PrAF edge. It is discussed that process assumptions such as CD tolerances and overlay as well as inter-level relationship ground rules need to be considered to successfully optimize the final decomposition scheme. Furthermore, simulation and experimental results regarding not only ACLV but also across-device linewidth variation (ADLV) are analyzed.

Flexible graphene-PZT ferroelectric nonvolatile memory.

PubMed

Lee, Wonho; Kahya, Orhan; Toh, Chee Tat; Ozyilmaz, Barbaros; Ahn, Jong-Hyun

2013-11-29

We report the fabrication of a flexible graphene-based nonvolatile memory device using Pb(Zr0.35,Ti0.65)O3 (PZT) as the ferroelectric material. The graphene and PZT ferroelectric layers were deposited using chemical vapor deposition and sol–gel methods, respectively. Such PZT films show a high remnant polarization (Pr) of 30 μC cm−2 and a coercive voltage (Vc) of 3.5 V under a voltage loop over ±11 V. The graphene–PZT ferroelectric nonvolatile memory on a plastic substrate displayed an on/off current ratio of 6.7, a memory window of 6 V and reliable operation. In addition, the device showed one order of magnitude lower operation voltage range than organic-based ferroelectric nonvolatile memory after removing the anti-ferroelectric behavior incorporating an electrolyte solution. The devices showed robust operation in bent states of bending radii up to 9 mm and in cycling tests of 200 times. The devices exhibited remarkable mechanical properties and were readily integrated with plastic substrates for the production of flexible circuits.

Devices capable of removing silicon and aluminum from gaseous atmospheres

DOEpatents

Spengler, Charles J.; Singh, Prabhakar

1989-01-01

An electrochemical device is made of a containment vessel (30) optional ceramic material within the containment vessel and including one or more electrochemical cells (10), the cells containing a porous exposed electrode (11) in contact with a solid electrolyte, where at least one of the exposed electrode, the containment vessel, and the optional ceramic material contains a deposit selected from metal oxide and metal salt capable of forming a metal oxide upon heating, where the metal is selected from the group consisting of Ce, Sm, Mg, Be, Ca, Sr, Ti, Zr, Hf, Y, La, Pr, Nb, Pm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Th, U, and their mixtures.

Commutation assistée, des machines à courant continu

NASA Astrophysics Data System (ADS)

Goyet, R.; Benalla, H.

1994-12-01

The paper presents an experiment of DC machine (135V, 60A, 8kW) working without commutating poles. These have the usual function of implementing the commutation of sections as they pass trough the neutral line. It is a question of reversing the section current in front of the brushes. Commutating poles are generally bulky and increase perceptibly heaviness of the machine (of 1/5about). In the following experiment they are suppressed and commutation is carried out from the outside of the machine owing to an electronic device. Working of this electronic assistance has been described in a previous paper. Here, in this second paper, two different devices are implemented until three quarters of nominal values of the machine ; accurate control of the devices is made easier by means of a computer. Experiment has been implemented without any spark under the brushes, it confirms the feasibility of a new way of commutation for DC machines. These devices do not make yet an industrial way of suppressing commutating poles. On the other hand they lead to an original point of view about commutation phenomena. They set a new process using both the cutting off capability of brushes and the accurate adjustements of power electronics. Nous présentons ici une expérimentation d'une machine à courant continu de puissance 8 kW (135 V, 60 A) fonctionnant sans pôles auxiliaires. Rappelons que ces derniers ont pour fonction habituelle d'assurer la commutation des sections à leur passage sur la ligne neutre. Il s'agit d'inverser le courant dans la section lorsqu'elle passe devant les balais. Les pôles auxiliaires sont en général encombrants et augmentent sensiblement le poids de la machine (de 1/5 environ). Dans l'expérience présentée ici ils sont supprimés et la commutation est réalisée à l'extérieur de la machine grâce à un dispositif électronique appelé ll d'assistance gg. Dans un précédent article [1] nous avons donné le principe de fonctionnement de cette assistance. Dans ce deuxième article nous présentons les résultats obtenus sur une machine à l'aide de deux dispositifs électroniques différents pilotés par ordinateur. Cette machine a fonctionné, sans génération d'arc, à trois quarts de sa puissance nominale. L'expérience confirme les possibilités de la commutation assistée par électronique. Les dispositifs utilisés ne constituent pas encore une solution industriellement viable en remplacement du pôle auxiliaire. Ils permettent par contre d'appréhender de façon originale les phénomènes de commutation. Il s'agit d'un procédé nouveau, utilisant à la fois le pouvoir de coupure des balais et les possibilités de réglage fin de l'électronique de puissance.

Enhanced UVB emission and analysis of chemical states of Ca5(PO4)3OH:Gd3+,Pr3+ phosphor prepared by co-precipitation

NASA Astrophysics Data System (ADS)

Mokoena, P. P.; Nagpure, I. M.; Kumar, Vinay; Kroon, R. E.; Olivier, E. J.; Neethling, J. H.; Swart, H. C.; Ntwaeaborwa, O. M.

2014-08-01

Hydroxyapatite (Ca5(PO4)3OH) is a well-known bioceramic material used in medical applications because of its ability to form direct chemical bonds with living tissues. This mineral is currently used as a host for rare-earth ions (e.g. Gd3+, Pr3+, Tb3+, etc.) to prepare phosphors that can be used in light emitting devices of different types. In this study Ca5(PO4)3OH:Gd3+,Pr3+ phosphors were prepared by the co-precipitation method and were characterised by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, high resolution transmission electron microscopy, energy dispersive x-ray spectroscopy and photoluminescence spectroscopy. The x-ray diffraction pattern was consistent with the hexagonal phase of Ca5(PO4)3OH referenced in JCPDS card number 73-0293. The x-ray photoelectron spectroscopy data indicated that Ca2+ occupied two different lattice sites, referred to as Ca1 and Ca2. The photoluminescence data exhibited a narrowband emission located at 313 nm, which is associated with the 6P7/2→8S7/2 transition of the Gd3+ ion. This emission is classified as ultraviolet B and it is suitable for use in phototherapy lamps to treat various skin diseases. The photoluminescence intensity of the 313 nm emission was enhanced considerably by Pr3+ co-doping.

Clinical Verification of Image Warping as a Potential Aid for the Visually Handicapped

NASA Technical Reports Server (NTRS)

Loshin, David

1996-01-01

The bulk of this research was to designed determine potential of the Programmable Remapper (PR) as a device to enhance vision for the visually handicapped. This research indicated that remapping would have potential as a low vision device if the eye position could be monitored with feedback to specify the proper location of the remapped image. This must be accomplished at high rate so that there is no lag of the image behind the eye position. Since at this time, there is no portable eye monitor device (at a reasonable cost) that will operate under the required conditions, it would not be feasible to continue with remapping experiments for patients with central field defects. However, since patients with peripheral field defects do not have the same eye positioning requirements, they may indeed benefit from this technology. Further investigations must be performed to determine plausibility of this application of remapping.

Simulation Experiments of Reacting Two-Phase Flow

DTIC Science & Technology

1987-04-06

to 50 % of the lower gas explosion limit (4 % ofhydrogen in the surrounding air ). Then, this device automatically stops the filling procedure...and the discharge of the rifle into air 68 36. Final chamber pressure versus time (Charge pr’,ssure P, = 12 MPa; closed bomb mode) 70 37. Final...surrounding air , which is entrained turbulently, a combustion process can take place that results in a high intensity flash, called muzzle flash [6

Joint Services Electronics Program.

DTIC Science & Technology

1981-09-30

devices and a structure in which an interrupted superconduc- tive film strip lies on a highly doped silicon surface. We have also developed a strong...Slusher, and H. Sturge, reported at 2nd Int’l Conf. on Submillimeter Waves and Their Applications, San Juan , P.R., December 1967. (12) T. DeGraauw, H... lies in the noncommutative property of matrix multiplication. However, we believe that techniques can be developed to deal with special classes of non

Study of true-remanent polarization using remanent hysteresis task and resistive leakage analysis in ferroelectric 0.64Pb(Mg1/3Nb2/3)O3-0.36PbTiO3 ceramics

NASA Astrophysics Data System (ADS)

Joseph, Abhilash J.; Kumar, Binay

2018-03-01

The conventionally reported value of remanent polarization (Pr) contains contribution from non-remanent components which are not usable for memory device applications. This report presents techniques which extract the true-remanent (intrinsic) component of polarization after eliminating the non-remanent component in ferroelectric ceramics. For this, "remanent hysteresis task" and "positive-up-negative-down technique" were performed which utilized the switchable properties of polarizations to nullify the contributions from the non-remanent (non-switchable) components. The report also addresses the time-dependent leakage behavior of the ceramics focusing on the presence of resistive leakage (a time-dependent parameter) present in the ceramics. The techniques presented here are especially useful for polycrystalline ceramics where leakage current leads to an erroneous estimation of Pr.

Controlling the photoconductivity: Graphene oxide and polyaniline self assembled intercalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vempati, Sesha, E-mail: svempati01@qub.ac.uk; Ozcan, Sefika; Department of Polymer Science and Technology, Middle East Technical University, Ankara 06800

2015-02-02

We report on controlling the optoelectronic properties of self-assembled intercalating compound of graphene oxide (GO) and HCl doped polyaniline (PANI). Optical emission and X-ray diffraction studies revealed a secondary doping phenomenon of PANI with –OH and –COOH groups of GO, which essentially arbitrate the intercalation. A control on the polarity and the magnitude of the photoresponse (PR) is harnessed by manipulating the weight ratios of PANI to GO (viz., 1:1.5 and 1:2.2 are abbreviated as PG1.5 and PG2.2, respectively), where ±PR = 100(R{sub Dark} – R{sub UV-Vis})/R{sub Dark} and R corresponds to the resistance of the device in dark or UV-Vis illumination.more » To be precise, the PR from GO, PANI, PG1.5, and PG2.2 are +34%, −111%, −51%, and +58%, respectively.« less

Device Discovery in Frequency Hopping Wireless Ad Hoc Networks

DTIC Science & Technology

2004-09-01

10.1. Benchmark scatternet configuration used for outreach compar- ison. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 10.2. Average...Slave - Slave A B C DE Figure 10.1: Benchmark scatternet configuration used for outreach comparison. Additionally: • All nodes are within range of one...MSTSs ISOM mean = 6.97 MSTSs NISOM mean = 7.21 MSTSs Exponential distribution MSTSs P ic on et A -D p ac ke t g en er at io n ti m e pr ob ab il it y

Evaluation of the Environmental Instruments, Incorporated Series 200 Dual Component Wind Set.

DTIC Science & Technology

1980-09-01

elements is sensed to derive the sign (+ or -), which indicates the wind direction across the element pair. The reference arm of the Wheatstone bridge...Csine a for the crosswind axis, r and PF=a Vw Sine a for the headwind axis, r where Pa is the ambient air density, Pr is reference density at standard...pressure transducer is a hybrid linear silicon device which consists of a diaphragm and pressure reference , piezoresistive sensor, signal discriminator

Microcircuit Reliability Bibliography. Volume 4. 1976 Annual Reference Supplement. (Document Numbers 11045-11745)

DTIC Science & Technology

1976-04-01

State Electron- Res. Lab., Eindhoven, Neth.) icw 16, no. 12, 1315-20, Dec. 1973 ATMOS-AN ELECTRICALLY REPROGRAMMABLE READ-ONLY MEMORY DEVICE. IEEE Trans...transistor is described that can be used nular and array geometry contacts by as an electrically reprogrammable read- the pr~nciple of superposition. It is...digital tuning techniques for FM and typical automobile systems can be readily television, and pocket pagers. Tn. implemented by COS1440S monolithic

Experimental Study on Ultrafine Particle Removal Performance of Portable Air Cleaners with Different Filters in an Office Room

PubMed Central

Ma, Huan; Shen, Henggen; Shui, Tiantian; Li, Qing; Zhou, Liuke

2016-01-01

Size- and time-dependent aerodynamic behaviors of indoor particles, including PM1.0, were evaluated in a school office in order to test the performance of air-cleaning devices using different filters. In-situ real-time measurements were taken using an optical particle counter. The filtration characteristics of filter media, including single-pass efficiency, volume and effectiveness, were evaluated and analyzed. The electret filter (EE) medium shows better initial removal efficiency than the high efficiency (HE) medium in the 0.3–3.5 μm particle size range, while under the same face velocity, the filtration resistance of the HE medium is several times higher than that of the EE medium. During service life testing, the efficiency of the EE medium decreased to 60% with a total purifying air flow of 25 × 104 m3/m2. The resistance curve rose slightly before the efficiency reached the bottom, and then increased almost exponentially. The single-pass efficiency of portable air cleaner (PAC) with the pre-filter (PR) or the active carbon granule filter (CF) was relatively poor. While PAC with the pre-filter and the high efficiency filter (PR&HE) showed maximum single-pass efficiency for PM1.0 (88.6%), PAC with the HE was the most effective at removing PM1.0. The enhancement of PR with HE and electret filters augmented the single-pass efficiency, but lessened the airflow rate and effectiveness. Combined with PR, the decay constant of large-sized particles could be greater than for PACs without PR. Without regard to the lifetime, the electret filters performed better with respect to resource saving and purification improvement. A most penetrating particle size range (MPPS: 0.4–0.65 μm) exists in both HE and electret filters; the MPPS tends to become larger after HE and electret filters are combined with PR. These results serve to provide a better understanding of the indoor particle removal performance of PACs when combined with different kinds of filters in school office buildings. PMID:26742055

A field investigation of a modified intravaginal progesterone releasing device and oestradiol benzoate based ovulation synchronisation protocol designed for fixed-time artificial insemination of Brahman heifers.

PubMed

Edwards, S A A; Boe-Hansen, G B; Satake, N; Chandra, K; McGowan, M R

2015-09-01

Pregnancy rates (PR) to fixed-time AI (FTAI) in Brahman heifers were compared after treatment with a traditional oestradiol-based protocol (OPO-8) or a modified protocol (OPO-6) where the duration of intravaginal progesterone releasing device (IPRD) was reduced from 8 to 6 days, and the interval from IPRD removal to oestradiol benzoate (ODB) was increased from 24 to 36 h. Rising 2 yo heifers on Farm A: (n = 238 and n = 215; two consecutive days AI); B (n = 271); and C (n = 393) were allocated to OPO-8 or OPO-6. An IPRD was inserted and 1mg ODB i.m. on Day 0 for OPO-8 heifers and Day 2 for OPO-6 heifers. On Day 8, the IPRD was removed and 500 μg cloprostenol i.m. At 24h, for OPO-8 heifers, and 36 h, for OPO-6 heifers, post IPRD removal all heifers received 1mg ODB i.m. FTAI was conducted at 54 and 72 h post IPRD removal for OPO-8 and OPO-6 heifers. At Farm A, OPO-6 heifers, AI on the second day, the PR was 52.4% to FTAI (P = 0.024) compared to 36.8% for OPO-8 heifers. However, no differences were found between OPO-8 and OPO-6 protocols at Farm A (first day of AI) (39.9 vs. 35.7%), or Farms B (26.2 vs. 35.4%) and C (43.2% vs. 40.3%). Presence of a corpus luteum at IPRD insertion affected PR to FTAI (43.9% vs. 28.8%; P < 0.001). This study has shown that the modified ovulation synchronisation protocol OPO-6 may be a viable alternative to the OPO-8 protocol for FTAI in B. indicus heifers. Copyright © 2015 Elsevier B.V. All rights reserved.

Programming Cardiac Resynchronization Therapy for Electrical Synchrony: Reaching Beyond Left Bundle Branch Block and Left Ventricular Activation Delay.

PubMed

Varma, Niraj; O'Donnell, David; Bassiouny, Mohammed; Ritter, Philippe; Pappone, Carlo; Mangual, Jan; Cantillon, Daniel; Badie, Nima; Thibault, Bernard; Wisnoskey, Brian

2018-02-06

QRS narrowing following cardiac resynchronization therapy with biventricular (BiV) or left ventricular (LV) pacing is likely affected by patient-specific conduction characteristics (PR, qLV, LV-paced propagation interval), making a universal programming strategy likely ineffective. We tested these factors using a novel, device-based algorithm (SyncAV) that automatically adjusts paced atrioventricular delay (default or programmable offset) according to intrinsic atrioventricular conduction. Seventy-five patients undergoing cardiac resynchronization therapy (age 66±11 years; 65% male; 32% with ischemic cardiomyopathy; LV ejection fraction 28±8%; QRS duration 162±16 ms) with intact atrioventricular conduction (PR interval 194±34, range 128-300 ms), left bundle branch block, and optimized LV lead position were studied at implant. QRS duration (QRSd) reduction was compared for the following pacing configurations: nominal simultaneous BiV (Mode I: paced/sensed atrioventricular delay=140/110 ms), BiV+SyncAV with 50 ms offset (Mode II), BiV+SyncAV with offset that minimized QRSd (Mode III), or LV-only pacing+SyncAV with 50 ms offset (Mode IV). The intrinsic QRSd (162±16 ms) was reduced to 142±17 ms (-11.8%) by Mode I, 136±14 ms (-15.6%) by Mode IV, and 132±13 ms (-17.8%) by Mode II. Mode III yielded the shortest overall QRSd (123±12 ms, -23.9% [ P <0.001 versus all modes]) and was the only configuration without QRSd prolongation in any patient. QRS narrowing occurred regardless of QRSd, PR, or LV-paced intervals, or underlying ischemic disease. Post-implant electrical optimization in already well-selected patients with left bundle branch block and optimized LV lead position is facilitated by patient-tailored BiV pacing adjusted to intrinsic atrioventricular timing using an automatic device-based algorithm. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Rapid and Highly Sensitive Detection of Variant Creutzfeldt - Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies

PubMed Central

Belondrade, Maxime; Nicot, Simon; Béringue, Vincent; Coste, Joliette; Lehmann, Sylvain; Bougard, Daisy

2016-01-01

The prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE) by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA) technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA). This assay allowed the specific detection of minute quantities (10−8 brain dilution) of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions. PMID:26800081

Interfacial rheology of model particles at liquid interfaces and its relation to (bicontinuous) Pickering emulsions

NASA Astrophysics Data System (ADS)

Thijssen, J. H. J.; Vermant, J.

2018-01-01

Interface-dominated materials are commonly encountered in both science and technology, and typical examples include foams and emulsions. Conventionally stabilised by surfactants, emulsions can also be stabilised by micron-sized particles. These so-called Pickering-Ramsden (PR) emulsions have received substantial interest, as they are model arrested systems, rather ubiquitous in industry and promising templates for advanced materials. The mechanical properties of the particle-laden liquid-liquid interface, probed via interfacial rheology, have been shown to play an important role in the formation and stability of PR emulsions. However, the morphological processes which control the formation of emulsions and foams in mixing devices, such as deformation, break-up, and coalescence, are complex and diverse, making it difficult to identify the precise role of the interfacial rheological properties. Interestingly, the role of interfacial rheology in the stability of bicontinuous PR emulsions (bijels) has been virtually unexplored, even though the phase separation process which leads to the formation of these systems is relatively simple and the interfacial deformation processes can be better conceptualised. Hence, the aims of this topical review are twofold. First, we review the existing literature on the interfacial rheology of particle-laden liquid interfaces in rheometrical flows, focussing mainly on model latex suspensions consisting of polystyrene particles carrying sulfate groups, which have been most extensively studied to date. The goal of this part of the review is to identify the generic features of the rheology of such systems. Secondly, we will discuss the relevance of these results to the formation and stability of PR emulsions and bijels.

Integration of strained and relaxed silicon thin films on silicon wafers via engineered oxide heterostructures: Experiment and theory

NASA Astrophysics Data System (ADS)

Seifarth, O.; Dietrich, B.; Zaumseil, P.; Giussani, A.; Storck, P.; Schroeder, T.

2010-10-01

Strained and relaxed single crystalline Si on insulator systems is an important materials science approach for future Si-based nanoelectronics. Layer transfer techniques are the dominating global integration approach over the whole wafer system but are difficult to scale down for local integration purposes limited to the area of the future device. In this respect, the heteroepitaxy approach by two simple subsequent epitaxial deposition steps of the oxide and the Si thin film is a promising way. We introduce tailored (Pr2O3)1-x(Y2O3)x oxide heterostructures on Si(111) as flexible heteroepitaxy concept for the integration of either strained or fully relaxed single crystalline Si thin films. Two different buffer concepts are explored by a combined experimental and theoretical study. First, the growth of fully relaxed single crystalline Si films is achieved by the growth of mixed PrYO3 insulators on Si(111) whose lattice constant is matched to Si. Second, isomorphic oxide-on-oxide epitaxy is exploited to grow strained Si films on lattice mismatched Y2O3/Pr2O3/Si(111) support systems. A thickness dependent multilayer model, based on Matthew's approach for strain relaxation by misfit dislocations, is presented to describe the experimental data.

Consumer Sleep Technologies: A Review of the Landscape

PubMed Central

Ko, Ping-Ru T.; Kientz, Julie A.; Choe, Eun Kyoung; Kay, Matthew; Landis, Carol A.; Watson, Nathaniel F.

2015-01-01

Objective: To review sleep related consumer technologies, including mobile electronic device “apps,” wearable devices, and other technologies. Validation and methodological transparency, the effect on clinical sleep medicine, and various social, legal, and ethical issues are discussed. Methods: We reviewed publications from the digital libraries of the Association for Computing Machinery, Institute of Electrical and Electronics Engineers, and PubMed; publications from consumer technology websites; and mobile device app marketplaces. Search terms included “sleep technology,” “sleep app,” and “sleep monitoring.” Results: Consumer sleep technologies are categorized by delivery platform including mobile device apps (integrated with a mobile operating system and utilizing mobile device functions such as the camera or microphone), wearable devices (on the body or attached to clothing), embedded devices (integrated into furniture or other fixtures in the native sleep environment), accessory appliances, and conventional desktop/website resources. Their primary goals include facilitation of sleep induction or wakening, self-guided sleep assessment, entertainment, social connection, information sharing, and sleep education. Conclusions: Consumer sleep technologies are changing the landscape of sleep health and clinical sleep medicine. These technologies have the potential to both improve and impair collective and individual sleep health depending on method of implementation. Citation: Ko PR, Kientz JA, Choe EK, Kay M, Landis CA, Watson NF. Consumer sleep technologies: a review of the landscape. J Clin Sleep Med 2015;11(12):1455–1461. PMID:26156958

A single-phase white light emitting Pr3+ doped Ba2CaWO6 phosphor: synthesis, photoluminescence and optical properties

NASA Astrophysics Data System (ADS)

Sreeja, E.; Vidyadharan, Viji; Jose, Saritha K.; George, Anns; Joseph, Cyriac; Unnikrishnan, N. V.; Biju, P. R.

2018-04-01

Pr3+ doped Ba2CaWO6 phosphor were prepared by traditional high-temperature solid-state reaction technique. The structure evolution was systematically investigated by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis. The X-ray powder diffraction patterns indicate that the prepared phosphors crystallized in the cubic double-perovskite structure. The functional groups were identified using FTIR spectra and the elements present in the composition were confirmed by the EDS profile. The morphology of the phosphor was identified using SEM and TEM analysis. The PL spectra illustrated that these phosphors could be efficiently excited by charge transfer band of host and the maximum luminescence intensity was observed at 0.06 wt% of Pr3+ ion. Upon the charge transfer band excitation, emission spectra showed peaks at 489, 532, 647, 685 and 737 nm corresponding to 3P0→3H4, 3P1→3H5, 3P0→3F2, 3P0→3F3 and 3P0→3F4 transitions respectively. The concentration quenching of Ba2CaWO6:Pr3+ phosphor can be mainly attributed to dipole-dipole interaction. The CIE coordinates were estimated to be close to the white region. The decay curves are well fitted with double exponential decay models. The standard and modified Judd-Ofelt (JO) theories were used to determine the Judd-Ofelt intensity parameters, radiative transition probabilities and branching ratios. The optical properties indicate that Ba2CaWO6:Pr3+ phosphors can produce white light emission from a single phase host and its potential application for solid-state lighting and display devices.

Effect of pH on rheotaxis of bull sperm using microfluidics.

PubMed

El-Sherry, T M; Abdel-Ghani, M A; Abou-Khalil, N S; Elsayed, M; Abdelgawad, M

2017-10-01

The aim of the present research is to study the effect of pH values on the sperm rheotaxis properties. Semen collected from bulls was diluted with SOF medium (1:10). pH of the medium was adjusted using a digital pH meter to the following pH values: 6.0, 6.2, 6.4, 6.4, 6.8, 7.0. All kinetic parameters of sperm (n = 3,385) were determined through a computer-assisted sperm analysis (CASA) system using microfluidic devices with controlled flow velocity. The following parameters were determined: total motility (TM%), positive rheotaxis (PR%), straightline velocity (VSL, μm/s), average path velocity (VAP, μm/s), linearity (LIN, as VSL/VCL, %), beat cross-frequency (BCF, Hz) and curvilinear velocity (VCL, μm/s). Nitric oxide, calcium and potassium were estimated in semen at different pH values. To confirm the effect of nitric oxide and K + , we used sodium nitroprusside (an NO donor) and KCL as (a K + donor) to see their effect on sperm PR%. The results showed no difference in TM% at pH (6-7). The PR% was the lowest at pH 6 and 7. The best parameters for the PR% were at pH 6.4-6.6. The concentration of Ca +2 did not change at different pH values. The mean NO values decreased with the increase of pH; however, the mean values of K + increased with the increase of pH. Addition of high concentration of NO and K + to the semen media at fixed pH level had a negative effect on TM% and PR%. In conclusion, the bull sperm had the best rheotaxis properties at pH 6.4-6.6 and sensitive to the change of seminal NO and K + . © 2017 Blackwell Verlag GmbH.

Topical Meeting on Picosecond Electronics and Optoelectronics

DTIC Science & Technology

1987-10-10

Gee, G. D Thurmond, H. W 8-00 AM (Invited Paper) Yen, Hughes Research Laboratories Design and fabrica- FA1 High-Speed Phenomena In GaAs Quantum Wells...D.H. Auston, P.R. Smith, J.C. Bean, J.P. Harbison, and D. Kaplan , "Picosecond Photoconciuctivity in Amorphous Silicon," in Picosecond Phenomena 1980... FA1 -4 QUANTUM-WELL PHYSICS AND DEVICES C. Weisbuch, Thomson CSF, Presider IA 155 , ,Ii : Al-1 High-Speed Phenomena in GaAs Multiple-Quantum-Wells A

[Ultraviolet exposure from indoor tanning devices as a potential source of health risks: Basic knowledge of the proper use of these devices for practical users, physicians and solarium staff].

PubMed

Malinowska-Borowska, Jolanta; Janosik, Elżbieta

2017-07-26

Bearing in mind the adverse health effects of exposure to ultraviolet (UV) radiation in solarium, especially the risk of carcinogenesis, there is a need to adopt legal regulations by relevant Polish authorities. They should set out the principles for indoor tanning studios operation, supervision and service of the technical parameters of tanning devices and training programs to provide the staff with professional knowledge and other aspects of safety in these facilities. The mechanism of the harmful effects of ultraviolet radiation on the human body, scale of overexposure, resulting from excessive sunbathing are described. Methods for estimating UV exposure and possible actions aimed at reducing the overexposure and preventing from cancer development caused by UV are also presented in this paper. Med Pr 2017;68(5):653-665. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Light-Induced Gelling in a Micellar Fluid Based on a Zwitterionic Surfactant.

NASA Astrophysics Data System (ADS)

Kumar, Rakesh; Raghavan, Srinivasa

2007-03-01

Fluids with photoresponsive rheological properties (i.e. photorheological or PR fluids) can be useful in a range of applications, such as in dampers, sensors, and valves for microfluidic or MEMS devices. Previously, we have demonstrated a cationic surfactant-based PR fluid whose viscosity can be rapidly decreased by UV irradiation. This viscosity decrease was not reversible. Here, we describe a different formulation based on a zwitterionic surfactant that shows a rapid increase in viscosity (gelling) upon exposure to UV radiation. The formulation consists of the zwitterionic surfactant and a photosensitive cinnamic acid derivative. Initially, the viscosity of the fluid is low indicating the presence of small micelles. Upon UV irradiation, the cinnamic acid derivative is photoisomerized from trans to cis. In turn, the small micelles transform into long wormlike micelles, thus increasing the solution viscosity by more than five orders of magnitude. Small angle neutron scattering (SANS) data confirms the dramatic increase in micelle length. Possible reasons for such changes in micelle dimensions will be discussed.

Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

PubMed

Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

2017-10-01

Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

Contraception use and unplanned pregnancies among injection drug-using women in St Petersburg, Russia.

PubMed

Abdala, Nadia; Kershaw, Trace; Krasnoselskikh, Tatiana V; Kozlov, Andrei P

2011-07-01

This cross-sectional study estimated the prevalence of contraceptive methods and investigated whether abortion rates influence contraceptive behaviour among injection drug-using (IDU) women in St Petersburg, Russia. A self-administered questionnaire of behaviour in the last 3 months was applied to a convenient sample of IDU women. Of 80 sexually active participants, 67% had had an abortion. No participant reported using hormonal contraceptives or intrauterine devices (IUDs). The only valid method of contraception used was condoms, which was reported by half of the participants. Consistent condom use was reported by 22% of participants and was no more likely among those who had an abortion. Condom use was significantly associated with having multiple or casual sex partners [prevalence ratio (PR) 1.75, 95% (confidence interval) CI 1.11-2.78, p = 0.01], having an IDU sex partner (PR 0.55, 95% CI 0.36-0.85, p = 0.029) and with a negative attitude toward condoms (PR 0.53, 95% CI 0.33-0.84, p = 0.01). Abortions were less likely among those who had multiple or casual sex partners (PR 0.69, 95% CI 0.49-0.97, p = 0.03). Despite the high prevalence of abortions among IDU women, none reported the use of hormonal contraception or IUDs. Having had an abortion was not associated with greater likelihood of using condoms. Participants mostly used condoms with casual or multiple sex partners, suggesting that condoms were used mainly to prevent HIV/sexually transmitted infection transmission and not to prevent pregnancy. Programmes to prevent unwanted pregnancies and reduce abortion-related health risks among this understudied vulnerable group are needed.

High-performance varistors simply by hot-dipping zinc oxide thin films in Pr6O11: Influence of temperature

PubMed Central

Wang, Yang; Peng, Zhijian; Wang, Qi; Wang, Chengbiao; Fu, Xiuli

2017-01-01

High-performance ZnO-Pr6O11 thin-film varistors were fabricated simply by hot-dipping oxygen-deficient zinc oxide thin films in Pr6O11 powder. The films had a composition of ZnO0.81 and a thickness of about 200 nm, which were deposited by radio frequency magnetron sputtering a sintered zinc oxide ceramic target. Special attention was paid on the temperature dependence of the varistors. In 50 min with hot-dipping temperature increased from 300–700 °C, the nonlinear coefficient (α) of the varistors increased, but with higher temperature it decreased again. Correspondingly, the leakage current (IL) decreased first and then increased, owing mainly to the formation and destroying of complete zinc oxide/Pr6O11 grain boundaries. The breakdown field (E1mA) decreased monotonously from 0.02217 to 0.01623 V/nm with increasing temperature (300–800 °C), due to the decreased number of effective grain boundaries in the varistors. The varistors prepared at 700 °C exhibited the optimum nonlinear properties with the highest α = 39.29, lowest IL = 0.02736 mA/cm2, and E1mA = 0.01757 V/nm. And after charge-discharge at room temperature for 1000 times, heating at 100 or 250 °C for up to 100 h, or applying at up to 250 °C, the varistors still performed well. Such nanoscaled thin-film varistors will be very promising in electrical/electronic devices working at low voltage. PMID:28155890

A novel methodology for litho-to-etch pattern fidelity correction for SADP process

NASA Astrophysics Data System (ADS)

Chen, Shr-Jia; Chang, Yu-Cheng; Lin, Arthur; Chang, Yi-Shiang; Lin, Chia-Chi; Lai, Jun-Cheng

2017-03-01

For 2x nm node semiconductor devices and beyond, more aggressive resolution enhancement techniques (RETs) such as source-mask co-optimization (SMO), litho-etch-litho-etch (LELE) and self-aligned double patterning (SADP) are utilized for the low k1 factor lithography processes. In the SADP process, the pattern fidelity is extremely critical since a slight photoresist (PR) top-loss or profile roughness may impact the later core trim process, due to its sensitivity to environment. During the subsequent sidewall formation and core removal processes, the core trim profile weakness may worsen and induces serious defects that affect the final electrical performance. To predict PR top-loss, a rigorous lithography simulation can provide a reference to modify mask layouts; but it takes a much longer run time and is not capable of full-field mask data preparation. In this paper, we first brought out an algorithm which utilizes multi-intensity levels from conventional aerial image simulation to assess the physical profile through lithography to core trim etching steps. Subsequently, a novel correction method was utilized to improve the post-etch pattern fidelity without the litho. process window suffering. The results not only matched PR top-loss in rigorous lithography simulation, but also agreed with post-etch wafer data. Furthermore, this methodology can also be incorporated with OPC and post-OPC verification to improve core trim profile and final pattern fidelity at an early stage.

Validation protocols for blood pressure-measuring devices: status quo and development needs.

PubMed

Beime, Beate; Deutsch, Cornelia; Gomez, Timothy; Zwingers, Thomas; Mengden, Thomas; Bramlage, Peter

2016-02-01

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Therefore, blood pressure self-measuring devices have emerged as valuable tools in patient care and the accuracy of these instruments is of fundamental importance. For this reason, several validation procedures for assessing the efficacy of blood pressure monitoring devices have been developed, including protocols by the Association for the Advancement of Medical Instrumentation, the British Hypertension Society, the German Hypertension League (Prüfsiegelprotokoll), and the International Protocol of the Working Group on Blood Pressure Monitoring of the European Society of Hypertension. In the past, most of the protocols have been reviewed and modified because of experiences gained during the validation studies carried out. However, each shows distinct differences, that is number and characteristics of patients required, blood pressure ranges, and the length of the validation procedure, which may result in unique advantages and/or limitations associated with their use. The continued standardization and evolution of these guidelines is essential to ensure the efficacy of blood pressure-measuring devices marketed for clinical and home use. Here, we aimed to compare four currently used validation protocols and to initiate a discussion on potential future improvements.

Identification and characterisation of seventeen glutathione S-transferase genes from the cabbage white butterfly Pieris rapae.

PubMed

Liu, Su; Zhang, Yu-Xing; Wang, Wen-Long; Zhang, Bang-Xian; Li, Shi-Guang

2017-11-01

Insect glutathione S-transferases (GSTs) play essential roles in the detoxification of insecticides and other xenobiotic compounds. The cabbage white butterfly, Pieris rapae, is an economically important agricultural pest. In this study, 17 cDNA sequences encoding putative GSTs were identified in P. rapae. All cDNAs include a complete open reading frame and were designated PrGSTd1-PrGSTz2. Based on phylogenetic analysis, PrGSTs were divided into six classes (delta, epsilon, omega, sigma, theta and zeta). The exon-intron organizations of these PrGSTs were also analysed. Recombinant proteins of eight PrGSTs (PrGSTD1, PrGSTD2, PrGSTE1, PrGSTE2, PrGSTO1, PrGSTS1, PrGSTT1 and PrGSTZ1) were heterologously expressed in Escherichia coli, and all of these proteins displayed glutathione-conjugating activity towards 1-chloro-2,4-dinitrobenzene (CDNB). Expression patterns in various larval tissues, at different life stages, and following exposure to sublethal doses of abamectin, chlorantraniliprole or lambda-cyhalothrin were determined by reverse transcription-quantitative PCR. The results showed that PrGSTe3, PrGSTs1, PrGSTs2, and PrGSTs4 were mainly transcribed in the fat body, while PrGSTe2 was expressed predominantly in the Malpighian tubules. Four genes (PrGSTe2, PrGSTo4, PrGSTs4 and PrGSTt1) were mainly expressed in fourth-instar larvae, while others were ubiquitously expressed in egg, larval, pupa and/or adult stages. Abamectin treatment significantly upregulated ten genes (PrGSTd1, PrGSTd3, PrGSTe1, PrGSTe2, PrGSTo1, PrGSTo3, PrGSTs1, PrGSTs3, PrGSTs4 and PrGSTt1). Chlorantraniliprole and lambda-cyhalothrin treatment significantly upregulated nine genes (PrGSTd1, PrGSTd2, PrGSTe1, PrGSTe2, PrGSTe3, PrGSTs1, PrGSTs3, PrGSTs4 and PrGSTz1) and ten genes (PrGSTd1, PrGSTd3, PrGSTe1, PrGSTe2, PrGSTo1, PrGSTo2, PrGSTs1, PrGSTs2, PrGSTs3 and PrGSTz2), respectively. These GSTs are potentially involved in the detoxification of insecticides. Copyright © 2017 Elsevier Inc. All rights reserved.

Proceedings of 16th Nordic Semiconductor Meeting Held in Laugarvatn, Iceland on 12-15 June 1994

DTIC Science & Technology

1995-01-10

uniform and is a Recent work [1] by Thomas, Pr~tre and this author on sensitive function of the AB-flux. The nonuniform density the admittance of... LWIR window), are more Fig. 1. Energy band structure of a GaAs/AIGaAs quantum well (QW). difficult to grow, process and fabricate into uniform devices...technology is a viable candidate for large, high per- formance, low cost LWIR (8-12 gm) focal plane arrays (FPAs) [4-6]. CGWX QWIPs operate on account

Buffer layers and articles for electronic devices

DOEpatents

Paranthaman, Mariappan P.; Aytug, Tolga; Christen, David K.; Feenstra, Roeland; Goyal, Amit

2004-07-20

Materials for depositing buffer layers on biaxially textured and untextured metallic and metal oxide substrates for use in the manufacture of superconducting and other electronic articles comprise RMnO.sub.3, R.sub.1-x A.sub.x MnO.sub.3, and combinations thereof; wherein R includes an element selected from the group consisting of La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and Y, and A includes an element selected from the group consisting of Be, Mg, Ca, Sr, Ba, and Ra.

Purification of used eutectic (LiCl-KCl) salt electrolyte from pyroprocessing

NASA Astrophysics Data System (ADS)

Cho, Yung-Zun; Lee, Tae-Kyo; Eun, Hee-Chul; Choi, Jung-Hoon; Kim, In-Tae; Park, Geun-Il

2013-06-01

The separation characteristics of surrogate rare-earth fission products in a eutectic (LiCl-KCl) molten salt were investigated. This system is based on the eutectic salt used for the pyroprocessing treatment of used nuclear fuel (UNF). The investigation was performed using an integrated rare-earth separation apparatus comprising a precipitation reactor, a solid detachment device, and a layer separation device. To separate rare-earth fission products, a phosphate precipitation method using both Li3PO4 and K3PO4 as a precipitant was performed. The use of an equivalent phosphate precipitant composed of 0.408 molar ratio-K3PO4 and 0.592 molar ratio-Li3PO4 can preserve the original eutectic ratio, LiCl-0.592 molar ratio (or 45.2 wt%), as well as provide a high separation efficiency of over 99.5% under conditions of 550 °C and Ar sparging when using La, Nd, Ce, and Pr chlorides. The mixture of La, Nd, Ce, and Pr phosphate had a typical monoclinic (or monazite) structure, which has been proposed as a reliable host matrix for the permanent disposal of a high-level waste form. To maximize the reusability of purified eutectic waste salt after rare-earth separation, the successive rare-earth separation process, which uses both phosphate precipitation and an oxygen sparging method, were introduced and tested with eight rare-earth (Y, La, Ce, Pr, Nd, Sm, Eu and Gd) chlorides. In the successive rare-earth separation process, the phosphate reaction was terminated within 1 h at 550 °C, and a 4-8 h oxygen sparging time were required to obtain over a 99% separation efficiency at 700-750 °C. The mixture of rare-earth precipitates separated by the successive rare-earth separation process was found to be phosphate, oxychloride, and oxide. Through the successive rare-earth separation process, the eutectic ratio of purified salt maintained its original value, and impurity content including the residual precipitant of purified salt can be minimized.

Effect of Pr Valence State on Interfacial Structure and Electrical Properties of Pr Oxide/PrON/Ge Gate Stack Structure

NASA Astrophysics Data System (ADS)

Kato, Kimihiko; Sakashita, Mitsuo; Takeuchi, Wakana; Kondo, Hiroki; Nakatsuka, Osamu; Zaima, Shigeaki

2011-04-01

In this study, we investigated the valence state and chemical bonding state of Pr in a Pr oxide/PrON/Ge structure. We clarified the relationship between the valence state of Pr and the Pr oxide/Ge interfacial reaction using Pr oxide/Ge and Pr oxide/PrON/Ge samples. We found the formation of three Pr oxide phases in Pr oxide films; hexagonal Pr2O3 (h-Pr2O3) (Pr3+), cubic Pr2O3 (c-Pr2O3) (Pr3+), and c-PrO2 (Pr4+). We also investigated the effect of a nitride interlayer on the interfacial reaction in Pr oxide/Ge gate stacks. In a sample with a nitride interlayer (Pr oxide/PrON/Ge), metallic Pr-Pr bonds are also formed in the c-Pr2O3 film. After annealing in H2 ambient, the diffusion of Ge into Pr oxide is not observed in this sample. Pr-Pr bonds probably prevent the interfacial reaction and Ge oxide formation, considering that the oxygen chemical potential of this film is lower than that of a GeO2/Ge system. On the other hand, the rapid thermal oxidation (RTO) treatment terminates the O vacancies and defects in c-Pr2O3. As a result, c-PrO2 with tetravalent Pr is formed in the Pr oxide/PrON/Ge sample with RTO. In this sample, the leakage current density is effectively decreased in comparison with the sample without RTO. Hydrogen termination works effectively in Pr oxide/PrON/Ge samples with and without RTO, and we can achieve an interface state density of as low as 4 ×1011 eV-1·cm-2.

The use of technology to find sexual health information online among men who have sex with men in Hanoi, Vietnam, 2016.

PubMed

Nguyen, Minh X; Krishnan, Aparna; Le, Giang M; Nguyen, Quynh T; Bhadra, Nia M; Nguyen, Sang M; Miller, William C; Go, Vivian F

2018-04-01

In an era where mobile phones and computers are ubiquitous, technology-based interventions to reduce HIV and other sexually transmitted infections (STIs) have great potential to reach high-risk groups, including men who have sex with men (MSM). This study aimed to examine technology usage to find sexual health information online among MSM in Hanoi, Vietnam. A cross-sectional study of 205 MSM in Hanoi was conducted from February to May 2016. Overall, 50.7% of participants reported having used a smartphone, computer, or tablet to find HIV/STI testing locations in the past year, and 75.1% reported having used such devices to find other HIV/STI information online. Unemployment (adjusted prevalence ratio [aPR]: 1.13, 95%CI: 1.00-1.28) and having been tested for HIV (aPR: 1.27, 95%CI: 1.07-1.51) were significantly associated with using technology to find online sexual health information. MSM who had ever exchanged sex for money or drugs (aPR: 0.80; 95%CI: 0.68-0.94) were less likely to use technology to find sexual health information online. Technology is a promising platform for HIV/STI prevention programs among MSM, with the potential to reach different subgroups. Further efforts to develop technology-based interventions tailored to the needs of the MSM communities in Hanoi and to encourage MSM who were not currently seeking sexual health information and testing services online to do so are necessary.

The first prototype of chromatic pupillometer for objective perimetry in retinal degeneration patients

NASA Astrophysics Data System (ADS)

Rotenstreich, Ygal; Chibel, Ron; Haj Yahia, Soad; Achiron, Asaf; Mahajna, Mohamad; Belkin, Michael; Sher, Ifat

2015-03-01

We recently demonstrated the feasibility of quantifying pupil responses (PR) to multifocal chromatic light stimuli for objectively assessing visual field (VF). Here we assessed a second-generation chromatic multifocal pupillometer device with 76 LEDs of 18 degree visual field and a smaller spot size (2mm diameter), aimed of achieving better perimetric resolution. A computerized infrared pupillometer was used to record PR to short- and long-wavelength stimuli (peak 485 nm and 640 nm, respectively) presented by 76 LEDs, 1.8mm spot size, at light intensities of 10-1000 cd/m2 at different points of the 18 degree VF. PR amplitude was measured in 11 retinitis pigmentosa (RP) patients and 20 normal agedmatched controls. RP patients demonstrated statistically significant reduced pupil contraction amplitude in majority of perimetric locations under testing conditions that emphasized rod contribution (short-wavelength stimuli at 200 cd/m2) in peripheral locations (p<0.05). By contrast, the amplitude of pupillary responses under testing conditions that emphasized cone cell contribution (long-wavelength stimuli at 1000 cd/m2) were not significantly different between the groups in majority of perimetric locations, particularly in central locations. Minimal pupil contraction was recorded in areas that were non-detected by chromatic Goldmann. This study demonstrates the feasibility of using pupillometerbased chromatic perimetry for objectively assessing VF defects and retinal function in patients with retinal degeneration. This method may be used to distinguish between the damaged cells underlying the VF defect.

Dielectric, Impedance and Conduction Behavior of Double Perovskite Pr2CuTiO6 Ceramics

NASA Astrophysics Data System (ADS)

Mahato, Dev K.; Sinha, T. P.

2017-01-01

Polycrystalline Pr2CuTiO6 (PCT) ceramics exhibits dielectric, impedance and modulus characteristics as a possible material for microelectronic devices. PCT was synthesized through the standard solid-state reaction method. The dielectric permittivity, impedance and electric modulus of PCT have been studied in a wide frequency (100 Hz-1 MHz) and temperature (303-593 K) range. Structural analysis of the compound revealed a monoclinic phase at room temperature. Complex impedance Cole-Cole plots are used to interpret the relaxation mechanism, and grain boundary contributions towards conductivity have been estimated. From electrical modulus formalism polarization and conductivity relaxation behavior in PCT have been discussed. Normalization of the imaginary part of impedance ( Z″) and the normalized imaginary part of modulus ( M″) indicates contributions from both long-range and localized relaxation effects. The grain boundary resistance along with their relaxation frequencies are plotted in the form of an Arrhenius plot with activation energy 0.45 eV and 0.46 eV, respectively. The ac conductivity mechanism has been discussed.

Solid State Spin-Wave Quantum Memory for Time-Bin Qubits.

PubMed

Gündoğan, Mustafa; Ledingham, Patrick M; Kutluer, Kutlu; Mazzera, Margherita; de Riedmatten, Hugues

2015-06-12

We demonstrate the first solid-state spin-wave optical quantum memory with on-demand read-out. Using the full atomic frequency comb scheme in a Pr(3+):Y2SiO5 crystal, we store weak coherent pulses at the single-photon level with a signal-to-noise ratio >10. Narrow-band spectral filtering based on spectral hole burning in a second Pr(3+):Y2SiO5 crystal is used to filter out the excess noise created by control pulses to reach an unconditional noise level of (2.0±0.3)×10(-3) photons per pulse. We also report spin-wave storage of photonic time-bin qubits with conditional fidelities higher than achievable by a measure and prepare strategy, demonstrating that the spin-wave memory operates in the quantum regime. This makes our device the first demonstration of a quantum memory for time-bin qubits, with on-demand read-out of the stored quantum information. These results represent an important step for the use of solid-state quantum memories in scalable quantum networks.

Numerical characterization of the edge transport conditions and limiter fluxes of the HIDRA stellarator

NASA Astrophysics Data System (ADS)

Marcinko, Steven; Curreli, Davide

2018-02-01

The Hybrid Illinois Device for Research and Applications (HIDRA) is a new device for education and Plasma-Material Interaction research at the University of Illinois at Urbana-Champaign. In advance of its first operational campaign, EMC3-EIRENE simulations have been run on the device. EMC3-EIRENE has been modified to calculate a per-plasma-cell relaxed Bohm-like diffusivity simultaneously with the electron temperature at each iteration. In our characterization, the electron temperature, diffusivity, heat fluxes, and particle fluxes have been obtained for varying power levels on a HIDRA magnetic grid, and scaling laws have been extracted, using constraints from previous experimental data taken when the device was operated in Germany (WEGA facility). Peak electron temperatures and heat fluxes were seen to follow a power-law dependence on the deposited radiofrequency (RF) power of type f (PR F)∝a PRF b , with typical exponents in the range of b ˜0.55 to 0.60. Higher magnetic fields have the tendency to linearize the heat flux dependence on the RF power, with exponents in the range of b ˜ 0.75. Particle fluxes are seen to saturate first, and then slightly decline for RF powers above 120 kW in the low-field case and 180 kW in the high-field case.

PR-PR: Cross-Platform Laboratory Automation System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linshiz, G; Stawski, N; Goyal, G

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Goldenmore » Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.« less

PR-PR: cross-platform laboratory automation system.

PubMed

Linshiz, Gregory; Stawski, Nina; Goyal, Garima; Bi, Changhao; Poust, Sean; Sharma, Monica; Mutalik, Vivek; Keasling, Jay D; Hillson, Nathan J

2014-08-15

To enable protocol standardization, sharing, and efficient implementation across laboratory automation platforms, we have further developed the PR-PR open-source high-level biology-friendly robot programming language as a cross-platform laboratory automation system. Beyond liquid-handling robotics, PR-PR now supports microfluidic and microscopy platforms, as well as protocol translation into human languages, such as English. While the same set of basic PR-PR commands and features are available for each supported platform, the underlying optimization and translation modules vary from platform to platform. Here, we describe these further developments to PR-PR, and demonstrate the experimental implementation and validation of PR-PR protocols for combinatorial modified Golden Gate DNA assembly across liquid-handling robotic, microfluidic, and manual platforms. To further test PR-PR cross-platform performance, we then implement and assess PR-PR protocols for Kunkel DNA mutagenesis and hierarchical Gibson DNA assembly for microfluidic and manual platforms.

Demagnetization of Nd 2Fe 14B, Pr 2Fe 14B, and Sm 2Co 17 Permanent Magnets in Spallation Irradiation Fields

DOE PAGES

Simos, Nikolaos; Ozaki, S.; Mokhov, N.; ...

2018-02-27

Prompted by the need for radiation-resistant permanent magnets for insertion devices (IDs) of high-brilliance next-generation synchrotrons such as the National Synchrotron Light Source II, the demagnetization of Nd 2Fe 14B and Pr 2Fe 14B was studied after exposure to a mixed irradiating field. Degradation and damage of the permanent magnetic material by components of electromagnetic showers induced in magnets by intense high-energy electron beams will alter the magnetic field structure of the IDs. Plate-like Nd 2Fe 14B magnets were irradiated to 1.8 Grad dose and were evaluated against Pr 2Fe 14B magnets irradiated to a lower dose of 20 Mrad.more » In addition, annular Sm 2Co 17 and Nd 2Fe 14B magnets integrated within a ferrofluidic feedthrough (FFFT) rotary seal were also irradiated to dose levels of 2 Grad for Sm 2Co 17 and 20 Mrad for Nd 2Fe 14B. Post-irradiation measurements of the magnetic intensity revealed that severe demagnetization exceeding 85% occurs in Nd 2Fe 14B magnets after only 50 Mrad dose and over 87% for Pr 2Fe 14B after 10 Mrad dose. The annular-shaped Sm 2Co 17 magnets of the FFFTs were almost insensitive to irradiation up to a dose of 2 Grad. Annular-shaped Nd 2Fe 14B magnets also showed resistance to demagnetization, a direct consequence of the annular shape which is characterized by the removal of the stronger demagnetizing field present at the center of a disk-like magnet. As a result, the sensitivity of boron-based permanent magnets to neutron energy (thermal versus fast) was also assessed via specifically designed experiments and discussed.« less

Novel camelid antibody fragments targeting recombinant nucleoprotein of Araucaria hantavirus: a prototype for an early diagnosis of Hantavirus Pulmonary Syndrome.

PubMed

Pereira, Soraya S; Moreira-Dill, Leandro S; Morais, Michelle S S; Prado, Nidiane D R; Barros, Marcos L; Koishi, Andrea C; Mazarrotto, Giovanny A C A; Gonçalves, Giselle M; Zuliani, Juliana P; Calderon, Leonardo A; Soares, Andreimar M; Pereira da Silva, Luiz H; Duarte dos Santos, Claudia N; Fernandes, Carla F C; Stabeli, Rodrigo G

2014-01-01

In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS) is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS) is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N) to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ₈₅) of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ₈₅. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB), surface plasmon resonance (SPR) device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ₈₅ in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with hantavirus infections.

Novel Camelid Antibody Fragments Targeting Recombinant Nucleoprotein of Araucaria hantavirus: A Prototype for an Early Diagnosis of Hantavirus Pulmonary Syndrome

PubMed Central

Pereira, Soraya S.; Moreira-Dill, Leandro S.; Morais, Michelle S. S.; Prado, Nidiane D. R.; Barros, Marcos L.; Koishi, Andrea C.; Mazarrotto, Giovanny A. C. A.; Gonçalves, Giselle M.; Zuliani, Juliana P.; Calderon, Leonardo A.; Soares, Andreimar M.; Pereira da Silva, Luiz H.; Duarte dos Santos, Claudia N.; Fernandes, Carla F. C.; Stabeli, Rodrigo G.

2014-01-01

In addition to conventional antibodies, camelids produce immunoglobulins G composed exclusively of heavy chains in which the antigen binding site is formed only by single domains called VHH. Their particular characteristics make VHHs interesting tools for drug-delivery, passive immunotherapy and high-throughput diagnosis. Hantaviruses are rodent-borne viruses of the Bunyaviridae family. Two clinical forms of the infection are known. Hemorrhagic Fever with Renal Syndrome (HFRS) is present in the Old World, while Hantavirus Pulmonary Syndrome (HPS) is found on the American continent. There is no specific treatment for HPS and its diagnosis is carried out by molecular or serological techniques, using mainly monoclonal antibodies or hantavirus nucleoprotein (N) to detect IgM and IgG in patient serum. This study proposes the use of camelid VHHs to develop alternative methods for diagnosing and confirming HPS. Phage display technology was employed to obtain VHHs. After immunizing one Lama glama against the recombinant N protein (prNΔ85) of a Brazilian hantavirus strain, VHH regions were isolated to construct an immune library. VHHs were displayed fused to the M13KO7 phage coat protein III and the selection steps were performed on immobilized prNΔ85. After selection, eighty clones recognized specifically the N protein. These were sequenced, grouped based mainly on the CDRs, and five clones were analyzed by western blot (WB), surface plasmon resonance (SPR) device, and ELISA. Besides the ability to recognize prNΔ85 by WB, all selected clones showed affinity constants in the nanomolar range. Additionaly, the clone KC329705 is able to detect prNΔ85 in solution, as well as the native viral antigen. Findings support the hypothesis that selected VHHs could be a powerful tool in the development of rapid and accurate HPS diagnostic assays, which are essential to provide supportive care to patients and reduce the high mortality rate associated with hantavirus infections. PMID:25243411

Novel method of optical image registration in wide wavelength range using matrix of piezoelectric crystals

NASA Astrophysics Data System (ADS)

Pigarev, Aleksey V.; Bazarov, Timur O.; Fedorov, Vladimir V.; Ryabushkin, Oleg A.

2018-02-01

Most modern systems of the optical image registration are based on the matrices of photosensitive semiconductor heterostructures. However, measurement of radiation intensities up to several MW/cm2 -level using such detectors is a great challenge because semiconductor elements have low optical damage threshold. Reflecting or absorbing filters that can be used for attenuation of radiation intensity, as a rule, distort beam profile. Furthermore, semiconductor based devices have relatively narrow measurement wavelength bandwidth. We introduce a novel matrix method of optical image registration. This approach doesn't require any attenuation when measuring high radiation intensities. A sensitive element is the matrix made of thin transparent piezoelectric crystals that absorb just a small part of incident optical power. Each crystal element has its own set of intrinsic (acoustic) vibration modes. These modes can be exited due to the inverse piezoelectric effect when the external electric field is applied to the crystal sample providing that the field frequency corresponds to one of the vibration mode frequencies. Such piezoelectric resonances (PR) can be observed by measuring the radiofrequency response spectrum of the crystal placed between the capacitor plates. PR frequencies strongly depend on the crystal temperature. Temperature calibration of PR frequencies is conducted in the uniform heating conditions. In the case a crystal matrix is exposed to the laser radiation the incident power can be obtained separately for each crystal element by measuring its PR frequency kinetics providing that the optical absorption coefficient is known. The operating wavelength range of such sensor is restricted by the transmission bandwidth of the applied crystals. A plane matrix constituting of LiNbO3 crystals was assembled in order to demonstrate the possibility of application of the proposed approach. The crystal elements were placed between two electrodes forming a capacitor which was interconnected to the lock-in detection system. The radiofrequency response to the applied voltage from the generator was measured simultaneously for all elements.

Demagnetization of Nd 2Fe 14B, Pr 2Fe 14B, and Sm 2Co 17 Permanent Magnets in Spallation Irradiation Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simos, Nikolaos; Ozaki, S.; Mokhov, N.

Prompted by the need for radiation-resistant permanent magnets for insertion devices (IDs) of high-brilliance next-generation synchrotrons such as the National Synchrotron Light Source II, the demagnetization of Nd 2Fe 14B and Pr 2Fe 14B was studied after exposure to a mixed irradiating field. Degradation and damage of the permanent magnetic material by components of electromagnetic showers induced in magnets by intense high-energy electron beams will alter the magnetic field structure of the IDs. Plate-like Nd 2Fe 14B magnets were irradiated to 1.8 Grad dose and were evaluated against Pr 2Fe 14B magnets irradiated to a lower dose of 20 Mrad.more » In addition, annular Sm 2Co 17 and Nd 2Fe 14B magnets integrated within a ferrofluidic feedthrough (FFFT) rotary seal were also irradiated to dose levels of 2 Grad for Sm 2Co 17 and 20 Mrad for Nd 2Fe 14B. Post-irradiation measurements of the magnetic intensity revealed that severe demagnetization exceeding 85% occurs in Nd 2Fe 14B magnets after only 50 Mrad dose and over 87% for Pr 2Fe 14B after 10 Mrad dose. The annular-shaped Sm 2Co 17 magnets of the FFFTs were almost insensitive to irradiation up to a dose of 2 Grad. Annular-shaped Nd 2Fe 14B magnets also showed resistance to demagnetization, a direct consequence of the annular shape which is characterized by the removal of the stronger demagnetizing field present at the center of a disk-like magnet. As a result, the sensitivity of boron-based permanent magnets to neutron energy (thermal versus fast) was also assessed via specifically designed experiments and discussed.« less

Cellular Prion Protein Combined with Galectin-3 and -6 Affects the Infectivity Titer of an Endogenous Retrovirus Assayed in Hippocampal Neuronal Cells

PubMed Central

Shin, Hae-Young; Goto, Joy J.; Carp, Richard I.; Choi, Eun-Kyoung; Kim, Yong-Sun

2016-01-01

Prion diseases are infectious and fatal neurodegenerative diseases which require the cellular prion protein, PrPC, for development of diseases. The current study shows that the PrPC augments infectivity and plaque formation of a mouse endogenous retrovirus, MuLV. We have established four neuronal cell lines expressing mouse PrPC, PrP+/+; two express wild type PrPC (MoPrPwild) and the other two express mutant PrPC (MoPrPmut). Infection of neuronal cells from various PrP+/+ and PrP-/- (MoPrPKO) lines with MuLV yielded at least three times as many plaques in PrP+/+ than in PrP-/-. Furthermore, among the four PrP+/+ lines, one mutant line, P101L, had at least 2.5 times as many plaques as the other three PrP+/+ lines. Plaques in P101L were four times larger than those in other PrP+/+ lines. Colocalization of PrP and CAgag was seen in MuLV-infected PrP+/+ cells. In the PrP-MuLV interaction, the involvement of galectin-3 and -6 was observed by immunoprecipitation with antibody to PrPC. These results suggest that PrPC combined with galectin-3 and -6 can act as a receptor for MuLV. P101L, the disease form of mutant PrPC results suggest the genetic mutant form of PrPC may be more susceptible to viral infection. PMID:27936017

Modulation of Progesterone Receptor Isoform Expression in Pregnant Human Myometrium

PubMed Central

2017-01-01

Background. Regulation of myometrial progesterone receptor (PR) expression is an unresolved issue central to understanding the mechanism of functional progesterone withdrawal and initiation of labor in women. Objectives. To determine whether pregnant human myometrium undergoes culture-induced changes in PR isoform expression ex situ and, further, to determine if conditions approaching the in vivo environment stabilise PR isoform expression in culture. Methods. Term nonlaboring human myometrial tissues were cultured under specific conditions: serum supplementation, steroids, stretch, cAMP, PMA, PGF2α, NF-κB inhibitors, or TSA. Following 48 h culture, PR-T, PR-A, and PR-B mRNA levels were determined using qRT-PCR. PR-A/PR-B ratios were calculated. Results. PR-T and PR-A expression and the PR-A/PR-B ratio significantly increased in culture. Steroids prevented the culture-induced increase in PR-T and PR-A expression. Stretch blocked the effects of steroids on PR-T and PR-A expression. PMA further increased the PR-A/PR-B ratio, while TSA blocked culture-induced increases of PR-A expression and the PR-A/PR-B ratio. Conclusion. Human myometrial tissue in culture undergoes changes in PR gene expression consistent with transition toward a laboring phenotype. TSA maintained the nonlaboring PR isoform expression pattern. This suggests that preserving histone and/or nonhistone protein acetylation is critical for maintaining the progesterone dependent quiescent phenotype of human myometrium in culture. PMID:28540297

Investigation of Hotline Allegation of a Questionable Intelligence Activity Concerning the Joint Improvised Explosive Device Defeat Organization (JIEDDO), Counter-IED Operations/Intelligence Integration Center (COIC) (REDACTED)

DTIC Science & Technology

2014-04-04

hlic;hml>nt of the \\.nunter- IF.n OpPr::ltion~l Integration Center (COIC)," COIC Response lO Efficiency Study satd that: DODIG-2014-05511 SIS€R~T...this information can be captured on open source. husiness lnrormation links and then converted into intelligeflce we can use lo Je ve ragt our...collect iutelligence, and was nol authorized lO collect intelligence on U.S. persons. (U/ /~)Furthermore, even if the intentional collecti on on U.S. pe

Task 90-17: Decontaminability Study on the U.S. Army Resuscitation Device, Individual, Chemical (RDIC)

DTIC Science & Technology

1991-04-01

RESTRIC-iVE VARK;NGS Unclassified 2a. SECURITY CLASSIF’CAT.ON AuTrHORITr 3 DISTRIBUTION,’AVALA8ILTY OF REPORT Approved for public release; 2b t ... T ;•R7 UTiON, AVAILABILITY OF ABSTRACT 121 A8STRACT SEC:RITY CLASSIFICATION (n UNCý.ASSiFE01IJNL,MITFD C3 SAME AS 7Pr 0 D:)rc usicts Unc la-,qi f it...was used to wipe the RDIC for 3 .i,,. The second, which is impregnated with chloramine B and is wetted with hydroxyethane (45 ± 2 percent), zinc

Summaries of Papers presented at the Picosecond Electronics and Optoelectronics Topical Meeting Held in Incline Village, Nevada on January 14-16, 1987. Conference Edition.

DTIC Science & Technology

1987-10-10

Invted Paper) Yen, Hughes Research Laboratories. Design and fabrica- FA1 Hgh-Spmd Phenomena In GaAs Quantum Wells, A. tion of wideband and high-speed...App!. Phys., 49 1119�). 5. A.M. Johnson, D.I. Auston, P.R. Smith, J.C. Dean, i.P. Harbison, and D. Kaplan ,r "Picosecond Photoconductivity in...JANUARY 16, 1987 PROSPECTOR! RUBICON ROOM 8:00 A.M.-9:30 A.M. FA1 -4 QUANTUM-WELL PHYSICS AND DEVICES C. Weisbuch, Thomson CSF, Presider .4

HIV Pre-Exposure Prophylaxis Stigma as a Multidimensional Barrier to Uptake Among Women Who Attend Planned Parenthood.

PubMed

Calabrese, Sarah K; Dovidio, John F; Tekeste, Mehrit; Taggart, Tamara; Galvao, Rachel W; Safon, Cara B; Willie, Tiara C; Caldwell, Abigail; Kaplan, Clair; Kershaw, Trace S

2018-05-22

PrEP uptake has lagged among US women. PrEP stigma is a recognized barrier to uptake among MSM but remains largely unexplored among women. This study examined the pervasiveness of PrEP stigma among US women and its implications for uptake. Setting/Methods: In a 2017 online survey of Planned Parenthood patients drawn from the three cities with the highest numbers of new HIV infections in Connecticut, 597 heterosexually-active, HIV-negative, PrEP-inexperienced women reported background characteristics, two dimensions of anticipated PrEP stigma (PrEP-user stereotypes and PrEP disapproval by others), and three indicators of potential PrEP uptake (interest in learning more about PrEP, intention to use PrEP, and comfort discussing PrEP with a provider). Participants commonly perceived PrEP-user stereotypes, with many believing that others would regard them as promiscuous (37%), HIV-positive (32%), bad (14%), or gay (11%) if they used PrEP. Thirty percent would feel ashamed to disclose PrEP use. Many participants expected disapproval by family (36%), sex partners (34%), and friends (25%). In adjusted analyses, perception of PrEP-user stereotypes was uniquely associated with lower comfort discussing PrEP with a provider. Expected PrEP disapproval by others was uniquely associated with less PrEP interest, less intention to use PrEP, and less comfort discussing PrEP with a provider. Exploratory moderation analyses suggested intention to use PrEP was greatest when participants anticipated low levels of both PrEP-user stereotypes and PrEP disapproval by others. Findings highlight the need for positive messaging targeting potential PrEP users and their social networks to increase PrEP acceptance and uptake.

Different structural stability and toxicity of PrP(ARR) and PrP(ARQ) sheep prion protein variants.

PubMed

Paludi, Domenico; Thellung, Stefano; Chiovitti, Katia; Corsaro, Alessandro; Villa, Valentina; Russo, Claudio; Ianieri, Adriana; Bertsch, Uwe; Kretzschmar, Hans A; Aceto, Antonio; Florio, Tullio

2007-12-01

The polymorphisms at amino acid residues 136, 154, and 171 in ovine prion protein (PrP) have been associated with different susceptibility to scrapie: animals expressing PrP(ARQ) [PrP(Ala136/Arg154/Gln171)] show vulnerability, whereas those that express PrP(ARR) [PrP(Ala136/Arg154/Arg171)] are resistant to scrapie. The aim of this study was to evaluate the in vitro toxic effects of PrP(ARR) and PrP(ARQ) variants in relation with their structural characteristics. We show that both peptides cause cell death inducing apoptosis but, unexpectedly, the scrapie resistant PrP(ARR) form was more toxic than the scrapie susceptible PrP(ARQ) variant. Moreover, the alpha-helical conformation of PrP(ARR) was less stable than that of PrP(ARQ) and the structural determinants responsible of these different conformational stabilities were characterized by spectroscopic analysis. We observed that PrP toxicity was inversely related to protein structural stability, being the unfolded conformation more toxic than the native one. However, the PrP(ARQ) variant displays a higher propensity to form large aggregates than PrP(ARR). Interestingly, in the presence of small amounts of PrP(ARR), PrP(ARQ) aggregability was reduced to levels similar to that of PrP(ARR). Thus, in contrast to PrP(ARR) toxicity, scrapie transmissibility seems to reside in the more stable conformation of PrP(ARQ) that allows the formation of large amyloid fibrils.

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

PubMed Central

Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants within the transmembrane region undergo an ER-stress mediated cell apoptosis. PMID:21298055

Scutellarin-graft cationic β-cyclodextrin-polyrotaxane: Synthesis, characterization and DNA condensation.

PubMed

Qin, Qi; Ma, Xue; Liao, Xiali; Yang, Bo

2017-02-01

As a prerequisite of gene delivery in living cells, DNA condensation has attracted more and more attention. In order to improve the efficiencies of polyamine-β-cyclodextrin-based cationic polyrotaxanes (PR-EDA and PR-DETA) as DNA condensation materials, we have designed and prepared two novel scutellarin-grafted cationic polyrotaxanes (PR-EDA-SCU and PR-DETA-SCU), in which scutellarins (SCU), the planar molecules, were conjugated on the cyclodextrin molecules of PR-EDA and PR-DETA. These materials were characterized by 1D and 2D NMR, XRD, TG and DSC. The electrophoresis assays showed that pDNA condensation efficiencies of PR-EDA and PR-DETA were better than that of PR-EDA and PR-DETA. The complexes of PR-EDA, PR-DETA, PR-EDA-SCU and PR-DETA-SCU with pDNA were further investigated by zeta potential and atomic force microscopy analysis. The results indicated that the planar structure of SCU played an important role in improvement of pDNA condensation efficiencies of PR-EDA-SCU and PR-DETA-SCU. The satisfactory pDNA condensation abilities of PR-EDA-SCU and PR-DETA-SCU could be helpful in designing non-viral gene delivery vectors to control gene expression and delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

PrP(C) homodimerization stimulates the production of PrPC cleaved fragments PrPN1 and PrPC1.

PubMed

Béland, Maxime; Motard, Julie; Barbarin, Alice; Roucou, Xavier

2012-09-19

An endoproteolytic cleavage termed α-cleavage between residues 111/112 is a characteristic feature of the cellular prion protein (PrP(C)). This cleavage generates a soluble N-terminal fragment (PrPN1) and a glycosylphosphatidylinositol-anchored C-terminal fragment (PrPC1). Independent studies demonstrate that modulating PrP(C) α-cleavage represents a potential therapeutic strategy in prion diseases. The regulation of PrP(C) α-cleavage is unclear. The only known domain that is essential for the α-cleavage to occur is a hydrophobic domain (HD). Importantly, the HD is also essential for the formation of PrP(C) homodimers. To explore the role of PrP(C) homodimerization on the α-cleavage, we used a well described inducible dimerization strategy whereby a chimeric PrP(C) composed of a modified FK506-binding protein (Fv) fused with PrP(C) and termed Fv-PrP is incubated in the presence of a dimerizer AP20187 ligand. We show that homodimerization leads to a considerable increase of PrP(C) α-cleavage in cultured cells and release of PrPN1 and PrPC1. Interestingly, enforced homodimerization increased PrP(C) levels at the plasma membrane, and preventing PrP(C) trafficking to the cell surface inhibited dimerization-induced α-cleavage. These observations were confirmed in primary hippocampal neurons from transgenic mice expressing Fv-PrP. The proteases responsible for the α-cleavage are still elusive, and in contrast to initial studies we confirm more recent investigations that neither ADAM10 nor ADAM17 are involved. Importantly, PrPN1 produced after PrP(C) homodimerization protects against toxic amyloid-β (Aβ) oligomers. Thus, our results show that PrP(C) homodimerization is an important regulator of PrP(C) α-cleavage and may represent a potential therapeutic avenue against Aβ toxicity in Alzheimer's disease.

Progesterone Receptor-A and -B Have Opposite Effects on Proinflammatory Gene Expression in Human Myometrial Cells: Implications for Progesterone Actions in Human Pregnancy and Parturition

PubMed Central

Tan, Huiqing; Yi, Lijuan; Rote, Neal S.; Hurd, William W.

2012-01-01

Context: Progesterone promotes uterine relaxation during pregnancy and its withdrawal induces labor. Progesterone withdrawal in human parturition is mediated in part by changes in the relative levels of the nuclear progesterone receptor isoforms, PR-A and PR-B, in myometrial cells. Parturition also involves myometrial inflammation; however, the functional link between nuclear PR-mediated progesterone actions and inflammation in human myometrial cells is unclear. Objective: Our objective was to determine how PR-A and PR-B regulate progesterone action in human myometrial cells and specifically the expression of genes encoding contraction-associated proteins and proinflammatory mediators. Design: Effects of PR-A and PR-B on the capacity for progesterone to modulate gene expression was determined using an immortalized human myometrial cell line stably transfected with inducible PR-A and PR-B expression transgenes and conditioned to express various PR-A and PR-B levels. Gene expression was assessed by genome wide transcriptome analysis, quantitative RT-PCR and immunoblotting. Results: PR-A and PR-B were each transcriptionally active in response to progesterone and affected the expression of distinct gene cohorts. The capacity for progesterone to affect gene expression was dependent on the PR-A to PR-B ratio. This was especially apparent for the expression of proinflammatory genes. Progesterone decreased proinflammatory gene expression when the PR-A to PR-B ratio favored PR-B and increased proinflammatory gene expression when the ratio favored PR-A. Progesterone via PR-B increased expression of inhibitor-κBα, a repressor of the nuclear factor-κB transcription factor, and inhibited basal and lipopolysaccharide-induced proinflammatory gene expression. Both of those PR-B-mediated effects were inhibited by PR-A. Conclusions: Our data suggest that during most of human pregnancy, when myometrial cells are PR-B dominant, progesterone promotes myometrial quiescence through PR-B-mediated antiinflammatory actions. At parturition, the rise in PR-A expression promotes labor by inhibiting the antiinflammatory actions of PR-B and stimulating proinflammatory gene expression in response to progesterone. PMID:22419721

20 CFR Appendix A to Subpart F of... - U.S. Seaports

Code of Federal Regulations, 2013 CFR

2013-04-01

... Guanica, PR Guayanilla, PR Humacao, PR Jobos, PR Mayaguez, PR Ponce, PR San Juan, PR Vieques, PR Yabucoa... Port Costa, CA Port Hueneme, CA Port San Luis, CA Redwood City, CA Richmond, CA Sacramento, CA San Diego, CA San Francisco, CA Selby, CA Stockton, CA Vallejo, CA Ventura, CA Barbers Point, HI Hilo, HI...

20 CFR Appendix A to Subpart F of... - U.S. Seaports

Code of Federal Regulations, 2011 CFR

2011-04-01

... Guanica, PR Guayanilla, PR Humacao, PR Jobos, PR Mayaguez, PR Ponce, PR San Juan, PR Vieques, PR Yabucoa... Port Costa, CA Port Hueneme, CA Port San Luis, CA Redwood City, CA Richmond, CA Sacramento, CA San Diego, CA San Francisco, CA Selby, CA Stockton, CA Vallejo, CA Ventura, CA Barbers Point, HI Hilo, HI...

20 CFR Appendix A to Subpart F of... - U.S. Seaports

Code of Federal Regulations, 2012 CFR

2012-04-01

... Guanica, PR Guayanilla, PR Humacao, PR Jobos, PR Mayaguez, PR Ponce, PR San Juan, PR Vieques, PR Yabucoa... Port Costa, CA Port Hueneme, CA Port San Luis, CA Redwood City, CA Richmond, CA Sacramento, CA San Diego, CA San Francisco, CA Selby, CA Stockton, CA Vallejo, CA Ventura, CA Barbers Point, HI Hilo, HI...

20 CFR Appendix A to Subpart F of... - U.S. Seaports

Code of Federal Regulations, 2014 CFR

2014-04-01

... Guanica, PR Guayanilla, PR Humacao, PR Jobos, PR Mayaguez, PR Ponce, PR San Juan, PR Vieques, PR Yabucoa... Port Costa, CA Port Hueneme, CA Port San Luis, CA Redwood City, CA Richmond, CA Sacramento, CA San Diego, CA San Francisco, CA Selby, CA Stockton, CA Vallejo, CA Ventura, CA Barbers Point, HI Hilo, HI...

Effects of Intrauterine Devices in Mares: A Histomorphological and Immunohistochemical Evaluation of the Endometrium.

PubMed

Klein, V; Müller, K; Schoon, H A; Reilas, T; Rivera del Alamo, M M; Katila, T

2016-02-01

Oestrous suppression by intrauterine devices (IUDs) is caused by prolongation of luteal function, but the biological mechanism is unknown. The aim of the study was to investigate mechanisms which could explain the action of IUDs. Thirty mares were age-matched and either inseminated (AI, n = 15) or fitted with an IUD (IUD, n = 15) and subsequently divided into four groups: AI-P, pregnant (n = 8); AI-N, non-pregnant (n = 7); IUD-P, prolonged luteal phase (n = 7); and IUD-N, normal luteal phase (n = 8). The median ages were 5.5 and 7 years in AI-P and IUD-P groups and 14 and 11 years in AI-N and IUD-N groups, respectively. On Day 15 after ovulation, an endometrial biopsy was obtained to study histomorphological and immunohistochemical expression patterns of uterine proteins (uteroferrin, UF; uterocalin, UC; uteroglobin, UG), oestrogen and progesterone receptors (ER, PR), proliferation marker Ki-67 and content of inflammatory cells. Expression of UF was higher in IUD mares; the difference between pregnant and IUD-P mares was significant. Mares exhibiting a prolonged luteal phase (AI-P, IUD-P) showed only mild angiosclerosis and lower expression of both ER and PR than mares with a normal luteal phase (AI-N, IUD-N). No significant differences were detected in the numbers of inflammatory cells, with the exception of macrophages, which were more numerous in AI-P than AI-N mares. Although inflammatory cells were not detected in IUD mares, increased UF levels may indicate chronic inflammation. Young age and normality of the endometrial blood vessels may improve the efficacy of IUDs. © 2015 Blackwell Verlag GmbH.

A sipometer for measuring motivation to consume and reward value of foods and beverages in humans: Description and proof of principle.

PubMed

Hogenkamp, P S; Shechter, A; St-Onge, M-P; Sclafani, A; Kissileff, H R

2017-03-15

New methods, derived from animal work, for measuring food reward value (i.e. reinforcing value of food), and motivation (i.e. strength of desire) to consume, in humans are described and validated. A sipping device (sipometer) was developed that permits access to a liquid food or beverage on two reward schedules: continuous reinforcement (CR) and progressively increasing time spent exerting pressure on a straw (PR-schedule). In addition, a pictorial scale showing a cup, from which the 'amount wanted' could be marked was used to pre-test potential consumption. Intake, time spent sipping, breakpoint, and pressure exerted were the main dependent variables measured. Three pilot experiments were conducted. In Experiment 1, participants (n=8) consumed yogurt shakes after a 1-h or 21-h food deprivation period on both schedules. In Experiment 2, participants (n=8) sham-consumed (i.e. spit out) sweet and non-sweet beverages, utilizing both schedules. In Experiment 3, sham-consuming sweet and non-sweet beverages on both schedules and working for shake on the PR schedule were repeated, after three nights of either habitual sleep or short sleep duration (n=7) in a crossover design. In Experiment 1, participants sipped longer after 21-h vs. 1-h of food deprivation (13±3.0 vs. 8.0±2.1s; p=0.04), on the PR schedule. In Experiment 2, sham-intake (p=0.01) and sipping time (p=0.04) were greater for sweet than non-sweet beverages on the PR schedule and a similar, though not conventionally significant, effect was observed for exerted pressure (p=0.09). In both Experiment 2 and Experiment 3 after habitual sleep, on the PR schedule, cumulative pressure difference between sweet and non-sweet beverage increased with difference in amount wanted in the taste test. In contrast, after short sleep participants were less willing to work for sweet taste as their wanting increased, suggesting that sleep deprivation raises desire, but lowers behavioral output. Taken together these results demonstrate that the sipometer and associated ratings are reliable and useful measures of motivation to consume and reward value in humans. Participants were more motivated to obtain access to sweet beverages, especially when these were better liked than to obtain access to non-sweet beverages. Copyright © 2017 Elsevier Inc. All rights reserved.

A sipometer for measuring motivation to consume and reward value of foods and beverages in humans: Description and proof of principle

PubMed Central

Hogenkamp, PS; Shechter, A.; St-Onge, M-P; Sclafani, A; Kissileff, HR

2017-01-01

New methods, derived from animal work, for measuring food reward value (i.e. reinforcing value of food), and motivation (i.e. strength of desire) to consume, in humans are described and validated. A sipping device (sipometer) was developed that permits access to a liquid food or beverage on two reward schedules: continuous reinforcement (CR) and progressively increasing time spent exerting pressure on a straw (PR-schedule). In addition, a pictorial scale showing a cup, from which the ‘amount wanted’ could be marked was used to pre-test potential consumption. Intake, time spent sipping, breakpoint, and pressure exerted were the main dependent variables measured. Three pilot experiments were conducted. In Experiment 1, participants (n = 8) consumed yogurt shakes after a 1-h or 21-h food deprivation period on both schedules. In Experiment 2, participants (n = 8) sham-consumed (i.e. spit out) sweet and non-sweet beverages, utilizing both schedules. In Experiment 3, sham-consuming sweet and non-sweet beverages on both schedules and working for shake on the PR schedule were repeated, after three nights of either habitual sleep or short sleep duration (n = 7) in a crossover design. In Experiment 1, participants sipped longer after 21-h vs. 1-h of food deprivation (13 ± 3.0 vs. 8.0 ± 2.1 s; p = 0.04), on the PR schedule. In Experiment 2, sham-intake (p = 0.01) and sipping time (p = 0.04) were greater for sweet than non-sweet beverages on the PR schedule and a similar, though not conventionally significant, effect was observed for exerted pressure (p = 0.09). In both Experiment 2 and Experiment 3 after habitual sleep, on the PR schedule, cumulative pressure difference between sweet and non-sweet beverage increased with difference in amount wanted in the taste test. In contrast, after short sleep participants were less willing to work for sweet taste as their wanting increased, suggesting that sleep deprivation raises desire, but lowers behavioral output. Taken together these results demonstrate that the sipometer and associated ratings are reliable and useful measures of motivation to consume and reward value in humans. Participants were more motivated to obtain access to sweet beverages, especially when these were better liked than to obtain access to non-sweet beverages. PMID:28089706

Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases.

PubMed

Triki, Dhoha; Billot, Telli; Visseaux, Benoit; Descamps, Diane; Flatters, Delphine; Camproux, Anne-Claude; Regad, Leslie

2018-04-10

HIV-2 protease (PR2) is naturally resistant to most FDA (Food and Drug Administration)-approved HIV-1 protease inhibitors (PIs), a major antiretroviral class. In this study, we compared the PR1 and PR2 binding pockets extracted from structures complexed with 12 ligands. The comparison of PR1 and PR2 pocket properties showed that bound PR2 pockets were more hydrophobic with more oxygen atoms and fewer nitrogen atoms than PR1 pockets. The structural comparison of PR1 and PR2 pockets highlighted structural changes induced by their sequence variations and that were consistent with these property changes. Specifically, substitutions at residues 31, 46, and 82 induced structural changes in their main-chain atoms that could affect PI binding in PR2. In addition, the modelling of PR1 mutant structures containing V32I and L76M substitutions revealed a cooperative mechanism leading to structural deformation of flap-residue 45 that could modify PR2 flexibility. Our results suggest that substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which could underlie PR2 resistance against PIs. These results provide new insights concerning the structural changes induced by PR1 and PR2 pocket variation changes, improving the understanding of the atomic mechanism of PR2 resistance to PIs.

Launcher Dynamic Data Acquisition

DTIC Science & Technology

2012-07-31

K PR Pressure PR Pressure PR Accelerometer PR Accelerometer PR Accelerometer PR Pressure PR Pressure IEPE Microphone IEPE ...transducers, displacement potentiometers, or Integrated Electronics Piezoelectric ( IEPE ) microphones and accelerometers. The characteristics of these...Engineering Units HCl hydrogen chloride HVAC heating ventilation and cooling Hz hertz IEC International Electrotechnical Commission IEPE

Home-based pre-exposure prophylaxis (PrEP) services for gay and bisexual men: An opportunity to address barriers to PrEP uptake and persistence

PubMed Central

Rendina, H. Jonathon; Grov, Christian

2017-01-01

Gay, bisexual, and other men who have sex with men (GBM) are disproportionately affected by the HIV epidemic. Despite the promise of pre-exposure prophylaxis (PrEP) in reducing HIV transmission risk, barriers for uptake and persistence exist. We sought to identify whether GBM in a nationwide cohort who have not yet initiated PrEP (n = 906) would prefer to get PrEP-related care from a primary care provider (PCP) compared to a specialist clinic or provider. We then sought to identify their level of interest and factors associated with preference for using home-based PrEP services (i.e., HB-PrEP), defined to participants as conducting HIV/STI self-testing from home with PrEP prescription mailing after an initial in-person clinic visit. We examined the associations of demographics, sexual HIV transmission risk, concern about frequent medical checkups associated with PrEP, health care access, and PrEP intentions with preferences for healthcare provider type and HB-PrEP. Concern about frequent medical checkups were associated with preferring a PCP for PrEP-related care, but men who perceived a barrier to bringing up the topic of PrEP with a doctor preferred a specialist clinic or provider more than a PCP. HB-PrEP was more appealing for younger men and those engaged in sexual HIV transmission risk, suggesting HB-PrEP could help reach GBM most vulnerable to HIV and in need of PrEP. HB-PrEP expansion has potential to increase PrEP uptake and persistence among GBM, particularly for men with barriers to clinic-based care and higher intentions to initiate PrEP. Clinical guidelines regarding HB-PrEP are needed to expand its use. PMID:29281688

The synthesis of PNP-supported low-spin nitro manganese(I) carbonyl complexes

DOE PAGES

Tondreau, Aaron M.; Boncella, James M.

2016-09-01

In this study, the coordination chemistry of Mn(CO) 5Br was investigated with a series of PNP-pincer ligands. The ligands iPrPONOP ( iPrPONOP = 2,6-bis(diisopropylphosphinito)pyridine) and iPrPN HP ( iPrPN HP = HN{CH 2CH 2(PiPr 2)} 2) gave the desired organometallic manganese complexes ( iPrPONOP)Mn(CO) 2Br and ( iPrPN HP)Mn(CO) 2Br, respectively, upon chelation to Mn(CO) 5Br. The reactivity of iPrPNNNP ( iPrPNNNP = N,N'-bis(diisopropylphosphino)-2,6-diaminopyridine) with Mn(CO) 5Br yielded a pair of products, [( iPrPNNNP)Mn(CO) 3][Br] and ( iPrPNNNCO)Mn(CO) 3. The formation of the asymmetric chelate arises from a formal loss of iPr 2PBr and C–N bond formation from a carbonylmore » ligand and NH, yielding a Mn(I) amide core. The nitration reactions of ( iPrPONOP)Mn(CO) 2Br and ( iPrPN HP)Mn(CO) 2Br were carried out using silver nitrite, yielding the nitro compounds ( iPrPONOP)Mn(CO) 2(NO 2) and ( iPrPN HP)Mn(CO) 2(NO 2), respectively. The analogous iron complex ( iPrPONOP)Fe(CO)Cl 2 was nitrated under the same conditions to yield the salt pair [( iPrPONOP)Fe(CO) 2][FeCl 3NO]. This reactivity underlines the difference between iso-valent iron and manganese centers. The manganese complexes ( iPrPONOP)Mn(CO) 2(NO 2) and ( iPrPN HP)Mn(CO) 2(NO 2) were ineffective as oxygen atom transfer reagents for a variety of substrates.« less

Factors affecting publication in peer-reviewed journals of abstracts presented from 2008 to 2012 ACVO meetings.

PubMed

Bentley, Ellison; Koester, Megan; Bdolah-Abram, Tali; Yair, Nadav; Ofri, Ron

2018-04-14

To examine variables that affect publication of ACVO meeting abstracts in peer-reviewed journals and compare results to ECVO publication rate (PR). Published papers were identified via online searches for abstracts from 2008 to 2012 ACVO/ECVO meetings. Variables analyzed (via Pearson's chi-Squared test) included the following: oral presentation/poster, type of abstract (clinical/basic science/case report), species, ocular tissue, nationality, funding, first/last/any author a diplomate, resident as first author, and author affiliation (private practice/university). One hundred and eighty-six of 577 ACVO abstracts were published within 608 ± 479 days, with 103 published in Veterinary Ophthalmology. Significant factors included the following: nationality of first/last authors (P = .005); English as first language (P < .001); presentation type (P < .001, oral 40% PR, poster 22% PR); type of study (P = .037, clinical study 35% PR, basic science 30% PR, case report 16% PR); resident as first author (P < .001); diplomate as any author except first/last (P < .001); first author affiliation (P = .001, university 37% PR, practice 21% PR); last author affiliation (P = .003, university 36% PR, practice 22% PR); and species (P < .001, horses 53% PR, multiple species 50% PR, cats 35% PR, food animals 31% PR, exotics/wildlife 31% PR, dogs 27% PR, laboratory animals/in vitro 24%). Nonsignificant factors were as follows: diplomate as first/last author, funding, and ocular tissue. Presentation type, resident as first author, university affiliation of first author, and species had the greatest effect on publication probability. For the same period, ECVO PR was 87 of 299, which was not significantly different from ACVO PR (P = .342). At 32%, ACVO PR for the study years is similar to ECVO PR of 29%. © 2018 American College of Veterinary Ophthalmologists.

Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains

PubMed Central

Vey, Martin; Pilkuhn, Susanne; Wille, Holger; Nixon, Randal; DeArmond, Stephen J.; Smart, Eric J.; Anderson, Richard G. W.; Taraboulos, Albert; Prusiner, Stanley B.

1996-01-01

Results of transgenetic studies argue that the scrapie isoform of the prion protein (PrPSc) interacts with the substrate cellular PrP (PrPC) during conversion into nascent PrPSc. While PrPSc appears to accumulate primarily in lysosomes, caveolae-like domains (CLDs) have been suggested to be the site where PrPC is converted into PrPSc. We report herein that CLDs isolated from scrapie-infected neuroblastoma (ScN2a) cells contain PrPC and PrPSc. After lysis of ScN2a cells in ice-cold Triton X-100, both PrP isoforms and an N-terminally truncated form of PrPC (PrPC-II) were found concentrated in detergent-insoluble complexes resembling CLDs that were isolated by flotation in sucrose gradients. Similar results were obtained when CLDs were purified from plasma membranes by sonication and gradient centrifugation; with this procedure no detergents are used, which minimizes artifacts that might arise from redistribution of proteins among subcellular fractions. The caveolar markers ganglioside GM1 and H-ras were found concentrated in the CLD fractions. When plasma membrane proteins were labeled with the impermeant reagent sulfo-N-hydroxysuccinimide-biotin, both PrPC and PrPSc were found biotinylated in CLD fractions. Similar results on the colocalization of PrPC and PrPSc were obtained when CLDs were isolated from Syrian hamster brains. Our findings demonstrate that both PrPC and PrPSc are present in CLDs and, thus, support the hypothesis that the PrPSc formation occurs within this subcellular compartment. PMID:8962161

Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice.

PubMed

Hara, Hideyuki; Miyata, Hironori; Das, Nandita Rani; Chida, Junji; Yoshimochi, Tatenobu; Uchiyama, Keiji; Watanabe, Hitomi; Kondoh, Gen; Yokoyama, Takashi; Sakaguchi, Suehiro

2018-01-01

Conformational conversion of the cellular isoform of prion protein, PrP C , into the abnormally folded, amyloidogenic isoform, PrP Sc , is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrP C into PrP Sc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/ Prnp 0 / 0 mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrP Sc ΔOR in their brains. We show here that Tg(PrPΔOR)/ Prnp 0 / 0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrP Sc ΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrP C into PrP Sc after infection with BSE prions. However, Tg(PrPΔOR)/ Prnp 0 / 0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrP Sc ΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/ Prnp 0 / 0 mice than PrP Sc in control wild-type mice. Taken together, these results indicate that the OR region of PrP C could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. IMPORTANCE Structure-function relationship studies of PrP C conformational conversion into PrP Sc are worthwhile to understand the mechanism of the conversion of PrP C into PrP Sc We show here that, by inoculating Tg(PrPΔOR)/ Prnp 0 / 0 mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrP C into PrP Sc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrP Sc ΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrP Sc ΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrP C into PrP Sc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions. Copyright © 2017 American Society for Microbiology.

Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3.

PubMed

Heaslet, Holly; Lin, Ying-Chuan; Tam, Karen; Torbett, Bruce E; Elder, John H; Stout, C David

2007-01-09

We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants 1234. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively 234. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heaslet, H.; Lin, Y.-C.; Tam, K.

We have obtained the 1.7 angstrom crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants [1-4]. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectivelymore » [2-4]. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed the formation of additional van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR.« less

Novel receptor-like kinases in cacao contain PR-1 extracellular domains.

PubMed

Teixeira, Paulo José Pereira Lima; Costa, Gustavo Gilson Lacerda; Fiorin, Gabriel Lorencini; Pereira, Gonçalo Amarante Guimarães; Mondego, Jorge Maurício Costa

2013-08-01

Members of the pathogenesis-related protein 1 (PR-1) family are well-known markers of plant defence responses, forming part of the arsenal of the secreted proteins produced on pathogen recognition. Here, we report the identification of two cacao (Theobroma cacao L.) PR-1s that are fused to transmembrane regions and serine/threonine kinase domains, in a manner characteristic of receptor-like kinases (RLKs). These proteins (TcPR-1f and TcPR-1g) were named PR-1 receptor kinases (PR-1RKs). Phylogenetic analysis of RLKs and PR-1 proteins from cacao indicated that PR-1RKs originated from a fusion between sequences encoding PR-1 and the kinase domain of a LecRLK (Lectin Receptor-Like Kinase). Retrotransposition marks surround TcPR-1f, suggesting that retrotransposition was involved in the origin of PR-1RKs. Genes with a similar domain architecture to cacao PR-1RKs were found in rice (Oryza sativa), barrel medic (Medicago truncatula) and a nonphototrophic bacterium (Herpetosiphon aurantiacus). However, their kinase domains differed from those found in LecRLKs, indicating the occurrence of convergent evolution. TcPR-1g expression was up-regulated in the biotrophic stage of witches' broom disease, suggesting a role for PR-1RKs during cacao defence responses. We hypothesize that PR-1RKs transduce a defence signal by interacting with a PR-1 ligand. © 2013 BSPP AND JOHN WILEY & SONS LTD.

Phylogenetic analysis of PR genes in some pome fruit species with the emphasis on transcriptional analysis and ROS response under Erwinia amylovora inoculation in apple.

PubMed

Hassani, Maryam; Salami, Seyed Alireza; Nasiri, Jaber; Abdollahi, Hamid; Ghahremani, Zahra

2016-02-01

Attempts were made to identify eight pathogenesis related (PR) genes (i.e., PR-1a, PR3-ch1, PR3-Ch2, PR3-Ch3, PR3-Ch4, PR3-Ch5, PR-5 and PR-8) from 27 genotypes of apple, quince and pear, which are induced in response to inoculation with the pathogen Erwinia amylovora, the causal agent of fire blight. Totally, 32 PR genes of different families were obtained, excepting PR3-Ch2 (amplified only in apple) and PR3-Ch4 (amplified only in apple and pear), the others were successfully amplified in all the genotypes of apple, quince and pear. Evolutionary, the genes of each family exhibited significant homology with each other, as the corresponded phylogenetic neighbor-joining-based dendrograms were taken into consideration. Meanwhile, according to the expression assay, it was deduced that the pathogen activity can significantly affect the expression levels of some selected PR genes of PR3-Ch2, PR3-Ch4, PR3-Ch5 and particularly Cat I in both resistant (MM-111) and semi-susceptible (MM-106) apple rootstocks. Lastly, it was concluded that the pathogen E. amylovora is able to stimulate ROS response, particularly using generation of hydrogen peroxide (H2O2) in both aforementioned apple rootstock.

An overview of Experimental Condensed Matter Physics in Argentina by 2014, and Oxides for Non Volatile Memory Devices: The MeMOSat Project

NASA Astrophysics Data System (ADS)

Levy, Pablo

2015-03-01

In the first part of my talk, I will describe the status of the experimental research in Condensed Matter Physics in Argentina, biased towards developments related to micro and nanotechnology. In the second part, I will describe the MeMOSat Project, a consortium aimed at producing non-volatile memory devices to work in aggressive environments, like those found in the aerospace and nuclear industries. Our devices rely on the Resistive Switching mechanism, which produces a permanent but reversible change in the electrical resistance across a metal-insulator-metal structure by means of a pulsed protocol of electrical stimuli. Our project is devoted to the study of Memory Mechanisms in Oxides (MeMO) in order to establish a technological platform that tests the Resistive RAM (ReRAM) technology for aerospace applications. A review of MeMOSat's activities is presented, covering the initial Proof of Concept in ceramic millimeter sized samples; the study of different oxide-metal couples including (LaPr)2/3Ca1/3MnO, La2/3Ca1/3MnO3, YBa2Cu3O7, TiO2, HfO2, MgO and CuO; and recent miniaturized arrays of micrometer sized devices controlled by in-house designed electronics, which were launched with the BugSat01 satellite in June2014 by the argentinian company Satellogic.

Recombinant human prion protein inhibits prion propagation in vitro.

PubMed

Yuan, Jue; Zhan, Yi-An; Abskharon, Romany; Xiao, Xiangzhu; Martinez, Manuel Camacho; Zhou, Xiaochen; Kneale, Geoff; Mikol, Jacqueline; Lehmann, Sylvain; Surewicz, Witold K; Castilla, Joaquín; Steyaert, Jan; Zhang, Shulin; Kong, Qingzhong; Petersen, Robert B; Wohlkonig, Alexandre; Zou, Wen-Quan

2013-10-09

Prion diseases are associated with the conformational conversion of the cellular prion protein (PrP(C)) into the pathological scrapie isoform (PrP(Sc)) in the brain. Both the in vivo and in vitro conversion of PrP(C) into PrP(Sc) is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrP(Sc), but not PrP(C), suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrP(C) with PrP(Sc). Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrP(Sc) propagation without inducing immune response side effects.

Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification

PubMed Central

Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

2016-01-01

Prions are formed of misfolded assemblies (PrPSc) of the variably N-glycosylated cellular prion protein (PrPC). In infected species, prions replicate by seeding the conversion and polymerization of host PrPC. Distinct prion strains can be recognized, exhibiting defined PrPSc biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrPSc assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrPC glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrPC species of interest as substrate. Applying the technique to PrPC glycosylation mutants expressing cells revealed that neither PrPC nor PrPSc glycoform stoichiometry was instrumental to PrPSc formation and strainness perpetuation. Our study supports the view that strain properties, including PrPSc glycotype are enciphered within PrPSc structural backbone, not in the attached glycans. PMID:27384922

Prions amplify through degradation of the VPS10P sorting receptor sortilin.

PubMed

Uchiyama, Keiji; Tomita, Mitsuru; Yano, Masashi; Chida, Junji; Hara, Hideyuki; Das, Nandita Rani; Nykjaer, Anders; Sakaguchi, Suehiro

2017-06-01

Prion diseases are a group of fatal neurodegenerative disorders caused by prions, which consist mainly of the abnormally folded isoform of prion protein, PrPSc. A pivotal pathogenic event in prion disease is progressive accumulation of prions, or PrPSc, in brains through constitutive conformational conversion of the cellular prion protein, PrPC, into PrPSc. However, the cellular mechanism by which PrPSc is progressively accumulated in prion-infected neurons remains unknown. Here, we show that PrPSc is progressively accumulated in prion-infected cells through degradation of the VPS10P sorting receptor sortilin. We first show that sortilin interacts with PrPC and PrPSc and sorts them to lysosomes for degradation. Consistently, sortilin-knockdown increased PrPSc accumulation in prion-infected cells. In contrast, overexpression of sortilin reduced PrPSc accumulation in prion-infected cells. These results indicate that sortilin negatively regulates PrPSc accumulation in prion-infected cells. The negative role of sortilin in PrPSc accumulation was further confirmed in sortilin-knockout mice infected with prions. The infected mice had accelerated prion disease with early accumulation of PrPSc in their brains. Interestingly, sortilin was reduced in prion-infected cells and mouse brains. Treatment of prion-infected cells with lysosomal inhibitors, but not proteasomal inhibitors, increased the levels of sortilin. Moreover, sortilin was reduced following PrPSc becoming detectable in cells after infection with prions. These results indicate that PrPSc accumulation stimulates sortilin degradation in lysosomes. Taken together, these results show that PrPSc accumulation of itself could impair the sortilin-mediated sorting of PrPC and PrPSc to lysosomes for degradation by stimulating lysosomal degradation of sortilin, eventually leading to progressive accumulation of PrPSc in prion-infected cells.

Adolescent Human Immunodeficiency Virus Care Providers’ Attitudes Toward the Use of Oral Pre-Exposure Prophylaxis in Youth

PubMed Central

Zimet, Gregory; Lally, Michelle; Kahn, Jessica A.

2016-01-01

Abstract Oral pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention is currently indicated for use in adults in the United States and may soon be indicated for minor adolescents. However, implementation of PrEP use among minors may present unique barriers. We conducted 15 individual, semi-structured interviews among US clinicians caring for HIV-infected and at-risk youth. The theory-driven interview guide assessed demographics, perceived role of oral PrEP in HIV prevention among adolescents, perceived barriers to and facilitating factors for use of PrEP in adolescents, and clinician-reported likelihood of prescribing PrEP. Transcripts were analyzed using framework analysis. Overall, clinicians viewed PrEP as a time-limited intervention that is one part of a comprehensive approach to HIV prevention among adolescents. Perceived barriers to prescribing to minors included concerns about: confidentiality, legality of minors consenting to PrEP without parental involvement, ability of minors to understand the risks/benefits of PrEP, the possible impact of PrEP on bone accrual, off-label use of PrEP medication in minors, and the high costs associated with PrEP use. Clinician-reported facilitating factors for prescribing PrEP to youth included educating communities and other clinicians about PrEP, ensuring adequate financial resources and infrastructure for delivering PrEP, developing formal guidance on effective behavioral interventions that should be delivered with PrEP, and gaining personal experience with prescribing PrEP. Clinicians indicated greater comfort with prescribing PrEP to adults versus minors. For PrEP to become more widely available to youth at risk for HIV infection, barriers that are unique to PrEP use in minors must be addressed. PMID:27410497

“Support Your Client at the Space That They're in”: HIV Pre-Exposure Prophylaxis (PrEP) Prescribers' Perspectives on PrEP-Related Risk Compensation

PubMed Central

Magnus, Manya; Mayer, Kenneth H.; Krakower, Douglas S.; Eldahan, Adam I.; Hawkins, Lauren A. Gaston; Underhill, Kristen; Hansen, Nathan B.; Kershaw, Trace S.; Betancourt, Joseph R.; Dovidio, John F.

2017-01-01

Abstract Despite the demonstrated effectiveness of HIV pre-exposure prophylaxis (PrEP) and evidence that most PrEP users do not engage in risk compensation (i.e., increased risk behavior due to a perceived decrease in HIV susceptibility), some healthcare providers report patient risk compensation to be a deterrent to prescribing PrEP. Overcoming this barrier is essential to supporting PrEP access and uptake among people at risk for HIV. To inform such efforts, this qualitative study explored PrEP-related risk compensation attitudes among providers with firsthand experience prescribing PrEP. US-based PrEP providers (n = 18), most of whom were HIV specialists, were recruited through direct outreach and referral from colleagues and other participants. Individual 90-min semistructured interviews were conducted by phone or in person from September 2014 through February 2015, transcribed, and thematically analyzed. Three attitudinal themes emerged: (1) providers' role is to support patients in making informed decisions, (2) risk behavior while taking PrEP does not fully offset PrEP's protective benefit (i.e., PrEP confers net protection, even with added behavioral risk), and (3) PrEP-related risk compensation is unduly stigmatized within and beyond the healthcare community. Participants were critical of other healthcare providers' negative judgment of patients and reluctance to prescribe PrEP due to anticipated risk compensation. Several providers also acknowledged an evolution in their thinking from initial ambivalence toward greater acceptance of PrEP and PrEP-related behavior change. PrEP providers' insights about risk compensation may help to address unsubstantiated concerns about PrEP-related risk compensation and challenge the acceptability of withholding PrEP on these grounds. PMID:28414261

Active FOXO1 is a Key Determinant of Isoform-Specific Progesterone Receptor Transactivation and Senescence Programming

PubMed Central

Diep, Caroline H.; Knutson, Todd P.; Lange, Carol A.

2015-01-01

Progesterone promotes differentiation coupled to proliferation and pro-survival in the breast, but inhibits estrogen-driven growth in the reproductive tract and ovaries. Herein, it is demonstrated, using progesterone receptor (PR) isoform-specific ovarian cancer model systems, that PR-A and PR-B promote distinct gene expression profiles that differ from PR-driven genes in breast cancer cells. In ovarian cancer models, PR-A primarily regulates genes independently of progestin, while PR-B is the dominant ligand-dependent isoform. Notably, FOXO1 and the PR/FOXO1 target-gene p21 (CDKN1A) are repressed by PR-A, but induced by PR-B. In the presence of progestin, PR-B, but not PR-A, robustly induced cellular senescence via FOXO1-dependent induction of p21 and p15 (CDKN2B). Chromatin immunoprecipitation (ChIP) assays performed on PR-isoform specific cells demonstrated that while each isoform is recruited to the same PRE-containing region of the p21 promoter in response to progestin, only PR-B elicits active chromatin marks. Overexpression of constitutively active FOXO1 in PR-A-expressing cells conferred robust ligand-dependent upregulation of the PR-B target genes GZMA, IGFBP1, and p21, and induced cellular senescence. In the presence of endogenous active FOXO1, PR-A was phosphorylated on Ser294 and transactivated PR-B at PR-B target genes; these events were blocked by the FOXO1 inhibitor (AS1842856). PR isoform-specific regulation of the FOXO1/p21 axis recapitulated in human primary ovarian tumor explants treated with progestin; loss of progestin sensitivity correlated with high AKT activity. PMID:26577046

Investigation of multiferroic behavior on flakes-like BiFeO{sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheikh, Javed R.; Gaikwad, Vishwajit M.; Acharya, Smita A., E-mail: saha275@yahoo.com

2016-05-23

In present work, multiferroic BiFeO{sub 3} was synthesized by hydrothermal route. The rhombohedral structure was confirmed X-ray diffraction pattern and data fitted with Reitveld refinement using Full-Prof software suite. SEM micrograph shows flake like morphology. Frequency and temperature dependence of dielectric constant and dielectric loss were studied and detected enhancement in dielectric constant. The magnetic measurement indicates antiferromagnetic nature of BFO. P-E curve shows ferroelectic hysteresis loop with remanent polarization (2Pr) 0.3518 µC/cm{sup 2}. The dielectric anomaly observed near T{sub N} can be assigned to magnetoelectric coupling which is useful in device application.

Progesterone receptor isoforms in the mammary gland of cats and dogs.

PubMed

Gracanin, A; de Gier, J; Zegers, K; Bominaar, M; Rutteman, G R; Schaefers-Okkens, A C; Kooistra, H S; Mol, J A

2012-12-01

Progesterone exerts its effect by binding to specific progesterone receptors (PR) within the cell. In dogs and cats, no data are available on PR isoforms as found in other species. We therefore investigated the sequence of the PR gene and encoded protein in dogs and cats, the expression of PR isoforms in mammary tissue using Western blots and the presence of PR in mammary tissue using immunohistochemistry. Comparison of the amino acid sequence of the canine and feline PR with human PR revealed major differences in the PR-B-specific upstream segment (BUS). However, the essential activation function 3 (AF3) domain was intact in the cat but mutated in the dog. The DNA and ligand-binding domains were highly similar among the species. In cats with fibroadenomatous hyperplasia (FAH), high expression of PR mRNA together with growth hormone (GH), GH receptor (GHR) and IGF-I mRNA was found in comparison with feline mammary carcinomas. Immunohistochemical analysis showed strong nuclear as well as cytoplasmic staining for PR in FAH. Western blot analysis revealed expression of the PR-A and PR-B isoforms in the feline mammary gland. In canine mammary tissue, the most abundant PR staining was found in proliferative zones of the mammary gland. Western blot analyses showed mainly staining for PR-A with lower PR-B staining. It is concluded that in dogs and cats both PR isoforms are expressed. The role of mutations found in the canine PR-B is discussed. © 2012 Blackwell Verlag GmbH.

Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based inhibitor, TL-3

PubMed Central

Heaslet, Holly; Lin, Ying-Chuan; Tam, Karen; Torbett, Bruce E; Elder, John H; Stout, C David

2007-01-01

We have obtained the 1.7 Å crystal structure of FIV protease (PR) in which 12 critical residues around the active site have been substituted with the structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV mutants [1-4]. Biochemical analyses have demonstrated that TL-3 inhibits these PRs in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and 41 nM, respectively [2-4]. Comparison of the crystal structures of the TL-3 complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV PR retained the hydrogen bonding interactions between residues in the flap regions and active site involving the enzyme and the TL-3 inhibitor in comparison to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more closely resemble those of HIV PR, having gained several stabilizing intra-flap interactions not present in wild type FIV PR. These findings offer a structural explanation for the observed inhibitor/substrate binding properties of the chimeric PR. PMID:17212810

Autonomous Underwater Vehicle Planning for Information Exploitation

DTIC Science & Technology

2012-03-01

probabilistic analysis process. 173 %********************************************************************** 174 175 global OG SnrImg PrOpoly PrEpoly 176...and Calculate Information Gain 193 194 [IGC1]=OGupdate(SnrImg, PrOpoly ,PrEpoly); % IGC1: IG Calculation 195 IG=IGC1; 196 197 %% Stern Points used for...PrOmdlfunc and 10 % PrEmdlfunc. 11 12 % The pdf’s may be plotted by uncommenting the plotting code in the last 13 % cell. 14 15 global PrOpoly PrEpoly 16 17

Prevalence of actual uptake and willingness to use pre-exposure prophylaxis to prevent HIV acquisition among men who have sex with men in Hong Kong, China

PubMed Central

Lau, Joseph T. F.; Fang, Yuan; Ip, Mary; Gross, Danielle L.

2018-01-01

Objectives This study was to investigate the prevalence of actual uptake of pre-exposure prophylaxis (PrEP), willingness to use daily oral PrEP under two cost scenarios, and potential issues related to PrEP use among men who have sex with men (MSM) with HIV negative/unknown sero-status in Hong Kong, China. Factors associated with the two measures of willingness were also investigated. Methods 403 eligible MSM completed the anonymous venue-based face-to-face interview/telephone interview. Results Only 1% had ever used PrEP. After being briefed about some facts of PrEP, the prevalence of willingness to use daily oral PrEP was 7.7% if they could purchase PrEP at private hospitals/clinics at HK$8,000 (US$1,032)/month (market rate) and 45.2% if free PrEP was provided by public hospitals/clinics in Hong Kong (free PrEP). After adjusted for significant background variables, significant factors of these two measures of willingness included: (1) number of correct responses to knowledge on PrEP, (2) perceived risk of HIV infection in the next six months, and (3) constructs of the Theory of Planned Behavior: positive and negative attitudes toward PrEP, perceived their significant others would support them take PrEP (perceived subjective norm), perceived number of local MSM who were willing to take PrEP (perceived descriptive norm), and confidence in using PrEP under the two scenarios (perceived behavioral control). Among all participants, 9.7% and 25.1% would start and discontinue using PrEP without consulting doctors; 26.0% would not take PrEP daily if it was provided for free, and 42.4% would not take up HIV testing every 3 months after using PrEP. Conclusion Different strategies should be considered for promoting PrEP at market rate and if free PrEP is made available. Future promotion should increase their knowledge about PrEP, modify their perceptions related to HIV and PrEP, and address some potential issues related to PrEP use. PMID:29432470

Manganite perovskite ceramics, their precursors and methods for forming

DOEpatents

Payne, David Alan; Clothier, Brent Allen

2015-03-10

Disclosed are a variety of ceramics having the formula Ln.sub.1-xM.sub.xMnO.sub.3, where 0.Itoreq.x.Itoreq.1 and where Ln is La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu or Y; M is Ca, Sr, Ba, Cd, or Pb; manganite precursors for preparing the ceramics; a method for preparing the precursors; and a method for transforming the precursors into uniform, defect-free ceramics having magnetoresistance properties. The manganite precursors contain a sol and are derived from the metal alkoxides: Ln(OR).sub.3, M(OR).sub.2 and Mn(OR).sub.2, where R is C.sub.2 to C.sub.6 alkyl or C.sub.3 to C.sub.9 alkoxyalkyl, or C.sub.6 to C.sub.9 aryl. The preferred ceramics are films prepared by a spin coating method and are particularly suited for incorporation into a device such as an integrated circuit device.

Characterization and long term operation of a novel superconducting undulator with 15 mm period length in a synchrotron light source

NASA Astrophysics Data System (ADS)

Casalbuoni, S.; Cecilia, A.; Gerstl, S.; Glamann, N.; Grau, A. W.; Holubek, T.; Meuter, C.; de Jauregui, D. Saez; Voutta, R.; Boffo, C.; Gerhard, Th.; Turenne, M.; Walter, W.

2016-11-01

A new cryogen-free full scale (1.5 m long) superconducting undulator with a period length of 15 mm (SCU15) has been successfully tested in the ANKA storage ring. This represents a very important milestone in the development of superconducting undulators for third and fourth generation light sources carried on by the collaboration between the Karlsruhe Institute of Technology and the industrial partner Babcock Noell GmbH. SCU15 is the first full length device worldwide that with beam reaches a higher peak field than what expected with the same geometry (vacuum gap and period length) with an ideal cryogenic permanent magnet undulator built with the best material available PrFeB. After a summary on the design and main parameters of the device, we present here the characterization in terms of spectral properties and the long term operation of the SCU15 in the ANKA storage ring.

Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.

PubMed

Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

2016-07-07

Prions are formed of misfolded assemblies (PrP(Sc)) of the variably N-glycosylated cellular prion protein (PrP(C)). In infected species, prions replicate by seeding the conversion and polymerization of host PrP(C). Distinct prion strains can be recognized, exhibiting defined PrP(Sc) biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrP(Sc) assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrP(C) glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrP(C) species of interest as substrate. Applying the technique to PrP(C) glycosylation mutants expressing cells revealed that neither PrP(C) nor PrP(Sc) glycoform stoichiometry was instrumental to PrP(Sc) formation and strainness perpetuation. Our study supports the view that strain properties, including PrP(Sc) glycotype are enciphered within PrP(Sc) structural backbone, not in the attached glycans.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seong, Yeon-Jae; Hafis Clinic, Seoul; Sung, Pil Soo

Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced themore » production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.« less

Recombinant PrPSc shares structural features with brain-derived PrPSc: Insights from limited proteolysis.

PubMed

Sevillano, Alejandro M; Fernández-Borges, Natalia; Younas, Neelam; Wang, Fei; R Elezgarai, Saioa; Bravo, Susana; Vázquez-Fernández, Ester; Rosa, Isaac; Eraña, Hasier; Gil, David; Veiga, Sonia; Vidal, Enric; Erickson-Beltran, Melissa L; Guitián, Esteban; Silva, Christopher J; Nonno, Romolo; Ma, Jiyan; Castilla, Joaquín; R Requena, Jesús

2018-01-01

Very solid evidence suggests that the core of full length PrPSc is a 4-rung β-solenoid, and that individual PrPSc subunits stack to form amyloid fibers. We recently used limited proteolysis to map the β-strands and connecting loops that make up the PrPSc solenoid. Using high resolution SDS-PAGE followed by epitope analysis, and mass spectrometry, we identified positions ~116/118, 133-134, 141, 152-153, 162, 169 and 179 (murine numbering) as Proteinase K (PK) cleavage sites in PrPSc. Such sites likely define loops and/or borders of β-strands, helping us to predict the threading of the β-solenoid. We have now extended this approach to recombinant PrPSc (recPrPSc). The term recPrPSc refers to bona fide recombinant prions prepared by PMCA, exhibiting infectivity with attack rates of ~100%. Limited proteolysis of mouse and bank vole recPrPSc species yielded N-terminally truncated PK-resistant fragments similar to those seen in brain-derived PrPSc, albeit with varying relative yields. Along with these fragments, doubly N- and C-terminally truncated fragments, in particular ~89/97-152, were detected in some recPrPSc preparations; similar fragments are characteristic of atypical strains of brain-derived PrPSc. Our results suggest a shared architecture of recPrPSc and brain PrPSc prions. The observed differences, in particular the distinct yields of specific PK-resistant fragments, are likely due to differences in threading which result in the specific biochemical characteristics of recPrPSc. Furthermore, recombinant PrPSc offers exciting opportunities for structural studies unachievable with brain-derived PrPSc.

Isolation of Novel Synthetic Prion Strains by Amplification in Transgenic Mice Coexpressing Wild-Type and Anchorless Prion Proteins

PubMed Central

Raymond, Gregory J.; Race, Brent; Hollister, Jason R.; Offerdahl, Danielle K.; Moore, Roger A.; Kodali, Ravindra; Raymond, Lynne D.; Hughson, Andrew G.; Rosenke, Rebecca; Long, Dan; Dorward, David W.

2012-01-01

Mammalian prions are thought to consist of misfolded aggregates (protease-resistant isoform of the prion protein [PrPres]) of the cellular prion protein (PrPC). Transmissible spongiform encephalopathy (TSE) can be induced in animals inoculated with recombinant PrP (rPrP) amyloid fibrils lacking mammalian posttranslational modifications, but this induction is inefficient in hamsters or transgenic mice overexpressing glycosylphosphatidylinositol (GPI)-anchored PrPC. Here we show that TSE can be initiated by inoculation of misfolded rPrP into mice that express wild-type (wt) levels of PrPC and that synthetic prion strain propagation and selection can be affected by GPI anchoring of the host's PrPC. To create prions de novo, we fibrillized mouse rPrP in the absence of molecular cofactors, generating fibrils with a PrPres-like protease-resistant banding profile. These fibrils induced the formation of PrPres deposits in transgenic mice coexpressing wt and GPI-anchorless PrPC (wt/GPI−) at a combined level comparable to that of PrPC expression in wt mice. Secondary passage into mice expressing wt, GPI−, or wt plus GPI− PrPC induced TSE disease with novel clinical, histopathological, and biochemical phenotypes. Contrary to laboratory-adapted mouse scrapie strains, the synthetic prion agents exhibited a preference for conversion of GPI− PrPC and, in one case, caused disease only in GPI− mice. Our data show that novel TSE agents can be generated de novo solely from purified mouse rPrP after amplification in mice coexpressing normal levels of wt and anchorless PrPC. These observations provide insight into the minimal elements required to create prions in vitro and suggest that the PrPC GPI anchor can modulate the propagation of synthetic TSE strains. PMID:22915801

The activities of progesterone receptor isoform A and B are differentially modulated by their ligands in a gene-selective manner.

PubMed

Leo, Joyce C L; Lin, Valerie C L

2008-01-01

It is known that progesterone receptor (PR) isoform A (PR-A) and isoform B (PR-B) may mediate different effects of progesterone. The objective of this study was to determine if the functions of PR isoforms also vary in response to different PR modulators (PRM). The effects of 7 synthetic PRM were tested in MDA-MB-231 cells engineered to express PR-A, PR-B, or both PR isoforms. The effects of progesterone were similar in cells expressing PR-A or PR-B in which it inhibited growth and induced focal adhesion. On the other hand, synthetic PRM modulated the activity of the PR isoforms differently. RU486, CDB4124, 17alpha-hydroxy CDB4124 and VA2914 exerted agonist activities on cell growth and adhesion via PR-B. Via PR-A, however, these compounds displayed agonist effect on cell growth but induced stellate morphology which was distinct from the agonist's effect. Their dual properties via PR-A were also displayed at the gene expression level: the compounds acted as agonists on cell cycle genes but exhibited antagonistic effect on cell adhesion genes. Introduction of ERalpha by adenoviral vector to these cells did not change PR-A or PR-B mediated effect of PRM radically, but it causes significant cell rounding and modified the magnitudes of the responses to PRM. The findings suggest that the activities of PR isoforms may be modulated by different PRM through gene-specific regulatory mechanisms. This raises an interesting possibility that PRM may be designed to be PR isoform and cellular pathway selective to achieve targeted therapy in breast cancer. Copyright 2007 Wiley-Liss, Inc.

"Since both of us are using antiretrovirals, we have been supportive to each other": facilitators and barriers of pre-exposure prophylaxis use in heterosexual HIV serodiscordant couples in Kisumu, Kenya.

PubMed

Patel, Rena C; Stanford-Moore, Gaelen; Odoyo, Josephine; Pyra, Maria; Wakhungu, Imeldah; Anand, Keerthana; Bukusi, Elizabeth A; Baeten, Jared M; Brown, Joelle M

2016-01-01

Since 2015, the World Health Organization recommends pre-exposure prophylaxis (PrEP) for all persons at substantial risk for HIV, including HIV-uninfected partners in serodiscordant relationships in resource-limited settings. As PrEP moves from clinical trials to real-world use, understanding facilitators of and barriers to PrEP initiation and adherence is critical to successful PrEP implementation and rollout. We conducted 44 in-depth individual or couple interviews with 63 participants (30 without HIV and 33 with HIV) enrolled in the Partners Demonstration Project in Kisumu, Kenya, between August and September 2014. The semi-structured interviews discussed the following: 1) perceived advantages and disadvantages of antiretroviral therapy (ART)/PrEP; 2) reasons for accepting or declining ART/PrEP and 3) influence of prevention of transmission to partner or infant on ART/PrEP use. Transcripts from the interviews were iteratively analyzed using inductive content analysis. Our study identified three key factors that may facilitate initiation of PrEP in this population. First, participants using PrEP felt reduced stress and increased trust in their HIV serodiscordant relationships. Second, greater community-wide knowledge of PrEP was thought to likely increase PrEP acceptance. Third, greater education and counselling by providers on PrEP use was also considered to likely increase the adoption of PrEP. We also identified three key barriers to initiation of and adherence to PrEP. First, most participants who declined PrEP expressed doubts about the relative additional effectiveness of PrEP in combination with other prevention tools. Second, perceived stigma related to PrEP use was an important barrier to PrEP initiation. Third, many struggled with overcoming perceived side effects or logistical challenges of taking daily PrEP, particularly when they themselves were not ill. Leveraging the facilitators and overcoming barriers to PrEP uptake may enhance the successful rollout of PrEP among HIV serodiscordant couples in Kenya and other areas in sub-Saharan Africa, thereby reducing sexual transmission of HIV. Further research focused on how best to provide counselling on combination HIV prevention tools in the context of PrEP use is a crucial next step to delivering PrEP.

PrPc Does Not Mediate Internalization of PrPSc but Is Required at an Early Stage for De Novo Prion Infection of Rov Cells▿

PubMed Central

Paquet, Sophie; Daude, Nathalie; Courageot, Marie-Pierre; Chapuis, Jérôme; Laude, Hubert; Vilette, Didier

2007-01-01

We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. We demonstrate that abnormal PrP (PrPSc) and prion infectivity are efficiently internalized in Rov cells, whether or not PrPc is expressed. At odds with earlier studies implicating cellular heparan sulfates in PrPSc internalization, we failed to find any involvement of such molecules in Rov cells, indicating that prions can enter target cells by several routes. We further show that PrPSc taken up in the absence of PrPc was unable to promote efficient prion multiplication once PrPc expression was restored in the cells. This observation argues that interaction of PrPSc with PrPc has to occur early, in a specific subcellular compartment(s), and is consistent with the view that the first prion multiplication events may occur at the cell surface. PMID:17626095

Divergent prion strain evolution driven by PrPC expression level in transgenic mice

PubMed Central

Le Dur, Annick; Laï, Thanh Lan; Stinnakre, Marie-George; Laisné, Aude; Chenais, Nathalie; Rakotobe, Sabine; Passet, Bruno; Reine, Fabienne; Soulier, Solange; Herzog, Laetitia; Tilly, Gaëlle; Rézaei, Human; Béringue, Vincent; Vilotte, Jean-Luc; Laude, Hubert

2017-01-01

Prions induce a fatal neurodegenerative disease in infected host brain based on the refolding and aggregation of the host-encoded prion protein PrPC into PrPSc. Structurally distinct PrPSc conformers can give rise to multiple prion strains. Constrained interactions between PrPC and different PrPSc strains can in turn lead to certain PrPSc (sub)populations being selected for cross-species transmission, or even produce mutation-like events. By contrast, prion strains are generally conserved when transmitted within the same species, or to transgenic mice expressing homologous PrPC. Here, we compare the strain properties of a representative sheep scrapie isolate transmitted to a panel of transgenic mouse lines expressing varying levels of homologous PrPC. While breeding true in mice expressing PrPC at near physiological levels, scrapie prions evolve consistently towards different strain components in mice beyond a certain threshold of PrPC overexpression. Our results support the view that PrPC gene dosage can influence prion evolution on homotypic transmission. PMID:28112164

Production of a soluble recombinant prion protein fused to blue fluorescent protein without refolding or detergents in Escherichia coli cells.

PubMed

Arii, Yasuhiro; Yamaguchi, Hidenori; Fukuoka, Shin-Ichi

2007-10-01

The physiological function of prion proteins (PrP) remains unclear. To investigate the physiological relevance of PrP, we constructed a fusion protein of PrP with enhanced blue fluorescent protein (PrP-EBFP) to quantify the interaction of PrP with other molecules. Production of soluble PrP-EBFP was achieved by lowering the expression temperature in Escherichia coli (E. coli) cells to 15 degrees C. Soluble PrP-EBFP was purified on cation exchange and heparin-affinity columns to yield high purity protein. This is the first report of the preparation of soluble recombinant PrP without refolding following solubilization using denaturants or disruption using detergents. To confirm the integrity of PrP-EBFP, anisotropy was estimated under physiological conditions in the presence of heparin, which interacts with PrP. The dissociation constant was determined to be 0.88+/-0.07 microM. PrP-EBFP should be useful in the quantification of PrP interactions with other molecules.

Control of interfacial properties of Pr-oxide/Ge gate stack structure by introduction of nitrogen

NASA Astrophysics Data System (ADS)

Kato, Kimihiko; Kondo, Hiroki; Sakashita, Mitsuo; Nakatsuka, Osamu; Zaima, Shigeaki

2011-06-01

We have demonstrated the control of interfacial properties of Pr-oxide/Ge gate stack structure by the introduction of nitrogen. From C- V characteristics of Al/Pr-oxide/Ge 3N 4/Ge MOS capacitors, the interface state density decreases without the change of the accumulation capacitance after annealing. The TEM and TED measurements reveal that the crystallization of Pr-oxide is enhanced with annealing and the columnar structure of cubic-Pr 2O 3 is formed after annealing. From the depth profiles measured using XPS with Ar sputtering for the Pr-oxide/Ge 3N 4/Ge stack structure, the increase in the Ge component is not observed in a Pr-oxide film and near the interface between a Pr-oxide film and a Ge substrate. In addition, the N component segregates near the interface region, amorphous Pr-oxynitride (PrON) is formed at the interface. As a result, Pr-oxide/PrON/Ge stacked structure without the Ge-oxynitride interlayer is formed.

Using mass spectrometry and small molecule reagents to detect distinctive structural features of different prion conformations (strains)

USDA-ARS?s Scientific Manuscript database

A prion (PrPSc) is a conformer of a normal cellular prion protein (PrPC). Although they are isosequential, PrPSc is an infectious protein able to convert PrPC into the prion conformation and thereby propagate an infection. PrPC is monomeric while PrPSc is a multimer. PrPSc can adopt more than one co...

75 FR 62519 - Northern Illinois Gas Company; Lee 8 Storage Partnership; NorthWestern Corporation; The East Ohio...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-123-000; PR10-124-000; PR10-125-000; PR10-126-000;. PR10-127-000; PR10-128-000; PR10-129-000 (Not Consolidated)] Northern Illinois Gas Company; Lee 8 Storage Partnership; NorthWestern Corporation; The East Ohio Gas Company; UGI...

Pseudotetrahedral manganese complexes supported by the anionic tris(phosphino)borate ligand [PhBPiPr3

PubMed Central

Lu, Connie C.; Peters, Jonas C.

2008-01-01

This paper presents aspects of the coordination chemistry of mono- and divalent manganese complexes supported by the anionic tris(phosphino)borate ligand, [PhBPiPr3] (where [PhBPiPr3] = [PhB(CH2PiPr2)3]−). The Mn(II) halide complexes, [PhBPiPr3]MnCl (1 and [PhBPiPr3]MnI (2), have been characterized by X-ray diffraction, SQUID magnetometry, and EPR spectroscopy. Compound 2 serves as a precursor to a series of Mn azide, alkyl, and amide species: [PhBPiPr3]Mn(N3) (3), [PhBPiPr3]Mn(CH2Ph) (4), [PhBPiPr3]Mn(Me) (5), [PhBPiPr3]Mn(NH(2,6-iPr2-C6H3)) (6), [PhBPiPr3]Mn(dbabh) (7), and [PhBPiPr3]Mn(1-Ph(isoindolate)) (8). The complexes 2 – 8 feature a divalent-metal center and are pseudotetrahedral. They collectively represent an uncommon structural motif for low-coordinate, polyphosphine-supported Mn complexes. Two Mn(I) species have also been prepared. These include the Tl-Mn adduct, [PhBPiPr3]Tl-MnBr(CO)4 (9), and the octahedral complex [PhBPiPr3]Mn(CNtBu)3 (10). Some of our initial synthetic efforts to generate [PhBPiPr3]Mn≡Nx species are briefly described, as are DFT studies that probe the electronic viability of these types of multiply bonded target structures. PMID:17029370

Optimizing content for pre-exposure prophylaxis (PrEP) counseling for men who have sex with men: Perspectives of PrEP users and high-risk PrEP naïve men.

PubMed

Wade Taylor, S; Mayer, Kenneth H; Elsesser, Steven M; Mimiaga, Matthew J; O'Cleirigh, Conall; Safren, Steven A

2014-05-01

Existing trials of antiretroviral (ARV) medication as chemoprophylaxis against HIV reveal that the degree of protection is primarily dependent on product adherence. However, there is a lack of data on targets for behavioral interventions to improve adherence to ARV as prevention. Information from individuals who have used ARV as pre-exposure prophylaxis (PrEP) can inform behavioral intervention development. Thirty-nine HIV-uninfected MSM at high risk for HIV acquisition participated in one of four semi-structured focus groups. Two of the focus groups consisted of MSM who had been prescribed and used PrEP in the context of a clinical trial; the other two consisted of high-risk MSM who had not previously used PrEP. An in-depth, within-case/across-case content analysis resulted in six descriptive themes potentially salient for a PrEP adherence behavioral intervention: (1) motivations to use PrEP, (2) barriers to PrEP use, (3) facilitators to PrEP use, (4) sexual decision-making in the context of PrEP, (5) prospective PrEP education content, and, (6) perceived effective characteristics of PrEP delivery personnel. Addressing these themes in behavioral interventions in the context of prescribing PrEP may result in the optimal "packaging" public health programs that implement PrEP for high-risk MSM.

Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants

PubMed Central

Bedaiwy, Mohamed A.; Dahoud, Wissam; Skomorovska-Prokvolit, Yelena; Yi, Lijuan; Liu, James H.; Falcone, Tommaso; Hurd, William W.; Mesiano, Sam

2015-01-01

Background: Several studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis. Methods: This in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively. Results: The PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis. Conclusions: Endometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis. PMID:26037298

A novel copper(II) coordination at His186 in full-length murine prion protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Yasuko; Hiraoka, Wakako; Igarashi, Manabu

2010-04-09

To explore Cu(II) ion coordination by His{sup 186} in the C-terminal domain of full-length prion protein (moPrP), we utilized the magnetic dipolar interaction between a paramagnetic metal, Cu(II) ion, and a spin probe introduced in the neighborhood of the postulated binding site by the spin labeling technique (SDSL technique). Six moPrP mutants, moPrP(D143C), moPrP(Y148C), moPrP(E151C), moPrP(Y156C), moPrP(T189C), and moPrP(Y156C,H186A), were reacted with a methane thiosulfonate spin probe and a nitroxide residue (R1) was created in the binding site of each one. Line broadening of the ESR spectra was induced in the presence of Cu(II) ions in moPrP(Y148R1), moPrP(Y151R1), moPrP(Y156R1), andmore » moPrP(T189R1) but not moPrP(D143R1). This line broadening indicated the presence of electron-electron dipolar interaction between Cu(II) and the nitroxide spin probe, suggesting that each interspin distance was within 20 A. The interspin distance ranges between Cu(II) and the spin probes of moPrP(Y148R1), moPrP(Y151R1), moPrP(Y156R1), and moPrP(T189R1) were estimated to be 12.1 A, 18.1 A, 10.7 A, and 8.4 A, respectively. In moPrP(Y156R1,H186A), line broadening between Cu(II) and the spin probe was not observed. These results suggest that a novel Cu(II) binding site is involved in His186 in the Helix2 region of the C-terminal domain of moPrP{sup C}.« less

75 FR 61463 - The Narragansett Electric Company; Arcadia Gas Storage, LLC; Salt Plains Storage, LLC; Jefferson...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-05

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-114-000; Docket No. PR10-117-000; Docket No. PR10-118- 000; Docket No. PR10-119-000; Docket No. PR10-120-000; Docket No. PR10- 121-000; Docket No. PR10-122-000 (Not Consolidated)] The Narragansett Electric Company; Arcadia Gas Storage, LLC; Salt Plains Storage, LLC;...

75 FR 62519 - Rocky Mountain Natural Gas LLC; KeySpan Gas East Corporation; ECOP Gas Company, LLC; MGTC, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-130-000; PR10-131-000; PR10-132-000; PR10-133-000; PR10-134-000; PR10-135-000; PR10-136-000 (Not Consolidated)] Rocky Mountain.... Bose, Secretary. [FR Doc. 2010-25519 Filed 10-8-10; 8:45 am] BILLING CODE 6717-01-P ...

Prion disease tempo determined by host-dependent substrate reduction

PubMed Central

Mays, Charles E.; Kim, Chae; Haldiman, Tracy; van der Merwe, Jacques; Lau, Agnes; Yang, Jing; Grams, Jennifer; Di Bari, Michele A.; Nonno, Romolo; Telling, Glenn C.; Kong, Qingzhong; Langeveld, Jan; McKenzie, Debbie; Westaway, David; Safar, Jiri G.

2014-01-01

The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers of prion disease include accumulation of the misfolded prion protein (PrPSc), which is derived from its cellular precursor (PrPC), as well as downregulation of the PrP-like Shadoo (Sho) glycoprotein. Given the overlapping cellular environments for PrPC and Sho, we inferred that PrPC levels might also be altered as part of a host response during prion infection. Using rodent models, we found that, in addition to changes in PrPC glycosylation and proteolytic processing, net reductions in PrPC occur in a wide range of prion diseases, including sheep scrapie, human Creutzfeldt-Jakob disease, and cervid chronic wasting disease. The reduction in PrPC results in decreased prion replication, as measured by the protein misfolding cyclic amplification technique for generating PrPSc in vitro. While PrPC downregulation is not discernible in animals with unusually short incubation periods and high PrPC expression, slowly evolving prion infections exhibit downregulation of the PrPC substrate required for new PrPSc synthesis and as a receptor for pathogenic signaling. Our data reveal PrPC downregulation as a previously unappreciated element of disease pathogenesis that defines the extensive, presymptomatic period for many prion strains. PMID:24430187

Functional Knowledge of Pre-Exposure Prophylaxis for HIV Prevention Among Participants in a Web-Based Survey of Sexually Active Gay, Bisexual, and Other Men Who Have Sex With Men: Cross-Sectional Study

PubMed Central

2018-01-01

Background Awareness of pre-exposure prophylaxis (PrEP) for HIV prevention is increasing, but little is known about the functional knowledge of PrEP and its impact on willingness to use PrEP. Objective The objective of this study was to assess the functional knowledge of PrEP among a sample of gay, bisexual, and other men who have sex with men (MSM) participating in a Web-based survey of sexually active MSM. Methods Men at least 18 years old, residing in the United States, and reporting sex with a man in the previous 6 months were recruited through social networking websites. PrEP functional knowledge included the following 4 questions (1) efficacy of consistent PrEP use, (2) inconsistent PrEP use and effectiveness, (3) PrEP and condom use, and (4) effectiveness at reducing sexually transmitted infections (STIs). Ordinal logistic regression was used to identify respondent characteristics associated with PrEP functional knowledge. In a subsample of participants responding to HIV prevention questions, we compared willingness to use PrEP by response to PrEP functional knowledge using logistic regression analysis adjusted for age, race and ethnicity, and education level. Results Among 573 respondents, PrEP knowledge was high regarding adherence (488/573, 85.2%), condom use (532/573, 92.8%), and STIs (480/573, 83.8%), but only 252/573 (44.0%) identified the correct efficacy. Lower functional PrEP knowledge was associated with minority race/ethnicity (P=.005), lower education (P=.01), and not having an HIV test in the past year (P=.02). Higher PrEP knowledge was associated with willingness to use PrEP (P=.009). Younger age was not associated with higher PrEP functional knowledge or willingness to use PrEP. Conclusions PrEP knowledge was generally high in our study, including condom use and consistent use but may be lacking in higher risk MSM. The majority of respondents did not correctly identify PrEP efficacy with consistent use, which could impact motivation to seek out PrEP for HIV prevention. Targeted messaging to increase PrEP knowledge may increase PrEP use. PMID:29362213

Flow Cytometric Detection of PrPSc in Neurons and Glial Cells from Prion-Infected Mouse Brains.

PubMed

Yamasaki, Takeshi; Suzuki, Akio; Hasebe, Rie; Horiuchi, Motohiro

2018-01-01

In prion diseases, an abnormal isoform of prion protein (PrP Sc ) accumulates in neurons, astrocytes, and microglia in the brains of animals affected by prions. Detailed analyses of PrP Sc -positive neurons and glial cells are required to clarify their pathophysiological roles in the disease. Here, we report a novel method for the detection of PrP Sc in neurons and glial cells from the brains of prion-infected mice by flow cytometry using PrP Sc -specific staining with monoclonal antibody (MAb) 132. The combination of PrP Sc staining and immunolabeling of neural cell markers clearly distinguished neurons, astrocytes, and microglia that were positive for PrP Sc from those that were PrP Sc negative. The flow cytometric analysis of PrP Sc revealed the appearance of PrP Sc -positive neurons, astrocytes, and microglia at 60 days after intracerebral prion inoculation, suggesting the presence of PrP Sc in the glial cells, as well as in neurons, from an early stage of infection. Moreover, the kinetic analysis of PrP Sc revealed a continuous increase in the proportion of PrP Sc -positive cells for all cell types with disease progression. Finally, we applied this method to isolate neurons, astrocytes, and microglia positive for PrP Sc from a prion-infected mouse brain by florescence-activated cell sorting. The method described here enables comprehensive analyses specific to PrP Sc -positive neurons, astrocytes, and microglia that will contribute to the understanding of the pathophysiological roles of neurons and glial cells in PrP Sc -associated pathogenesis. IMPORTANCE Although formation of PrP Sc in neurons is associated closely with neurodegeneration in prion diseases, the mechanism of neurodegeneration is not understood completely. On the other hand, recent studies proposed the important roles of glial cells in PrP Sc -associated pathogenesis, such as the intracerebral spread of PrP Sc and clearance of PrP Sc from the brain. Despite the great need for detailed analyses of PrP Sc -positive neurons and glial cells, methods available for cell type-specific analysis of PrP Sc have been limited thus far to microscopic observations. Here, we have established a novel high-throughput method for flow cytometric detection of PrP Sc in cells with more accurate quantitative performance. By applying this method, we succeeded in isolating PrP Sc -positive cells from the prion-infected mouse brains via fluorescence-activated cell sorting. This allows us to perform further detailed analysis specific to PrP Sc -positive neurons and glial cells for the clarification of pathological changes in neurons and pathophysiological roles of glial cells. Copyright © 2017 American Society for Microbiology.

Young Transgender Women's Attitudes Toward HIV Pre-exposure Prophylaxis.

PubMed

Wood, Sarah M; Lee, Susan; Barg, Frances K; Castillo, Marne; Dowshen, Nadia

2017-05-01

Our primary aim was to explore themes regarding attitudes toward HIV pre-exposure prophylaxis (PrEP) among young transgender women (YTW), in order to develop a theoretical model of PrEP uptake in this population disproportionally affected by HIV. Qualitative study nested within a mixed-method study characterizing barriers and facilitators to health services for YTW. Participants completed an in-depth interview exploring awareness of and attitudes toward PrEP. Key themes were identified using a grounded theory approach. Participants (n = 25) had a mean age of 21.2 years (standard deviation 2.2, range 17-24) and were predominately multiracial (36%) and of HIV-negative or unknown status (68%). Most participants (64%) reported prior knowledge of PrEP, and 28% reported current use or intent to use PrEP. Three major content themes that emerged were variability of PrEP awareness, barriers and facilitators to PrEP uptake, and emotional benefits of PrEP. Among participants without prior PrEP knowledge, participants reported frustration that PrEP information has not been widely disseminated to YTW, particularly by health care providers. Attitudes toward PrEP were overwhelmingly positive; however, concerns were raised regarding barriers including cost, stigma, and adherence challenges. Both HIV-positive and negative participants discussed emotional and relationship benefits of PrEP, which were felt to extend beyond HIV prevention alone. A high proportion of YTW in this study had prior knowledge of PrEP, and attitudes toward PrEP were positive among participants. Our findings suggest several domains to be further explored in PrEP implementation research, including methods of facilitating PrEP dissemination and emotional motivation for PrEP uptake. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

PrEP awareness and decision-making for Latino MSM in San Antonio, Texas

PubMed Central

García, Moctezuma; Harris, Allyssa L.

2017-01-01

Pre-Exposure Prophylaxis (PrEP) has been promoted among high-risk populations as an effective HIV biomedical intervention. However, limited research is available on the significance of culturally informed biomedical interventions for Latino MSM. A total of 159 self-administered Internet surveys were completed by Latino MSM ages 21–30 in San Antonio, Texas. The purpose of this research was to develop an instrument that measured Latino MSM attitudes and beliefs towards PrEP, identify associations between demographic factors and PrEP related factors and to suggest culturally appropriate strategies for the promotion of PrEP among the Latino MSM population. Research findings revealed implications for PrEP at the structural and individual level for Latino MSM. Structural level indicators emphasized the importance for raising PrEP awareness among Latino MSM in regards to PrEP related expenses, ameliorating stigmatization of high-risk populations, enhancing access to PrEP informed medical providers, and address mistrust of the government and medical providers role on addressing health disparities among Latino MSM. Overall, the findings for individual factors emphasize the need for patient-centered interventions for Latino MSM. Latino MSM currently on PrEP require supplemental resources to enhance PrEP adherence. Latino MSM not on PrEP require alternate options for PrEP delivery and/or cognitive behavioral approaches minimizing HIV risk behavior for Latino MSM concerned with PrEP toxicity, which may require non-biomedical interventions. Integration of Latino MSM currently on PrEP as peer educators provides a valuable resource for developing culturally informed PrEP interventions for Latino MSM. Peer educators are able to share their experiential knowledge of PrEP contextualized through cultural norms, beliefs, and values. PMID:28953905

The CNS glycoprotein Shadoo has PrPC-like protective properties and displays reduced levels in prion infections

PubMed Central

Watts, Joel C; Drisaldi, Bettina; Ng, Vivian; Yang, Jing; Strome, Bob; Horne, Patrick; Sy, Man-Sun; Yoong, Larry; Young, Rebecca; Mastrangelo, Peter; Bergeron, Catherine; Fraser, Paul E; Carlson, George A; Mount, Howard T J; Schmitt-Ulms, Gerold; Westaway, David

2007-01-01

The cellular prion protein, PrPC, is neuroprotective in a number of settings and in particular prevents cerebellar degeneration mediated by CNS-expressed Doppel or internally deleted PrP (‘ΔPrP'). This paradigm has facilitated mapping of activity determinants in PrPC and implicated a cryptic PrPC-like protein, ‘π'. Shadoo (Sho) is a hypothetical GPI-anchored protein encoded by the Sprn gene, exhibiting homology and domain organization similar to the N-terminus of PrP. Here we demonstrate Sprn expression and Sho protein in the adult CNS. Sho expression overlaps PrPC, but is low in cerebellar granular neurons (CGNs) containing PrPC and high in PrPC-deficient dendritic processes. In Prnp0/0 CGNs, Sho transgenes were PrPC-like in their ability to counteract neurotoxic effects of either Doppel or ΔPrP. Additionally, prion-infected mice exhibit a dramatic reduction in endogenous Sho protein. Sho is a candidate for π, and since it engenders a PrPC-like neuroprotective activity, compromised neuroprotective activity resulting from reduced levels may exacerbate damage in prion infections. Sho may prove useful in deciphering several unresolved facets of prion biology. PMID:17703189

In situ reaction mechanism studies on the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2}-D{sub 2}O and Ti(O{sup i}Pr){sub 3}[MeC(N{sup i}Pr){sub 2}]-D{sub 2}O atomic layer deposition processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomczak, Yoann, E-mail: yoann.tomczak@helsinki.fi; Knapas, Kjell; Leskelä, Markku

2014-01-15

Reaction mechanisms in the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2}-D{sub 2}O and Ti(O{sup i}Pr){sub 3}[MeC(N{sup i}Pr){sub 2}] [also written Ti(O{sup i}Pr){sub 3}(N{sup i}Pr-Me-amd)]-D{sub 2}O atomic layer deposition processes were studied in situ with quartz crystal microbalance (QCM) and quadrupole mass spectrometry (QMS) at 275 °C. For the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2}-D{sub 2}O process, both QCM and QMS results indicated adsorption of the Ti(NMe{sub 2}){sub 2}(O{sup i}Pr){sub 2} molecule through an exchange of at least one of its –NMe{sub 2} ligands with surface hydroxyl groups. Regarding the Ti(O{sup i}Pr){sub 3}(N{sup i}Pr-Me-amd)-D{sub 2}O process, a mismatch between the QCM and QMS results revealedmore » more complex reactions: the decomposition of the [MeC(N{sup i}Pr){sub 2}] [also written (N{sup i}Pr-Me-amd)] ligand is suggested by the shape of the QCM data and the intensity of the QMS signals belonging to fragments of the [MeC(N{sup i}Pr){sub 2}] [also written (N{sup i}Pr-Me-amd)] ligand. A simple calculation model associating the growth rate per cycle of a crystalline film and the surface area taken by the ligands remaining after saturation was also used to support the decomposition of the [MeC(N{sup i}Pr){sub 2}] [also written (N{sup i}Pr-Me-amd)] ligand. The observed high growth rate is incompatible with the whole [MeC(N{sup i}Pr){sub 2}] (also written [N{sup i}Pr-Me-amd)] ligand remaining on the surface.« less

Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation: A qualitative study.

PubMed

Bil, Janneke P; van der Veldt, Wendy M; Prins, Maria; Stolte, Ineke G; Davidovich, Udi

2016-09-01

Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM).Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach.Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients' medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support.To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling.

Motives of Dutch men who have sex with men for daily and intermittent HIV pre-exposure prophylaxis usage and preferences for implementation

PubMed Central

Bil, Janneke P.; van der Veldt, Wendy M.; Prins, Maria; Stolte, Ineke G.; Davidovich, Udi

2016-01-01

Abstract Although PrEP is not yet registered in Europe, including the Netherlands, its approval and implementation are expected in the near future. To inform future pre-exposure prophylaxis (PrEP) implementation, this study aimed to gain insight into motives and preferences for daily or intermittent PrEP use among Dutch HIV-negative men having sex with men (MSM). Between February and December 2013, semistructured interviews were conducted until data saturation was reached (N = 20). Interviews were analyzed using the Grounded Theory approach. Motives for (not) using daily PrEP were based on beliefs about PrEP efficacy and side effects, preferences for other prevention strategies, self-perceived HIV risk, self-perceived efficacy of PrEP adherence, beliefs about possible benefits (e.g., anxiety reduction, sex life improvement), and barriers of PrEP use (e.g., costs, monitoring procedures). The perceived benefits of intermittent versus daily PrEP use were the lower costs and side effects and the lower threshold to decision to start using intermittent PrEP. Barriers of intermittent PrEP versus daily PrEP use were the perceived need to plan their sex life and adhere to multiple prevention strategies. Although some perceived PrEP as a condom substitute, others were likely to combine PrEP and condoms for sexually transmitted infections (STI) prevention and increased HIV protection. Participants preferred PrEP service locations to have specialized knowledge of HIV, antiretroviral therapy, sexual behavior, STIs, patients’ medical background, be easily approachable, be able to perform PrEP follow-up monitoring, and provide support. To maximize the public health impact of PrEP, ensuring high uptake among MSM at highest risk is important. Therefore, targeted information about PrEP efficacy and side effects need to be developed, barriers for accessing PrEP services should be minimized, and perceived self-efficacy to use PrEP should be addressed and improved. To prevent increases in STIs, condom use should be monitored and PrEP should be integrated into routine STI screening and counseling. PMID:27684827

Demographic Differences in PrEP-Related Stereotypes: Implications for Implementation.

PubMed

Golub, Sarit A; Gamarel, Kristi E; Surace, Anthony

2017-05-01

Qualitative interviews about pre-exposure prophylaxis (PrEP) stereotypes were conducted with a subsample of 160 MSM who participated in a PrEP messaging study. Negative stereotypes about PrEP users were identified by 80 % of participants. Two types of stereotypes were most common: PrEP users are HIV-infected (and lying about it), and PrEP users are promiscuous and resistant to condom use. Participants' identification of these stereotype categories differed significantly by demographic factors (i.e., race/ethnicity, education). Expanding access to PrEP requires recognizing potential differences in the experience or anticipation of PrEP-related stereotypes that might impact willingness to discuss PrEP with providers, friends, or partners.

Demographic differences in PrEP–related stereotypes: Implications for implementation

PubMed Central

Golub, Sarit. A.; Gamarel, Kristi E.; Surace, Anthony

2015-01-01

Qualitative interviews about pre-exposure prophylaxis (PrEP) stereotypes were conducted with a subsample of 160 MSM who participated in a PrEP messaging study. Negative stereotypes about PrEP users were identified by 80% of participants. Two types of stereotypes were most common: PrEP users are HIV-infected (and lying about it), and PrEP users are promiscuous and resistant to condom use. Participants’ identification of these stereotype categories differed significantly by demographic factors (i.e. race/ethnicity, education). Expanding access to PrEP requires recognizing potential differences in the experience or anticipation of PrEP-related stereotypes that might impact willingness to discuss PrEP with providers, friends, or partners. PMID:26143247

Inflammatory Stimuli Increase Progesterone Receptor-A Stability and Transrepressive Activity in Myometrial Cells

PubMed Central

Peters, Gregory A.; Yi, Lijuan; Skomorovska-Prokvolit, Yelenna; Patel, Bansari; Amini, Peyvand; Tan, Huiqing

2017-01-01

The steroid hormone progesterone acting via the nuclear progesterone receptor (PR) isoforms, progesterone receptor A (PR-A) and progesterone receptor B (PR-B), is essential for the maintenance of uterine quiescence during pregnancy. Inhibition of PR signaling augments uterine contractility and induces labor. Human parturition is thought to be triggered by modulation of PR signaling in myometrial cells to induce a functional progesterone withdrawal. One mechanism for functional progesterone withdrawal is increased abundance of PR-A, which decreases progesterone responsiveness by inhibiting the transcriptional activity of PR-B. Human parturition also involves tissue-level inflammation within the myometrium. This study examined the control of PR-A abundance and transrepressive activity in myometrial cells and the role of the inflammatory stimuli in the form of interleukin-1β (IL-1β) and lipopolysaccharide (LPS) in these processes. We found that abundance of PR-A was markedly increased by progesterone and by exposure to IL-1β and LPS via posttranslational mechanisms involving increased PR-A protein stability. In contrast, progesterone decreased abundance of PR-B by increasing its rate of degradation. Together, progesterone and proinflammatory stimuli induced a PR-A–dominant state in myometrial cells similar to that observed in term laboring myometrium. IL-1β and LPS also increased the capacity for PR-A to inhibit the transcriptional activity of PR-B. Taken together, our data suggest that proinflammatory stimuli increase the steady-state levels of PR-A and its transrepressive activity in myometrial cells and support the hypothesis that tissue-level inflammation triggers parturition by inducing PR-A–mediated functional progesterone withdrawal. PMID:27886516

C-Terminal HIV-1 Transframe p6* Tetrapeptide Blocks Enhanced Gag Cleavage Incurred by Leucine Zipper Replacement of a Deleted p6* Domain.

PubMed

Yu, Fu-Hsien; Huang, Kuo-Jung; Wang, Chin-Tien

2017-05-15

HIV-1 protease (PR) functions as a homodimer mediating virus maturation following virus budding. Gag-Pol dimerization is believed to trigger embedded PR activation by promoting PR dimer formation. Early PR activation can lead to markedly reduced virus yields due to premature Gag cleavage. The p6* peptide, located between Gag and PR, is believed to ensure virus production by preventing early PR maturation. Studies aimed at finding supporting evidence for this proposal are limited due to a reading frame overlap between p6* and the p6gag budding domain. To determine if p6* affects virus production via the modulation of PR activation, we engineered multiple constructs derived from Dp6*PR (an assembly- and processing-competent construct with Pol fused at the inactivated PR C terminus). The data indicated that a p6* deletion adjacent to active PR significantly impaired virus processing. We also observed that the insertion of a leucine zipper (LZ) dimerization motif in the deleted region eliminated virus production in a PR activity-dependent manner, suggesting that the LZ insertion triggered premature PR activation by facilitating PR dimer formation. As few as four C-terminal p6* residues remaining at the p6*/PR junction were sufficient to restore virus yields, with a Gag processing profile similar to that of the wild type. Our study provides supporting evidence in a virus assembly context that the C-terminal p6* tetrapeptide plays a role in preventing premature PR maturation. IMPORTANCE Supporting evidence for the assumption that p6* retards PR maturation in the context of virus assembly is lacking. We found that replacing p6* with a leucine zipper peptide abolished virus assembly due to the significant enhancement of Gag cleavage. However, as few as four C-terminal p6* residues remaining in the deleted region were sufficient for significant PR release, as well as for counteracting leucine zipper-incurred premature Gag cleavage. Our data provide evidence that (i) p6* ensures virus assembly by preventing early PR activation and (ii) four C-terminal p6* residues are critical for modulating PR activation. Current PR inhibitor development efforts are aimed largely at mature PR, but there is a tendency for HIV-1 variants that are resistant to multiple protease inhibitors to emerge. Our data support the idea of modulating PR activation by targeting PR precursors as an alternative approach to controlling HIV-1/AIDS. Copyright © 2017 American Society for Microbiology.

78 FR 47056 - Proposed Collection; Comment Request for Forms 941, 941-PR, 941-SS, 941-X, 941-X(PR), Schedule B...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-02

... 941, 941-PR, 941- SS, 941-X, 941-X(PR), Schedule B (Form 941), Schedule R (Form 941)and Schedule B... Islands), 941-X, Adjusted Employer's Quarterly Federal Tax Return or Claim for Refund, 941-X(PR), Schedule...: 941, 941-PR, 941-SS, 941-X, 941-X(PR), Schedule R (Form 941), Schedule B (Form 941), and Schedule B...

Does methionine oxidation influence the progression of classical or atypical scrapie

USDA-ARS?s Scientific Manuscript database

Introduction Prions are pathological proteins that propagate by converting a normal cellular prion protein (PrPC) into a prion (PrPSc). PrPC and PrPSc possess identical covalent structures and only differ in their conformations. The conversion of the PrPC conformation to the PrPSc one is template ...

Cell-surface prion protein interacts with glycosaminoglycans.

PubMed Central

Pan, Tao; Wong, Boon-Seng; Liu, Tong; Li, Ruliang; Petersen, Robert B; Sy, Man-Sun

2002-01-01

We used ELISA and flow cytometry to study the binding of prion protein PrP to glycosaminoglycans (GAGs). We found that recombinant human PrP (rPrP) binds GAGs including chondroitin sulphate A, chondroitin sulphate B, hyaluronic acid, and heparin. rPrP binding to GAGs occurs via the N-terminus, a region known to bind divalent cations. Additionally, rPrP binding to GAGs is enhanced in the presence of Cu2+ and Zn2+, but not Ca2+ and Mn2+. rPrP binds heparin strongest, and the binding is inhibited by certain heparin analogues, including heparin disaccharide and sulphate-containing monosaccharides, but not by acetylated heparin. Full-length normal cellular prion protein (PrPC), but not N-terminally truncated PrPC species, from human brain bind GAGs in a similar Cu2+/Zn2+-enhanced fashion. We found that GAGs specifically bind to a synthetic peptide corresponding to amino acid residues 23-35 in the N-terminus of rPrP. We further demonstrated that while both wild-type PrPC and an octapeptide-repeat-deleted mutant PrP produced by transfected cells bound heparin at the cell surface, the PrP N-terminal deletion mutant and non-transfectant control failed to bind heparin. Binding of heparin to wild-type PrPC on the cell surface results in a reduction of the level of cell-surface PrPC. These results provide strong evidence that PrPC is a surface receptor for GAGs. PMID:12186633

Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells.

PubMed

Kawprasertsri, Sornsawan; Pietras, Richard J; Marquez-Garban, Diana C; Boonyaratanakornkit, Viroj

2016-05-01

Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BΔSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020-mediated inhibition of cell proliferation. Expression of PR-BΔSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BΔSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers

PubMed Central

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

Introduction HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Discussion Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Conclusions Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes. PMID:27760688

Enhancing HIV Pre-exposure, Prophylaxis Practices via an Educational Intervention.

PubMed

Newman, Rebecca; Katchi, Tasleem; Karass, Michael; Gennarelli, Melissa; Goutis, Jason; Kifayat, Alina; Solanki, Shantanu; Yandrapalli, Srikanth; Forman, Leanne; Nabors, Christopher

2018-04-20

Pre-exposure prophylaxis (PrEP) for HIV involves using antiretroviral drugs to prevent individuals at high risk from acquiring HIV infection. Most practicing primary care providers believe PrEP to be safe and effective, but less than half have prescribed or referred for PrEP. Attitudes and prescribing patterns among house officers have not been well described previously. Can an educational intervention enhance HIV PrEP practices among internal medicine house officers? This study relied on a pretest/posttest design. All categorical trainees at a medium-sized internal medicine program were offered a baseline survey to assess their knowledge on PrEP. This was followed by a PrEP-focused educational intervention and a postintervention survey. Likert scales captured perceptions regarding safety, effectiveness, barriers, factors that would promote PrEP use, potential side effects, impact on risk-taking behavior, and provider comfort level in assessing behavioral risks and in PrEP prescribing. Data were analyzed using descriptive statistics, Wilcoxon signed rank test, and the Kruskal-Wallis test. Significance was accepted for P < 0.05. Forty-eight (100%) trainees participated in the educational session, 45 (94%) in a preintervention survey, and 36 (75%) in a postintervention survey. Before PrEP training, 22% of respondents were unaware of PrEP, 78% believed PrEP was effective, 66% believed PrEP was safe, 62% had fair or poor awareness of side effects; 18% of residents had referred for or prescribed PrEP, and 31% believed they were likely to prescribe PrEP in the next 6 months. After the intervention, 94% of trainees believed PrEP was effective (P < 0.001), 92% believed PrEP was safe (P < 0.001), and two-thirds believed they were likely to prescribe PrEP in the next 6 months. Brief, focused training on HIV prevention promotes awareness, acceptance, and likelihood of prescribing PrEP by internal medicine trainees.

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers.

PubMed

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes.

Distinguishing hypothetical willingness from behavioral intentions to initiate HIV pre-exposure prophylaxis (PrEP): Findings from a large cohort of gay and bisexual men in the U.S.

PubMed

Rendina, H Jonathon; Whitfield, Thomas H F; Grov, Christian; Starks, Tyrel J; Parsons, Jeffrey T

2017-01-01

Much of the data on the acceptability of HIV Pre-Exposure Prophylaxis (PrEP) is based on willingness to take PrEP (i.e., hypothetical receptivity) rather than actual intentions (i.e., planned behavioral action) to do so. We sought to examine differences between hypothetical willingness and behavioral intentions to begin PrEP in a national sample of gay and bisexual men (GBM) across the U.S. We utilized data collected in 2015 to examine differences between those Unwilling (42.6% n = 375), Willing but not intending (41.4%, n = 365), and willing and Intending to take PrEP (15.9%, n = 140) in a multivariable, multinomial logistic regression. Men with less education had higher odds of Intending to take PrEP. Compared to men unsure about PrEP's efficacy, those who believed PrEP was at least 90% efficacious had higher odds of Intending to take PrEP. Those who saw themselves as appropriate candidates for PrEP had higher odds of Intending to take PrEP while those who saw themselves as inappropriate candidates for PrEP had lower odds of Intending to take PrEP in comparison to men unsure if they were appropriate candidates. Increased motivation for condom non-use because of perceived sexual pressure by partners was associated with higher odds of Intending to take PrEP. The groups did not differ by risk behavior nor recent STI diagnosis. Overall, the distinction between willingness and intentions to take PrEP was meaningful and may help explain disparities between PrEP acceptability and uptake. While much of the literature has focused on hypothetical willingness to take PrEP, these results highlight the importance of simultaneously assessing willingness and intentions when examining correspondence with uptake and developing interventions to increase PrEP uptake. Copyright © 2016 Elsevier Ltd. All rights reserved.

pH-Responsive Hydrogel With an Anti-Glycation Agent for Modulating Experimental Periodontitis.

PubMed

Yu, Min-Chen; Chang, Chih-Yeun; Chao, Yi-Chi; Jheng, Yi-Han; Yang, Connie; Lee, Ning; Yu, Shan-Huey; Yu, Xin-Hong; Liu, Dean-Mo; Chang, Po-Chun

2016-06-01

Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan-based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix. A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature-induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density. PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal. Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis.

Thermodynamics of reaction of praseodymium with gallium-indium eutectic alloy

NASA Astrophysics Data System (ADS)

Melchakov, S. Yu.; Ivanov, V. A.; Yamshchikov, L. F.; Volkovich, V. A.; Osipenko, A. G.; Kormilitsyn, M. V.

2013-06-01

Thermodynamic properties of Ga-In eutectic alloys saturated with praseodymium were determined for the first time employing the electromotive force method. The equilibrium potentials of the Pr-In alloys saturated with praseodymium (8.7-12.1 mol.% Pr) and Pr-Ga-In alloys (containing 0.0012-6.71 mol.% Pr) were measured between 573-1073 K. Pr-In alloy containing solid PrIn3 with known thermodynamic properties was used as the reference electrode when measuring the potentials of ternary Pr-In-Ga alloys. Activity, partial and excessive thermodynamic functions of praseodymium in alloys with indium and Ga-In eutectic were calculated. Activity (a), activity coefficients (γ) and solubility (X) of praseodymium in the studied temperature range can be expressed by the following equations: lgaα-Pr(In) = 4.425 - 11965/T ± 0.026. lgаα-Pr(Ga-In) = 5.866 - 14766/T ± 0.190. lgγα-Pr(Ga-In) = 2.351 - 9996/T ± 0.39. lgХPr(Ga-In) = 3.515 - 4770/T ± 0.20.

Preliminary investigation of foot pressure distribution variation in men and women adults while standing.

PubMed

Periyasamy, R; Mishra, A; Anand, Sneh; Ammini, A C

2011-09-01

Women and men are anatomically and physiologically different in a number of ways. They differ in both shape and size. These differences could potentially mean foot pressure distribution variation in men and women. The purpose of this study was to analyze standing foot pressure image to obtain the foot pressure distribution parameter - power ratio variation between men and women using image processing in frequency domain. We examined 28 healthy adult subjects (14 men and 14 women) aged between 20 and 45 years was recruited for our study. Foot pressure distribution patterns while standing are obtained by using a PedoPowerGraph plantar pressure measurement system for foot image formation, a digital camera for image capturing, a TV tuner PC-add on card, a WinDvr software for still capture and Matlab software with dedicated image processing algorithms have been developed. Various PedoPowerGraphic parameters such as percentage medial impulse (PMI), fore foot to hind foot pressure distribution ratio (F/H), big toe to fore foot pressure distribution ratio (B/F) and power ratio (PR) were evaluated. In men, contact area was significantly larger in all regions of the foot compared with women. There were significant differences in plantar pressure distribution but there was no significant difference in F/H and B/F ratio. Mean PR value was significantly greater in men than women under the hind foot and fore foot. PMI value was greater in women than men. As compared to men, women have maximum PR variations in the mid foot. Hence there is significant difference at level p<0.05 in medial mid foot and mid foot PR of women as compared to men. There was variation in plantar pressure distribution because the contact area of the men foot was larger than that of women foot. Hence knowledge of pressure distributions variation of both feet can provide suitable guidelines to biomedical engineers and doctor for designing orthotic devices for reliving the area of excessively high pressure. Copyright © 2011 Elsevier Ltd. All rights reserved.

Experimental Investigation of the Cd-Pr Phase Diagram

PubMed Central

Reichmann, Thomas L.; Effenberger, Herta S.; Ipser, Herbert

2014-01-01

The complete Cd-Pr equilibrium phase diagram was investigated with a combination of powder-XRD, SEM and DTA. All intermetallic compounds within this system, already reported in literature, could be confirmed: CdPr, Cd2Pr, Cd3Pr, Cd45Pr11, Cd58Pr13, Cd6Pr and Cd11Pr. The corresponding phase boundaries were determined at distinct temperatures. The homogeneity range of the high-temperature allotropic modification of Pr could be determined precisely and a limited solubility of 22.1 at.% Cd was derived. Additionally, single-crystal X-ray diffraction was employed to investigate structural details of Cd2Pr; it is isotypic to the AlB2-type structure with a z value of the Cd site of 0.5. DTA results of alloys located in the adjacent two-phase fields of Cd2Pr suggested a phase transformation between 893 and 930°C. For the phase Cd3Pr it was found that the lattice parameter a changes linearly with increasing Cd content, following Vegard’s rule. The corresponding defect mechanism could be evaluated from structural data collected with single-crystal XRD. Introduction of a significant amount of vacancies on the Pr site and the reduction in symmetry of one Cd position (8c to 32f) resulted in a noticeable decrease of all R-values. PMID:24718502

Generic amyloidogenicity of mammalian prion proteins from species susceptible and resistant to prions.

PubMed

Nyström, Sofie; Hammarström, Per

2015-05-11

Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Although PrP is highly conserved and ubiquitously expressed in all mammals, not all species exhibit prion disease. By employing full length recombinant PrP from five known prion susceptible species (human, cattle, cat, mouse and hamster) and two species considered to be prion resistant (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the mammalian PrPs, even from resistant species, were swiftly converted from the native state to amyloid-like structure when subjected to a native condition conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Fibrils from Aβ1-40, Aβ1-42, Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of all PrPs efficiently seeded conversion showing specificity of the assay requiring the C-terminal PrP sequence. Our findings have implications for PrP misfolding and could have ramifications in the context of prion resistant species and silent carriers.

Recombinant Prion Protein Refolded with Lipid and RNA Has the Biochemical Hallmarks of a Prion but Lacks In Vivo Infectivity

PubMed Central

Timmes, Andrew G.; Moore, Roger A.; Fischer, Elizabeth R.; Priola, Suzette A.

2013-01-01

During prion infection, the normal, protease-sensitive conformation of prion protein (PrPC) is converted via seeded polymerization to an abnormal, infectious conformation with greatly increased protease-resistance (PrPSc). In vitro, protein misfolding cyclic amplification (PMCA) uses PrPSc in prion-infected brain homogenates as an initiating seed to convert PrPC and trigger the self-propagation of PrPSc over many cycles of amplification. While PMCA reactions produce high levels of protease-resistant PrP, the infectious titer is often lower than that of brain-derived PrPSc. More recently, PMCA techniques using bacterially derived recombinant PrP (rPrP) in the presence of lipid and RNA but in the absence of any starting PrPSc seed have been used to generate infectious prions that cause disease in wild-type mice with relatively short incubation times. These data suggest that lipid and/or RNA act as cofactors to facilitate the de novo formation of high levels of prion infectivity. Using rPrP purified by two different techniques, we generated a self-propagating protease-resistant rPrP molecule that, regardless of the amount of RNA and lipid used, had a molecular mass, protease resistance and insolubility similar to that of PrPSc. However, we were unable to detect prion infectivity in any of our reactions using either cell-culture or animal bioassays. These results demonstrate that the ability to self-propagate into a protease-resistant insoluble conformer is not unique to infectious PrP molecules. They suggest that the presence of RNA and lipid cofactors may facilitate the spontaneous refolding of PrP into an infectious form while also allowing the de novo formation of self-propagating, but non-infectious, rPrP-res. PMID:23936256

Pre-Exposure Prophylaxis (PrEP) Use and Condomless Anal Sex: Evidence of Risk Compensation in a Cohort of Young Men Who Have Sex with Men.

PubMed

Newcomb, Michael E; Moran, Kevin; Feinstein, Brian A; Forscher, Emily; Mustanski, Brian

2018-04-01

Young men who have sex with men (YMSM) are disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV acquisition. It remains unclear if PrEP use increases rates of condomless sex (ie, risk compensation), which may increase risk of infection if PrEP adherence is not optimal. This study aimed to examine whether PrEP use and PrEP adherence were associated with change in sexual risk behaviors in a large longitudinal cohort of YMSM reporting on multiple sexual partnerships over time. Data were obtained from the first 3 visits of an ongoing cohort study of YMSM in Chicago (analytic N = 953; 14.1% HIV-positive at baseline). Participants reported up to 4 sexual partnerships at each visit, including sexual behavior, PrEP use, and PrEP adherence within partnerships. YMSM reported higher rates of receptive condomless anal sex (CAS) in partnerships during which they were on PrEP compared with those when they were not on PrEP. This association was consistent across both HIV-negative and HIV-positive participants reporting on partnerships with both perceived HIV-negative/unknown and HIV-positive partners. The rate of receptive CAS was higher in PrEP nonadherent partnerships compared with non-PrEP partnerships. The rate of receptive CAS was also higher in PrEP nonadherent than adherent partnerships, but this was not statistically significant. These analyses provide compelling data suggesting that YMSM are engaging in risk compensation when on PrEP. If rates of receptive CAS are highest among YMSM who are PrEP nonadherent, PrEP as a prevention strategy could fail to curb HIV incidence among YMSM.

Release of Full-Length PrPC from Cultured Neurons Following Neurotoxic Challenge

PubMed Central

Wang, Kevin K. W.; Zoltewicz, J. Susie; Chiu, Allen; Zhang, Zhiqun; Rubenstein, Richard

2012-01-01

The susceptibility of the normal cellular prion protein isoform, cellular prion protein (PrPC), to proteolytic digestion has been well documented. In addition, a link between PrPC and the cytosolic protease, calpain, has been reported although the specifics of the interaction remain unclear. We performed in vitro and in cell-based studies to examine this relationship. We observed that human recombinant PrP (HrPrP) was readily cleaved by calpain-1 and -2, and we have identified and defined the targeted cleavage sites. In contrast, HrPrP was resistant to caspase-3 digestion. Unexpectedly, when brain lysates from PrPC-expressing mice were treated with calpain, no appreciable loss of the intact PrPC, nor the appearance of PrPC breakdown products (BDPs) were observed, even though alpha II-spectrin was converted to its signature calpain-induced BDPs. In addition, when rat cerebrocortical neuronal cultures (RtCNC) were subjected to the two neurotoxins at subacute levels, maitotoxin (MTX) and N-methyl-d-aspartate (NMDA), PrPC-BDPs were also not detectable. However, a novel finding from these cell-based studies is that apparently full-length, mature PrPC is released into culture media from RtCNC challenged with subacute doses of MTX and NMDA. Calpain inhibitor SNJ-1945 and caspase inhibitor IDN-6556 did not attenuate the release of PrPC. Similarly, the lysosomal protease inhibitor, NH4Cl, and the proteasome inhibitor, lactacystin, did not significantly alter the integrity of PrPC or its release from the RtCNC. In conclusion, rat neuronal PrPC is not a significant target for proteolytic modifications during MTX and NMDA neurotoxic challenges. However, the robust neurotoxin-mediated release of full-length PrPC into the cell culture media suggests an unidentified neuroprotective mechanism for PrPC. PMID:23093947

Pre-Exposure Prophylaxis: A Narrative Review of Provider Behavior and Interventions to Increase PrEP Implementation in Primary Care.

PubMed

Silapaswan, Andrew; Krakower, Douglas; Mayer, Kenneth H

2017-02-01

Since FDA approval of HIV pre-exposure prophylaxis (PrEP) for HIV prevention, attention has been focused on PrEP implementation. The CDC estimates that 1.2 million U.S. adults might benefit from PrEP, but only a minority are using PrEP, so there is a significant unmet need to increase access for those at risk for HIV. Given the large numbers of individuals who have indications for PrEP, there are not enough practicing specialists to meet the growing need for providers trained in providing PrEP. Moreover, since PrEP is a preventive intervention for otherwise healthy individuals, primary care providers (PCPs) should be primary prescribers of PrEP. There are important clinical considerations that providers should take into account when planning to prescribe PrEP, which are highlighted in the clinical case discussed. A growing body of research also suggests that some providers may be cautious about prescribing PrEP because of concerns regarding its "real-world" effectiveness, anticipated unintended consequences associated with its use, and ambiguity as to who should prescribe it. This review summarizes findings from studies that have assessed prescriber behavior regarding provision of PrEP, and offers recommendations on how to optimize PrEP implementation in primary care settings. Development and dissemination of educational interventions for PCPs and potential PrEP users are needed, including improved methods to assist clinicians in identifying appropriate PrEP candidates, and programs to promote medication adherence and access to social and behavioral health services. PCPs are well-positioned to prescribe PrEP and coordinate health-related services to improve the sexual health of their patients, but tailored educational programs are needed.

Pressure-assisted dissociation and degradation of "proteinase K-resistant" fibrils prepared by seeding with scrapie-infected hamster prion protein.

PubMed

Akasaka, Kazuyuki; Maeno, Akihiro; Murayama, Taichi; Tachibana, Hideki; Fujita, Yuzo; Yamanaka, Hitoki; Nishida, Noriyuki; Atarashi, Ryuichiro

2014-01-01

The crucial step for the fatal neurodegenerative prion diseases involves the conversion of a normal cellular protein, PrP(C), into a fibrous pathogenic form, PrP(Sc), which has an unusual stability against heat and resistance against proteinase K digestion. A successful challenge to reverse the reaction from PrP(Sc) into PrP(C) is considered valuable, as it would give a key to dissolving the complex molecular events into thermodynamic and kinetic analyses and may also provide a means to prevent the formation of PrP(Sc) from PrP(C) eventually in vivo. Here we show that, by applying pressures at kbar range, the "proteinase K-resistant" fibrils (rHaPrP(res)) prepared from hamster prion protein (rHaPrP [23-231]) by seeding with brain homogenate of scrapie-infected hamster, becomes easily digestible. The result is consistent with the notion that rHaPrP(res) fibrils are dissociated into rHaPrP monomers under pressure and that the formation of PrP(Sc) from PrP(C) is thermodynamically controlled. Moreover, the efficient degradation of prion fibrils under pressure provides a novel means of eliminating infectious PrP(Sc) from various systems of pathogenic concern.

Engaging healthcare providers to implement HIV pre-exposure prophylaxis.

PubMed

Krakower, Douglas; Mayer, Kenneth H

2012-11-01

Recent randomized controlled trials have demonstrated that HIV pre-exposure prophylaxis (PrEP) can decrease HIV incidence among several at-risk populations, including men who have sex with men, serodiscordant couples, and heterosexual men and women. As PrEP is a biomedical intervention that requires clinical monitoring and a high level of medication adherence, maximizing the public health effectiveness of PrEP in real-world settings will require the training of a cadre of healthcare providers to prescribe PrEP. Therefore it is critical to understand provider knowledge, practices, and attitudes towards PrEP prescribing, and to develop strategies for engaging and training providers to provide PrEP. Limited numbers of studies have focused on PrEP implementation by healthcare providers. These studies suggest that some providers are knowledgeable about PrEP, but many are not, or express misgivings. Although many clinicians report willingness to provide PrEP, few have prescribed PrEP in clinical practice. Provider comfort and skills in HIV risk assessment are suboptimal, which could limit identification of individuals who are most likely to benefit from PrEP use. Further studies to understand facilitators and barriers to HIV-risk assessment and PrEP prescribing by practicing clinicians are needed. Innovative training strategies and decision-support interventions for providers could optimize PrEP implementation and therefore merit additional research.

Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.

PubMed

Zhang, Guoqi; Yang, Li; Kim, Gab Seok; Ryan, Kieran; Lu, Shulin; O'Donnell, Rebekah K; Spokes, Katherine; Shapiro, Nathan; Aird, William C; Kluk, Michael J; Yano, Kiichiro; Sanchez, Teresa

2013-07-18

The endothelium, as the interface between blood and all tissues, plays a critical role in inflammation. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid, highly abundant in plasma, that potently regulates endothelial responses through interaction with its receptors (S1PRs). Here, we studied the role of S1PR2 in the regulation of the proadhesion and proinflammatory phenotype of the endothelium. By using genetic approaches and a S1PR2-specific antagonist (JTE013), we found that S1PR2 plays a key role in the permeability and inflammatory responses of the vascular endothelium during endotoxemia. Experiments with bone marrow chimeras (S1pr2(+/+) → S1pr2(+/+), S1pr2(+/+) → S1pr2(-/-), and S1pr2(-/-) → S1pr2(+/+)) indicate the critical role of S1PR2 in the stromal compartment, in the regulation of vascular permeability and vascular inflammation. In vitro, JTE013 potently inhibited tumor necrosis factor α-induced endothelial inflammation. Finally, we provide detailed mechanisms on the downstream signaling of S1PR2 in vascular inflammation that include the activation of the stress-activated protein kinase pathway that, together with the Rho-kinase nuclear factor kappa B pathway (NF-kB), are required for S1PR2-mediated endothelial inflammatory responses. Taken together, our data indicate that S1PR2 is a key regulator of the proinflammatory phenotype of the endothelium and identify S1PR2 as a novel therapeutic target for vascular disorders.

The Relationship of Pressure Ulcers, Race, and Socioeconomic Conditions After Spinal Cord Injury

PubMed Central

Saunders, Lee L; Krause, James S; Peters, Bridget A; Reed, Karla S

2010-01-01

Objective: To identify risks factors associated with pressure ulcers (PrU) after spinal cord injury (SCI) by examining race and indicators of socioeconomic status (measured by income and education). We hypothesize African Americans will have a greater risk for PrUs than whites, but this relationship will be mediated by the 2 socioeconomic status indicators. Design: Cohort study. Setting: A large rehabilitation hospital in the southeastern US. Participants: 1,466 white and African American adults at least 1-year post-traumatic SCI. Outcome Measures: (a) PrUs in the past year, (b) current PrU, (c) surgery to repair a PrU since injury. Results: In preliminary analyses, race was significantly associated with having a current PrU and with having surgery to repair a PrU since injury. In multivariable analyses, the relationships of PrU with having a current PrU and with having surgery to repair a PrU were both mediated by income and education such that the relationships were no longer significant. Lower income was associated with increased odds of each PrU outcome. After controlling for other variables in the model, education was associated with increased odds of having a current PrU. Conclusion: These findings help clarify the relationships between race and socioeconomic status with PrUs after SCI. Specifically, a lack of resources, both financial and educational, is associated with worse PrU outcomes. These results can be used by both providers and policy makers when considering prevention and intervention strategies for PrUs among people with SCI. PMID:21061898

Rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of the novel anticancer agent PR-104 and its major metabolites in human plasma: Application to a pharmacokinetic study.

PubMed

Gu, Yongchuan; Wilson, William R

2009-10-01

PR-104 is a dinitrobenzamide mustard currently in clinical trial as a hypoxia-activated prodrug. It is converted systemically to the corresponding alcohol, PR-104A, which is activated by nitroreduction to the hydroxylamine (PR-104H) and amine (PR-104M). PR-104A is also metabolised to the O-glucuronide (PR-104G), and by oxidative debromoethylation to the semi-mustard PR-104S. We now report a validated ultra-high-pressure liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) method for the determination of these metabolites in human plasma. Plasma proteins were precipitated with acidified methanol and the supernatant diluted into water. Aliquots were analysed by UHPLC-MS/MS using a Zorbax Eclipse XDB-C18 Rapid Resolution HT (50mmx2.1mm, 1.8microm) column and gradient of acetonitrile and 0.01% formic acid with a 6min run time. The method had a linear range of 0.1-50microM for PR-104, PR-104A and PR-104G, 0.05-5microM for PR-104H, 0.025-2.5microM for PR-104M and 0.01-1microM for PR-104S. The intra-day and inter-day precision and accuracy were within 14%. The extraction recovery of all analytes was over 87%. The validated method was illustrated by using it to study the pharmacokinetics of PR-104 and its metabolites in a human patient.

Solar-panel and parasol strategies shape the proteorhodopsin distribution pattern in marine Flavobacteriia.

PubMed

Kumagai, Yohei; Yoshizawa, Susumu; Nakajima, Yu; Watanabe, Mai; Fukunaga, Tsukasa; Ogura, Yoshitoshi; Hayashi, Tetsuya; Oshima, Kenshiro; Hattori, Masahira; Ikeuchi, Masahiko; Kogure, Kazuhiro; DeLong, Edward F; Iwasaki, Wataru

2018-05-01

Proteorhodopsin (PR) is a light-driven proton pump that is found in diverse bacteria and archaea species, and is widespread in marine microbial ecosystems. To date, many studies have suggested the advantage of PR for microorganisms in sunlit environments. The ecophysiological significance of PR is still not fully understood however, including the drivers of PR gene gain, retention, and loss in different marine microbial species. To explore this question we sequenced 21 marine Flavobacteriia genomes of polyphyletic origin, which encompassed both PR-possessing as well as PR-lacking strains. Here, we show that the possession or alternatively the lack of PR genes reflects one of two fundamental adaptive strategies in marine bacteria. Specifically, while PR-possessing bacteria utilize light energy ("solar-panel strategy"), PR-lacking bacteria exclusively possess UV-screening pigment synthesis genes to avoid UV damage and would adapt to microaerobic environment ("parasol strategy"), which also helps explain why PR-possessing bacteria have smaller genomes than those of PR-lacking bacteria. Collectively, our results highlight the different strategies of dealing with light, DNA repair, and oxygen availability that relate to the presence or absence of PR phototrophy.

Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs

PubMed Central

Rouvinski, Alexander; Karniely, Sharon; Kounin, Maria; Moussa, Sanaa; Goldberg, Miri D.; Warburg, Gabriela; Lyakhovetsky, Roman; Papy-Garcia, Dulce; Kutzsche, Janine; Korth, Carsten; Carlson, George A.; Godsave, Susan F.; Peters, Peter J.; Luhr, Katarina; Kristensson, Krister

2014-01-01

Mammalian prions refold host glycosylphosphatidylinositol-anchored PrPC into β-sheet–rich PrPSc. PrPSc is rapidly truncated into a C-terminal PrP27-30 core that is stable for days in endolysosomes. The nature of cell-associated prions, their attachment to membranes and rafts, and their subcellular locations are poorly understood; live prion visualization has not previously been achieved. A key obstacle has been the inaccessibility of PrP27-30 epitopes. We overcame this hurdle by focusing on nascent full-length PrPSc rather than on its truncated PrP27-30 product. We show that N-terminal PrPSc epitopes are exposed in their physiological context and visualize, for the first time, PrPSc in living cells. PrPSc resides for hours in unexpected cell-surface, slow moving strings and webs, sheltered from endocytosis. Prion strings observed by light and scanning electron microscopy were thin, micrometer-long structures. They were firmly cell associated, resisted phosphatidylinositol-specific phospholipase C, aligned with raft markers, fluoresced with thioflavin, and were rapidly abolished by anti-prion glycans. Prion strings and webs are the first demonstration of membrane-anchored PrPSc amyloids. PMID:24493590

Overexpression of NtPR-Q Up-Regulates Multiple Defense-Related Genes in Nicotiana tabacum and Enhances Plant Resistance to Ralstonia solanacearum.

PubMed

Tang, Yuanman; Liu, Qiuping; Liu, Ying; Zhang, Linli; Ding, Wei

2017-01-01

Various classes of plant pathogenesis-related proteins have been identified in the past several decades. PR-Q, a member of the PR3 family encoding chitinases, has played an important role in regulating plant resistance and preventing pathogen infection. In this paper, we functionally characterized NtPR-Q in tobacco plants and found that the overexpression of NtPR-Q in tobacco Yunyan87 resulted in higher resistance to Ralstonia solanacearum inoculation. Surprisingly, overexpression of NtPR-Q led to the activation of many defense-related genes, such as salicylic acid (SA)-responsive genes NtPR1a/c , NtPR2 and NtCHN50 , JA-responsive gene NtPR1b and ET production-associated genes NtACC Oxidase and NtEFE26 . Consistent with the role of NtPR-Q in multiple stress responses, NtPR-Q transcripts were induced by the exogenous hormones SA, ethylene and methyl jasmonate, which could enhance the resistance of tobacco to R. solanacearum . Collectively, our results suggested that NtPR-Q overexpression led to the up-regulation of defense-related genes and enhanced plant resistance to R. solanacearum infection.

Underlying Chronic Disease, Medication Use, History of Running Injuries and Being a More Experienced Runner Are Independent Factors Associated With Exercise-Associated Muscle Cramping: A Cross-Sectional Study in 15778 Distance Runners.

PubMed

Schwellnus, Martin P; Swanevelder, Sonja; Jordaan, Esme; Derman, Wayne; Van Rensburg, Dina C Janse

2018-05-01

Exercise-associated muscle cramping (EAMC) is a significant medical complication in distance runners, yet factors associated with EAMC are poorly documented. To document risk factors associated with EAMC in runners. Cross-sectional study. Two ocean races (21.1 km, and 56 km). Fifteen thousand seven hundred seventy-eight race entrants. Participants completed a prerace medical history screening tool including: training, cardiovascular disease (CVD), risk factors for, and symptoms of CVD, history of diseases affecting major organ systems, cancer, allergies, medication use, and running injury. Runners were grouped as having a history of EAMC (hEAMC group = 2997) and a control group (Control = 12 781). Independent factors associated with a higher prevalence ratio (PR) of hEAMC were any risk factor for CVD (PR = 1.16; P = 0.0002), symptoms of CVD (PR = 2.38; P < 0.0001), respiratory disease (PR = 1.33; P < 0.0001), gastrointestinal disease (PR = 1.86; P < 0.0001), nervous system or psychiatric disease (PR = 1.51; P < 0.0001), kidney or bladder disease, (PR = 1.60; P < 0.0001), haematological or immune disease (PR = 1.54; P = 0.0048), cancer (PR = 1.34; P = 0.0031), allergies (PR = 1.37; P < 0.0001), regular medication use (PR = 1.80; P < 0.0001), statin use (PR = 1.26; P = 0.0127), medication use during racing (PR = 1.88; P < 0.0001), running injury (PR = 1.66; P < 0.0001), muscle injury (PR = 1.82; P < 0.0001), tendon injury (PR = 1.62; P < 0.0001), and runners in the experienced category (PR = 1.22; P < 0.0001). Novel risk factors associated with EAMC in distance runners were underlying chronic disease, medication use, a history of running injuries, and experienced runners. These factors must be identified as possible associations, and therefore be considered in the diagnosis and treatment of EAMC.

Tolerability of a Fully Maturated Cheese in Cow’s Milk Allergic Children: Biochemical, Immunochemical, and Clinical Aspects

PubMed Central

Alessandri, Claudia; Sforza, Stefano; Palazzo, Paola; Lambertini, Francesca; Paolella, Sara; Zennaro, Danila; Rafaiani, Chiara; Ferrara, Rosetta; Bernardi, Maria Livia; Santoro, Mario; Zuzzi, Sara; Giangrieco, Ivana; Dossena, Arnaldo; Mari, Adriano

2012-01-01

Background From patients’ reports and our preliminary observations, a fully maturated cheese (Parmigiano-Reggiano; PR) seems to be well tolerated by a subset of cow’s milk (CM) allergic patients. Objective and Methods To biochemically and immunologically characterize PR samples at different maturation stage and to verify PR tolerability in CM allergic children. Seventy patients, with suspected CM allergy, were enrolled. IgE to CM, α-lactalbumin (ALA), β-lactoglobulin (BLG) and caseins (CAS) were tested using ImmunoCAP, ISAC103 and skin prick test. Patients underwent a double-blind, placebo-controlled food challenge with CM, and an open food challenge with 36 months-maturated PR. Extracts obtained from PR samples were biochemically analyzed in order to determine protein and peptide contents. Pepsin and trypsin-chymotrypsin-pepsin simulated digestions were applied to PR extracts. Each PR extract was investigated by IgE Single Point Highest Inhibition Achievable assay (SPHIAa). The efficiency analysis was carried out using CM and PR oral challenges as gold standards. Results The IgE binding to milk allergens was 100% inhibited by almost all PR preparations; the only difference was for CAS, mainly αS1-CAS. Sixteen patients sensitized to CM tolerated both CM and PR; 29 patients tolerated PR only; 21 patients, reacted to both CM and PR, whereas 4 patients reactive to CM refused to ingest PR. ROC analysis showed that the absence of IgE to BLG measured by ISAC could be a good marker of PR tolerance. The SPHIAa using digested PR preparations showed a marked effect on IgE binding to CAS and almost none on ALA and BLG. Conclusions 58% of patients clinically reactive to CM tolerated fully maturated PR. The preliminary digestion of CAS induced by PR maturation process, facilitating a further loss of allergenic reactivity during gut digestion, might explain the tolerance. This hypothesis seems to work when no IgE sensitization to ISAC BLG is detected. PMID:22829901

Uncovering the defence responses of Eucalyptus to pests and pathogens in the genomics age.

PubMed

Naidoo, Sanushka; Külheim, Carsten; Zwart, Lizahn; Mangwanda, Ronishree; Oates, Caryn N; Visser, Erik A; Wilken, Febé E; Mamni, Thandekile B; Myburg, Alexander A

2014-09-01

Long-lived tree species are subject to attack by various pests and pathogens during their lifetime. This problem is exacerbated by climate change, which may increase the host range for pathogens and extend the period of infestation by pests. Plant defences may involve preformed barriers or induced resistance mechanisms based on recognition of the invader, complex signalling cascades, hormone signalling, activation of transcription factors and production of pathogenesis-related (PR) proteins with direct antimicrobial or anti-insect activity. Trees have evolved some unique defence mechanisms compared with well-studied model plants, which are mostly herbaceous annuals. The genome sequence of Eucalyptus grandis W. Hill ex Maiden has recently become available and provides a resource to extend our understanding of defence in large woody perennials. This review synthesizes existing knowledge of defence mechanisms in model plants and tree species and features mechanisms that may be important for defence in Eucalyptus, such as anatomical variants and the role of chemicals and proteins. Based on the E. grandis genome sequence, we have identified putative PR proteins based on sequence identity to the previously described plant PR proteins. Putative orthologues for PR-1, PR-2, PR-4, PR-5, PR-6, PR-7, PR-8, PR-9, PR-10, PR-12, PR-14, PR-15 and PR-17 have been identified and compared with their orthologues in Populus trichocarpa Torr. & A. Gray ex Hook and Arabidopsis thaliana (L.) Heynh. The survey of PR genes in Eucalyptus provides a first step in identifying defence gene targets that may be employed for protection of the species in future. Genomic resources available for Eucalyptus are discussed and approaches for improving resistance in these hardwood trees, earmarked as a bioenergy source in future, are considered. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biological properties of prolactin-releasing peptide analogs with a modified aromatic ring of a C-terminal phenylalanine amide.

PubMed

Maletínská, Lenka; Spolcová, Andrea; Maixnerová, Jana; Blechová, Miroslava; Zelezná, Blanka

2011-09-01

Prolactin-releasing peptide (PrRP)-induced secretion of prolactin is not currently considered a primary function of PrRP, but the development of late-onset obesity in both PrRP and PrRP receptor knock-out mice indicates the unique anorexigenic properties of PrRP. In our recent study, we showed comparable potencies of peptides PrRP31 and PrRP20 in binding, intracellular signaling and prolactin release in pituitary RC-4B/C cells, and anorexigenic effect after central administration in fasted mice. In the present study, eight analogs of PrRP20 with C-terminal Phe amide modified with a bulky side chain or a halogenated aromatic ring revealed high binding potency, activation of mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK1/2) and cAMP response element-binding protein (CREB) and prolactin release in RC-4B/C cells. In particular, [PheNO(2)(31)]PrRP20, [1-Nal(31)]PrRP20, [2-Nal(31)]PrRP20 and [Tyr(31)]PrRP20 showed not only in vitro effects comparable or higher than those of PrRP20, but also a very significant and long-lasting anorexigenic effect after central administration in fasted mice. The design of potent and long-lasting PrRP analogs with selective anorexigenic properties promises to contribute to the study of food intake disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Accuracy of a third (Dolphin Voyager) versus first generation pulse oximeter (Nellcor N-180) in predicting arterial oxygen saturation and pulse rate in the anesthetized dog.

PubMed

Burns, Patrick M; Driessen, Bernd; Boston, Ray; Gunther, Robert A

2006-09-01

To compare the accuracy of a 3rd (Dolphin Voyager) versus 1st generation pulse oximeter (Nellcor N-180). Prospective laboratory investigation. Eight adult dogs. In anesthetized dogs, arterial oxygen saturation (SpO(2)) was recorded simultaneously with each pulse oximeter. The oxygen fraction in inspired gas (FiO(2)) was successively reduced from 1.00 to 0.09, with re-saturation (FiO(2) 0.40) after each breathe-down step. After each 3-minute FiO(2) plateau, SpO(2) and pulse rate (PR) were compared with the fractional arterial saturation (SaO(2)) and PR determined by co-oximetry and invasive blood pressure monitoring, respectively. Data analysis included Bland-Altman (B-A) plots, Lin's concordance correlation factor (rho(c)), and linear regression models. Over a SaO(2) range of 33-99%, the overall bias (mean SpO(2) - SaO(2)), precision (SD of bias), and accuracy (A(rms)) for the Dolphin Voyager and Nellcor N-180 were 4.3%, 4.4%, and 6.1%, and 3.2%, 3.0%, and 4.3%, respectively. Bias increased at SaO(2) < 90%, more so with the Dolphin Voyager (from 1.6% to 8.6%) than Nellcor N-180 (from 3.2% to 4.5%). The SpO(2) readings correlated significantly with SaO(2) for both the Dolphin Voyager (rho(c) = 0.94) and Nellcor N-180 (rho(c) = 0.97) (p < 0.001). Regarding PR, bias, precision, and accuracy (A(rms)) for the Dolphin Voyager and Nellcor N-180 were -0.5, 4.6, and 4.6 and 1.38, 4.3, and 4.5 beats minute(-1), respectively. Significant correlation existed between pulse oximeter and directly measured PR (Dolphin Voyager: rho(c) = 0.98; Nellcor N-180: rho(c) = 0.99) (p < 0.001). In anesthetized dogs with adequate hemodynamic function, both instruments record SaO(2) relatively accurately over a wide range of normal saturation values. However, there is an increasing overestimation at SaO(2) < 90%, particularly with the Dolphin Voyager, indicating that 3rd generation pulse oximeters may not perform better than older instruments. The 5.4-fold increase in bias with the Dolphin Voyager at SaO(2) < 90% stresses the importance of a 93-94% SpO(2) threshold to ensure an arterial saturation of >or=90%. In contrast, PR monitoring with both devices is very reliable.

Plant Pathogenesis-Related Proteins PR-10 and PR-14 as Components of Innate Immunity System and Ubiquitous Allergens.

PubMed

Finkina, Ekaterina I; Melnikova, Daria N; Bogdanov, Ivan V; Ovchinnikova, Tatiana V

2017-01-01

Pathogenesis-related (PR) proteins are components of innate immunity system in plants. They play an important role in plant defense against pathogens. Lipid transfer proteins (LTPs) and Bet v 1 homologs comprise of two separate families of PR-proteins. Both LTPs (PR-14) and Bet v 1 homologs (PR-10) are multifunctional small proteins involving in plant response to abiotic and biotic stress conditions. The representatives of these PR-protein families do not show any sequence similarity but have other common biochemical features such as low molecular masses, the presence of hydrophobic cavities, ligand binding properties, and antimicrobial activities. Besides, many members of PR-10 and PR-14 families are ubiquitous plant panallergens which are able to cause sensitization of human immune system and crossreactive allergic reactions to plant food and pollen. This review is aimed at comparative analysis of structure-functional and allergenic properties of the PR-10 and PR-14 families, as well as prospects for their medicinal application. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Anomalous pH Effect of Blue Proteorhodopsin.

PubMed

Yamada, Keisuke; Kawanabe, Akira; Yoshizawa, Susumu; Inoue, Kentaro; Kogure, Kazuhiro; Kandori, Hideki

2012-04-05

Proteorhodopsin (PR) is a light-driven proton pump found in marine bacteria, and thousands of PRs are classified into blue-absorbing PR (B-PR; λmax ≈ 490 nm) and green-absorbing PR (G-PR; λmax ≈ 525 nm). In this report, we present conversion of B-PR into G-PR using anomalous pH effect. B-PR in LC1-200, marine γ-proteobacteria, absorbs 497 and 513 nm maximally at pH 7 and 4, respectively, whose pH titration was reversible (pKa = 4.8). When pH was lowered from 4, the λmax was further red-shifted (528 nm at pH 2). This is unusual because blue shift occurs by chloride binding in the case of bacteriorhodopsin. Surprisingly, when pH was increased from 2 to 7, the λmax of this B-PR was further red-shifted to 540 nm, indicating that green-absorbing PR (PR540) is created only by changing pH. The present study reports the conformational flexibility of microbial rhodopsins, leading to the switch of absorbing color by a simple pH change.

Aminotroponiminate calcium and strontium complexes.

PubMed

Datta, Simmi; Gamer, Michael T; Roesky, Peter W

2008-06-07

Heteroleptic aminotroponiminate complexes of calcium and strontium have been prepared. The monomeric calcium complex [((iPr)2ATI)CaI(THF)3] 1 ((iPr)2ATI = N-isopropyl-2-(isopropylamino)troponiminate) and the corresponding dimeric strontium compound [( (iPr)2ATI)SrI(THF)2]2 2 were obtained by reaction of [((iPr)2ATI)K] and MI2. Whereas the mixed ligand compound of composition [((iPr)2ATI)Ca(iPrAT)]2 3 (iPrAT = 2-(isopropylamino)troponate) was not obtained via a salt metathesis but by reaction of [Ca(N(SiMe3)2)2(THF)2] with ( (iPr)2ATI)H and (iPrAT)H, the diphosphanylamido complex [( (iPr)2ATI)Ca((Ph2P)2N)(THF)2] was obtained by reaction of CaI2 with the potassium compounds [( (iPr)2ATI)K] and [K(THF)n][N(PPh2)2]. The single crystal X-ray structures of all compounds were established and the latter compound shows a eta2-coordination mode of the ligand via the nitrogen and one phosphorus atom.

C-Terminal Helical Domains of Dengue Virus Type 4 E Protein Affect the Expression/Stability of prM Protein and Conformation of prM and E Proteins

PubMed Central

Tsai, Wen-Yang; Hsieh, Szu-Chia; Lai, Chih-Yun; Lin, Hong-En; Nerurkar, Vivek R.; Wang, Wei-Kung

2012-01-01

Background The envelope (E) protein of dengue virus (DENV) is the major immunogen for dengue vaccine development. At the C-terminus are two α-helices (EH1 and EH2) and two transmembrane domains (ET1 and ET2). After synthesis, E protein forms a heterodimer with the precursor membrane (prM) protein, which has been shown as a chaperone for E protein and could prevent premature fusion of E protein during maturation. Recent reports of enhancement of DENV infectivity by anti-prM monoclonal antibodies (mAbs) suggest the presence of prM protein in dengue vaccine is potentially harmful. A better understanding of prM-E interaction and its effect on recognition of E and prM proteins by different antibodies would provide important information for future design of safe and effective subunit dengue vaccines. Methodology/Principal Findings In this study, we examined a series of C-terminal truncation constructs of DENV4 prME, E and prM. In the absence of E protein, prM protein expressed poorly. In the presence of E protein, the expression of prM protein increased in a dose-dependent manner. Radioimmunoprecipitation, sucrose gradient sedimentation and pulse-chase experiments revealed ET1 and EH2 were involved in prM-E interaction and EH2 in maintaining the stability of prM protein. Dot blot assay revealed E protein affected the recognition of prM protein by an anti-prM mAb; truncation of EH2 or EH1 affected the recognition of E protein by several anti-E mAbs, which was further verified by capture ELISA. The E protein ectodomain alone can be recognized well by all anti-E mAbs tested. Conclusions/Significance A C-terminal domain (EH2) of DENV E protein can affect the expression and stability of its chaperone prM protein. These findings not only add to our understanding of the interaction between prM and E proteins, but also suggest the ectodomain of E protein alone could be a potential subunit immunogen without inducing anti-prM response. PMID:23300717

A thermal and chemical degradation approach to decipher pristane and phytane precursors in sedimentary organic matter

USGS Publications Warehouse

Koopmans, M.P.; Rijpstra, W.I.C.; Klapwijk, M.M.; De Leeuw, J. W.; Lewan, M.D.; Sinninghe, Damste J.S.

1999-01-01

A thermal and chemical degradation approach was followed to determine the precursors of pristane (Pr) and phytane (Ph) in samples from the Gessoso-solfifera, Ghareb and Green River Formations. Hydrous pyrolysis of these samples yields large amounts of Pr and Ph carbon skeletons, indicating that their precursors are predominantly sequestered in high-molecular-weight fractions. However, chemical degradation of the polar fraction and the kerogen of the unheated samples generally does not release large amounts of Pr and Ph. Additional information on the precursors of Pr and Ph is obtained from flash pyrolysis analyses of kerogens and residues after hydrous pyrolysis and after chemical degradation. Multiple precursors for Pr and Ph are recognised in these three samples. The main increase of the Pr/Ph ratio with increasing maturation temperature, which is associated with strongly increasing amounts of Pr and Ph, is probably due to the higher amount of precursors of Pr compared to Ph, and not to the different timing of generation of Pr and Ph.A thermal and chemical degradation approach was followed to determine the precursors of pristane (Pr) and phytane (Ph) in samples from the Gessoso-solfifera, Ghareb and Green River Formations. Hydrous pyrolysis of these samples yields large amounts of Pr and Ph carbon skeletons, indicating that their precursors are predominantly sequestered in high-molecular-weight fractions. However, chemical degradation of the polar fraction and the kerogen of the unheated samples generally does not release large amounts of Pr and Ph. Additional information on the precursors of Pr and Ph is obtained from flash pyrolysis analyses of kerogens and residues after hydrous pyrolysis and after chemical degradation. Multiple precursors for Pr and Ph are recognised in these three samples. The main increase of the Pr/Ph ratio with increasing maturation temperature, which is associated with strongly increasing amounts of Pr and Ph, is probably due to the higher amount of precursors of Pr compared to Ph, and not to the different timing of generation of Pr and Ph.

Prion protein modulates glucose homeostasis by altering intracellular iron.

PubMed

Ashok, Ajay; Singh, Neena

2018-04-26

The prion protein (PrP C ), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP -/- ) were significantly lower than wild type (PrP +/+ ) controls. Silencing of PrP C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP C -dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP +/+ but not PrP -/- mice, indicating PrP C -mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP +/+ relative to PrP -/- mice, suggesting that PrP C -mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer's disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.

Structure of glycosylated and unglycosylated gag polyproteins of Rauscher murine leukemia virus: carbohydrate attachment sites.

PubMed Central

Schultz, A M; Lockhart, S M; Rabin, E M; Oroszlan, S

1981-01-01

The structural relationships among the gag polyproteins Pr65gag, Pr75gag, and gPr80gag of Rauscher murine leukemia virus were studied by endoglycosidase H digestion and formic acid cleavage. Fragments were identified by precipitation with specific antisera to constituent virion structural proteins followed by one-dimensional mapping. Endoglycosidase H reduced the size of gPr80gag to that of Pr75gag. By comparing fragments of gPr80gag and the apoprotein Pr75gag, the former was shown to contain two mannose-rich oligosaccharide units. By comparing fragments of Pr65gag and Pr75gag, the latter was shown to differ from Pr65gag at the amino terminus by the presence of a leader peptide approximately 7,000 daltons in size. The internal and carboxyl-terminal peptides of the two unglycosylated polyproteins were not detectably different. The location of the two N-linked carbohydrate chains in gPr80gag has been specified. One occurs in the carboxyl-terminal half of the polyprotein at asparagine177 of the p30 sequence and the other is found in a 23,000-dalton fragment located in the amino-terminal region of gPr80gag and containing the additional amino acid sequences not found in Pr65gag plus a substantial portion of p15. Images PMID:7241663

Solubility and cation exchange in phosphate rock and saturated clinoptilolite mixtures

NASA Technical Reports Server (NTRS)

Allen, E. R.; Hossner, L. R.; Ming, D. W.; Henninger, D. L.

1993-01-01

Mixtures of zeolite and phosphate rock (PR) have the potential to provide slow-release fertilization of plants in synthetic soils by dissolution and ion-exchange reactions. This study was conducted to examine solubility and cation-exchange relationships in mixtures of PR and NH4- and K-saturated clinoptilolite (Cp). Batch-equilibration experiments were designed to investigate the effect of PR source, the proportion of exchangeable K and NH4, and the Cp to PR ratio on solution N, P, K, and Ca concentrations. The dissolution and cation-exchange reactions that occurred after mixing NH4- and K-saturated Cp with PR increased the solubility of the PR and simultaneously released NH4 and K into solution. The more reactive North Carolina (NC) PR rendered higher solution concentrations of NH4 and K when mixed with Cp than did Tennessee (TN) PR. Solution P concentrations for the Cp-NC PR mixture and the Cp-TN PR mixture were similar. Solution concentrations of N, P, K, and Ca and the ratios of these nutrients in solution varied predictably with the type of PR, the Cp/PR ratio, and the proportions of exchangeable K and NH4 on the Cp. Our research indicated that slow-release fertilization using Cp/PR media may provide adequate levels of N, P, and K to support plant growth. Solution Ca concentrations were lower than optimum for plant growth.

Prion Protein Promotes Kidney Iron Uptake via Its Ferrireductase Activity*

PubMed Central

Haldar, Swati; Tripathi, Ajai; Qian, Juan; Beserra, Amber; Suda, Srinivas; McElwee, Matthew; Turner, Jerrold; Hopfer, Ulrich; Singh, Neena

2015-01-01

Brain iron-dyshomeostasis is an important cause of neurotoxicity in prion disorders, a group of neurodegenerative conditions associated with the conversion of prion protein (PrPC) from its normal conformation to an aggregated, PrP-scrapie (PrPSc) isoform. Alteration of iron homeostasis is believed to result from impaired function of PrPC in neuronal iron uptake via its ferrireductase activity. However, unequivocal evidence supporting the ferrireductase activity of PrPC is lacking. Kidney provides a relevant model for this evaluation because PrPC is expressed in the kidney, and ∼370 μg of iron are reabsorbed daily from the glomerular filtrate by kidney proximal tubule cells (PT), requiring ferrireductase activity. Here, we report that PrPC promotes the uptake of transferrin (Tf) and non-Tf-bound iron (NTBI) by the kidney in vivo and mainly NTBI by PT cells in vitro. Thus, uptake of 59Fe administered by gastric gavage, intravenously, or intraperitoneally was significantly lower in PrP-knock-out (PrP−/−) mouse kidney relative to PrP+/+ controls. Selective in vivo radiolabeling of plasma NTBI with 59Fe revealed similar results. Expression of exogenous PrPC in immortalized PT cells showed localization on the plasma membrane and intracellular vesicles and increased transepithelial transport of 59Fe-NTBI and to a smaller extent 59Fe-Tf from the apical to the basolateral domain. Notably, the ferrireductase-deficient mutant of PrP (PrPΔ51–89) lacked this activity. Furthermore, excess NTBI and hemin caused aggregation of PrPC to a detergent-insoluble form, limiting iron uptake. Together, these observations suggest that PrPC promotes retrieval of iron from the glomerular filtrate via its ferrireductase activity and modulates kidney iron metabolism. PMID:25572394

Prion Protein Regulates Iron Transport by Functioning as a Ferrireductase

PubMed Central

Singh, Ajay; Haldar, Swati; Horback, Katharine; Tom, Cynthia; Zhou, Lan; Meyerson, Howard; Singh, Neena

2017-01-01

Prion protein (PrPC) is implicated in the pathogenesis of prion disorders, but its normal function is unclear. We demonstrate that PrPC is a ferrireductase (FR), and its absence causes systemic iron deficiency in PrP knock-out mice (PrP−/−). When exposed to non-transferrin-bound (NTB) radioactive-iron (59FeCl3) by gastric-gavage, PrP−/− mice absorb significantly more 59Fe from the intestinal lumen relative to controls, indicating appropriate systemic response to the iron deficiency. Chronic exposure to excess dietary iron corrects this deficiency, but unlike wild-type (PrP+/+) controls that remain iron over-loaded, PrP−/− mice revert back to the iron deficient phenotype after 5 months of chase on normal diet. Bone marrow (BM) preparations of PrP−/− mice on normal diet show relatively less stainable iron, and this phenotype is only partially corrected by intraperitoneal administration of excess iron-dextran. Cultured PrP−/− BM-macrophages incorporate significantly less NTB-59Fe in the absence or presence of excess extracellular iron, indicating reduced uptake and/or storage of available iron in the absence of PrPC. When expressed in neuroblastoma cells, PrPC exhibits NAD(P)H-dependent cell-surface and intracellular FR activity that requires the copper-binding octa-peptide-repeat region and linkage to the plasma membrane for optimal function. Incorporation of NTB-59Fe by neuroblastoma cells correlates with FR activity of PrPC, implicating PrPC in cellular iron uptake and metabolism. These observations explain the correlation between PrPC expression and cellular iron levels, and the cause of iron imbalance in sporadic-Creutzfeldt-Jakob-disease brains where PrPC accumulates as insoluble aggregates. PMID:23478311

S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis.

PubMed

Hou, JinChao; Chen, QiXing; Wu, XiaoLiang; Zhao, DongYan; Reuveni, Hadas; Licht, Tamar; Xu, MengLong; Hu, Hu; Hoeft, Andreas; Ben-Sasson, Shmuel A; Shu, Qiang; Fang, XiangMing

2017-12-15

Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown. To investigate the role of S1PR3 in antibacterial immunity during sepsis. Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers. S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3 -/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3 -/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3 -/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes. S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.

The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV

PubMed Central

Waddington, Lynne; Hijnen, Marcel; Velkov, Tony; McKinstry, William J.

2017-01-01

The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packaging are essential elements that facilitate HIV assembly. However, mechanistic details of these interactions are not clearly defined. Here, we overcome previous limitations in producing large quantities of full-length recombinant Pr55Gag that is required for isothermal titration calorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIV assembly for the first time. Thermodynamic analysis showed that the binding between RNA and HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced by the oligomerization of Pr55Gag. The change in enthalpy (ΔH) widens sequentially from: (1) Pr55Gag-Psi RNA binding during HIV genome selection; to (2) Pr55Gag-Guanosine Uridine (GU)-containing RNA binding in cytoplasm/plasma membrane; and then to (3) Pr55Gag-Adenosine(A)-containing RNA binding in immature HIV. These data imply the stepwise increments of heat being released during HIV biogenesis may help to facilitate the process of viral assembly. By mimicking the interactions between A-containing RNA and oligomeric Pr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficient than full-length Pr55Gag in this thermodynamic process. These data suggest a potential unknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction during HIV assembly. Our data provide direct evidence on how nucleic acid sequences and the oligomeric state of Pr55Gag regulate HIV assembly. PMID:28222188

Social, structural, behavioral and clinical factors influencing retention in Pre-Exposure Prophylaxis (PrEP) care in Mississippi.

PubMed

Arnold, Trisha; Brinkley-Rubinstein, Lauren; Chan, Philip A; Perez-Brumer, Amaya; Bologna, Estefany S; Beauchamps, Laura; Johnson, Kendra; Mena, Leandro; Nunn, Amy

2017-01-01

Pre-exposure prophylaxis (PrEP) is a biomedical intervention that can reduce rates of HIV transmission when taken once daily by HIV-negative individuals. Little is understood about PrEP uptake and retention in care among the populations most heavily impacted by the HIV epidemic, particularly among young men who have sex with men (YMSM) in the Deep South. Therefore, this study explored the structural, social, behavioral, and clinical factors that affect PrEP use and retention in care among YMSM in Jackson, Mississippi. Thirty MSM who were prescribed PrEP at an outpatient primary care clinic were interviewed and included 23 men who had been retained in PrEP care and seven who had not been retained. The mean age of participants was 26.6 years. Most (23) participants were African American. Major factors affecting PrEP use and retention in PrEP care included 1) structural factors such as cost and access to financial assistance for medications and clinical services; 2) social factors such as stigma and relationship status; 3) behavioral factors including sexual risk behaviors; and 4) clinical factors such as perceived and actual side effects. Many participants also discussed the positive spillover effects of PrEP use and reported that PrEP had a positive impact on their health. Four of the seven individuals who had not been retained re-enrolled in PrEP care after completing their interviews, suggesting that case management and ongoing outreach can enhance retention in PrEP care. Interventions to enhance retention in PrEP care among MSM in the Deep South will be most effective if they address the complex structural, social, clinical, and behavioral factors that influence PrEP uptake and retention in PrEP care.

HIV Care Providers' Intentions to Prescribe and Actual Prescription of Pre-Exposure Prophylaxis to At-Risk Adolescents and Adults.

PubMed

Mullins, Tanya L Kowalczyk; Zimet, Gregory; Lally, Michelle; Xu, Jiahong; Thornton, Sarah; Kahn, Jessica A

2017-12-01

Pre-exposure prophylaxis (PrEP) is indicated for use in US adults, and little is known about clinician intentions to prescribe and actual prescription of PrEP to adolescents younger than 18. Fifty-six clinicians who care for HIV-infected and at-risk youth completed an anonymous online survey in 2014. Primary outcomes were (1) intentions to prescribe PrEP to adolescents and adults in four risk categories [men who have sex with men (MSM), transgender women, heterosexuals with multiple partners of unknown HIV status, heterosexuals with HIV-infected partners]; and (2) actual prescription of PrEP to adolescents and adults in these risk groups. Independent variables included clinician characteristics, experience prescribing nonoccupational postexposure prophylaxis, familiarity with and knowledge of PrEP and PrEP guidance, attitudes toward PrEP, and facilitating factors for prescribing PrEP and incorporation of PrEP guidance into practice. Variables associated with intention to prescribe ("very likely to prescribe" vs. other responses) and actual prescription of PrEP stratified by age and risk category were identified in logistic regression models. Mean age was 45.9 years (standard deviation 10.7); 64% were physicians. More clinicians reported high intention to prescribe PrEP to adult versus adolescent MSM (p = 0.02) and transgender women (p = 0.001). Variables associated with intention to prescribe and prescription of PrEP differed by age and risk category. In adolescents, those variables included positive beliefs, higher number of facilitating factors, and fewer barriers to PrEP prescription. Designing strategies based on these findings that address both facilitating factors and barriers to PrEP prescription may improve PrEP uptake by at-risk youth.

Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling

PubMed Central

Singhal, Hari; Greene, Marianne E.; Zarnke, Allison L.; Laine, Muriel; Al Abosy, Rose; Chang, Ya-Fang; Dembo, Anna G.; Schoenfelt, Kelly; Vadhi, Raga; Qiu, Xintao; Rao, Prakash; Santhamma, Bindu; Nair, Hareesh B.; Nickisch, Klaus J.; Long, Henry W.; Becker, Lev; Brown, Myles; Greene, Geoffrey L.

2018-01-01

Major roadblocks to developing effective progesterone receptor (PR)-targeted therapies in breast cancer include the lack of highly-specific PR modulators, a poor understanding of the pro- or anti-tumorigenic networks for PR isoforms and ligands, and an incomplete understanding of the cross talk between PR and estrogen receptor (ER) signaling. Through genomic analyses of xenografts treated with various clinically-relevant ER and PR-targeting drugs, we describe how the activation or inhibition of PR differentially reprograms estrogen signaling, resulting in the segregation of transcriptomes into separate PR agonist and antagonist-mediated groups. These findings address an ongoing controversy regarding the clinical utility of PR agonists and antagonists, alone or in combination with tamoxifen, for breast cancer management. Additionally, the two PR isoforms PRA and PRB, bind distinct but overlapping genomic sites and interact with different sets of co-regulators to differentially modulate estrogen signaling to be either pro- or anti-tumorigenic. Of the two isoforms, PRA inhibited gene expression and ER chromatin binding significantly more than PRB. Differential gene expression was observed in PRA and PRB-rich patient tumors and PRA-rich gene signatures had poorer survival outcomes. In support of antiprogestin responsiveness of PRA-rich tumors, gene signatures associated with PR antagonists, but not PR agonists, predicted better survival outcomes. The better patient survival associated with PR antagonists versus PR agonists treatments was further reflected in the higher in vivo anti-tumor activity of therapies that combine tamoxifen with PR antagonists and modulators. This study suggests that distinguishing common effects observed due to concomitant interaction of another receptor with its ligand (agonist or antagonist), from unique isoform and ligand-specific effects will inform the development of biomarkers for patient selection and translation of PR-targeted therapies to the clinic. PMID:29435103

Phase diagram and equation of state of praseodymium at high pressures and temperatures

NASA Astrophysics Data System (ADS)

Baer, Bruce J.; Cynn, Hyunchae; Iota, Valentin; Yoo, Choong-Shik; Shen, Guoyin

2003-04-01

The phase diagram for praseodymium (Pr) has been determined for pressures between 5 and 60 GPa and temperatures between 295 and 830 K using both in situ energy- and angle-dispersive x-ray diffraction with externally heated diamond-anvil cells. Mineral oil and argon were alternatively used as pressure media in order to compare conflicting results in the literature and to ensure the validity of mineral oil as an inert medium. Evidence for the presence of an, as yet, unidentified phase (denoted Pr-VI) above 675 K has been observed, whereas no compelling evidence has been observed for the existence of the recently reported monoclinic phase (Pr-V). The new constraints of the phase diagram, therefore, suggest that the phase transitions occur as Pr-I(dhcp)→Pr-II(fcc)→Pr-VI→Pr-IV(α-U) above approximately 700 K. Additionally, there is a Pr-III(distorted fcc), Pr-VI, and Pr-IV triple point at approximately 675 K and 23.8 GPa. Temperature-dependent equations of state have been determined, allowing the temperature-dependent volume collapse at the transition between Pr-III and Pr-IV to be calculated. We report a linear decrease of the volume collapse along the Pr-III to Pr-IV boundary with temperature, ΔV/V (%)=16.235-0.0156[T(K)]; the extrapolation indicates that the volume collapse should vanish well below the melting point. With the temperature-dependent equation of state data and new phase diagram we demonstrate that the volume collapse can be accounted for by a change in the multiplicity of Pr atoms as the f electrons go from localized to itinerant.

"I Did Not Want to Give Birth to a Child Who has HIV": Experiences Using PrEP During Pregnancy Among HIV-Uninfected Kenyan Women in HIV-Serodiscordant Couples.

PubMed

Pintye, Jillian; Beima-Sofie, Kristin M; Kimemia, Grace; Ngure, Kenneth; Trinidad, Susan Brown; Heffron, Renee A; Baeten, Jared M; Odoyo, Josephine; Mugo, Nelly; Bukusi, Elizabeth A; Kelley, Maureen C; John-Stewart, Grace C

2017-11-01

The perceptions, motivations, and beliefs of HIV-uninfected women about pre-exposure prophylaxis (PrEP) use during pregnancy can influence its uptake and adherence. This study elicited the views of HIV-uninfected women with personal experience taking PrEP during pregnancy. Qualitative interviews were conducted with HIV-uninfected women who had personal experience taking PrEP while pregnant. Semistructured interviews were conducted with 21 HIV-uninfected Kenyan women in HIV-serodiscordant couples enrolled in an open-label PrEP demonstration project who became pregnant while using PrEP and continued PrEP through their pregnancy. Interviews were audio-recorded and transcribed into English. A qualitative descriptive analysis was performed, using a constant comparison approach to identify key themes related to PrEP use in pregnancy. Desire to remain HIV uninfected and have an HIV-free infant were strong motivators influencing continued use of PrEP during pregnancy. Supporting HIV-infected partners and childbearing within an HIV-serodiscordant relationship were also motivators. Women had challenges distinguishing normal pregnancy symptoms from PrEP side effects and were concerned that observed side effects could be signs of danger for the infant related to PrEP exposure. Health care providers were important conduits of knowledge about PrEP, and continuity of PrEP providers throughout pregnancy facilitated adherence. HIV-uninfected women in HIV-serodiscordant couples were motivated to use PrEP during pregnancy to remain HIV uninfected and to have an HIV-free child but had concerns about side effects. Health care providers will be important for PrEP messaging and adherence support in this unique population.

Electro-optic modulator material

DOEpatents

Adams, John J.; Ebbers, Chris A.

2005-02-22

An electro-optic device for use with a laser beam. A crystal has a first face and a second face. Means are provided for applying a voltage across the crystal to obtain a net phase retardation on the polarization of the laser beam when the laser beam is passed through the crystal. In one embodiment the crystal is composed of a compound having the chemical formula ReAe40(BO3)3 where: RE consists of one or more of the following elements La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu and two other elements Y and Sc; and where Ae is from the list of Ca, Sr, or Ba.

Five-year Experience with Perma Facial Implant

PubMed Central

Raphael, Peter; Harris, Ryan

2014-01-01

Summary: Augmentation cheiloplasty is becoming an increasingly popular aesthetic procedure despite current methodologies having met with disappointment among surgeons and patients. The goal of this study was to examine the benefits and drawbacks of 1 device in particular—Perma Facial Implant (PFI). The senior authors (P.R. and S.W.H.) performed 832 consecutive PFI lip augmentations with excellent results based on photographic documentation, patient satisfaction surveys, unbiased surgeon ratings, and low complication rates. In addition to augmenting thin lips, PFIs hide excess dentition and improve vermilion rhytids and pout. Contrary to alternatives, they are both permanent and reversible. However, they do not level out asymmetries or benefit razor-thin lips without prior lifting or mucosal advancement. PMID:25289346

Impact of insurance coverage on utilization of pre-exposure prophylaxis for HIV prevention.

PubMed

Patel, Rupa R; Mena, Leandro; Nunn, Amy; McBride, Timothy; Harrison, Laura C; Oldenburg, Catherine E; Liu, Jingxia; Mayer, Kenneth H; Chan, Philip A

2017-01-01

Pre-exposure prophylaxis (PrEP) can reduce U.S. HIV incidence. We assessed insurance coverage and its association with PrEP utilization. We reviewed patient data at three PrEP clinics (Jackson, Mississippi; St. Louis, Missouri; Providence, Rhode Island) from 2014-2015. The outcome, PrEP utilization, was defined as patient PrEP use at three months. Multivariable logistic regression was performed to determine the association between insurance coverage and PrEP utilization. Of 201 patients (Jackson: 34%; St. Louis: 28%; Providence: 28%), 91% were male, 51% were White, median age was 29 years, and 21% were uninsured; 82% of patients reported taking PrEP at three months. Insurance coverage was significantly associated with PrEP utilization. After adjusting for Medicaid-expansion and individual socio-demographics, insured patients were four times as likely to use PrEP services compared to the uninsured (OR: 4.49, 95% CI: 1.68-12.01; p = 0.003). Disparities in insurance coverage are important considerations in implementation programs and may impede PrEP utilization.

Differing specificities and isotypes of anti-citrullinated peptide/protein antibodies in palindromic rheumatism and rheumatoid arthritis.

PubMed

Cabrera-Villalba, Sonia; Gomara, María José; Cañete, Juan D; Ramírez, Julio; Salvador, Georgina; Ruiz-Esquide, Virginia; Hernández, Maria Victoria; Inciarte-Mundo, José; Haro, Isabel; Sanmartí, Raimon

2017-06-15

To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA). ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA. CCP2 tested positive in 66.7% of patients with PR and RA. The ACPA distribution of fine specificities and isotypes differed between PR and RA patients. PR patients had a lower frequency of fine ACPA specificities than RA patients, which was significant in the case of a peptide derived from vimentin (PR 24.1% vs. 59.3% RA; p < 0.001). The mean number of ACPA specificities was lower in PR than in RA patients, and only 25.9% of PR patients recognized ≥2 additional specificities compared with 46.3% of RA patients. Significantly less isotype usage, especially IgA, was observed in PR patients. The ACPA immune response differed in patients with PR and RA, with fewer fine specificities and isotype usage in patients with PR. Some patients with PR may have impaired maturation of the B-cell response against citrullinated peptides with no progression to RA.

Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines

PubMed Central

Caughey, Winslow S.; Raymond, Lynne D.; Horiuchi, Motohiro; Caughey, Byron

1998-01-01

A central aspect of pathogenesis in the transmissible spongiform encephalopathies or prion diseases is the conversion of normal protease-sensitive prion protein (PrP-sen) to the abnormal protease-resistant form, PrP-res. Here we identify porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most potent of these tetrapyrroles had IC50 values of 0.5–1 μM in scrapie-infected mouse neuroblastoma (ScNB) cell cultures. Inhibition was observed without effects on protein biosynthesis in general or PrP-sen biosynthesis in particular. Tetrapyrroles also inhibited PrP-res formation in a cell-free reaction composed predominantly of hamster PrP-res and PrP-sen. Inhibitors were found among phthalocyanines, deuteroporphyrins IX, and meso-substituted porphines; examples included compounds containing anionic, neutral protic, and cationic peripheral substituents and various metals. We conclude that certain tetrapyrroles specifically inhibit the conversion of PrP-sen to PrP-res without apparent cytotoxic effects. The inhibition observed in the cell-free conversion reaction suggests that the mechanism involved direct interactions of the tetrapyrrole with PrP-res and/or PrP-sen. These findings introduce a new class of inhibitors of PrP-res formation that represents a potential source of therapeutic agents for transmissible spongiform encephalopathies. PMID:9770449

The Role of Social Relationships in PrEP Uptake and Use Among Transgender Women and Men Who Have Sex with Men.

PubMed

Mehrotra, Megha L; Rivet Amico, K; McMahan, Vanessa; Glidden, David V; Defechereux, Patricia; Guanira, Juan V; Grant, Robert M

2018-05-12

Qualitative studies suggest that social relationships play an important role in HIV pre-exposure prophylaxis (PrEP) use, but there have been few quantitative assessments of the role of social relationships in PrEP uptake or adherence. We examined the association between disclosure of study participation or LGBT identity and PrEP use in the 1603 HIV-negative participants enrolled in the iPrEx OLE study. We also evaluated the association between LGBT social group involvement and PrEP use. Study participation disclosure to parents and LGBT identity disclosure to anyone in a participant's social network were associated with greater PrEP uptake. Study participation disclosure to partners was associated with higher probability of having protective PrEP drug concentrations compared [risk difference 0.15 95% CI (0.01, 0.30)]. For each additional type of LGBT organization a participant was involved in, the probability of PrEP uptake and having protective drug concentrations increased by 0.04 [95% CI (0.03, 0.06)] and 0.04 (95% CI (0.02, 0.07)] respectively. Overall, social context was associated with PrEP use in iPrEx OLE, and should be taken into consideration when designing future PrEP implementation programs.

ck2-dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B isoform-specific target gene expression in breast cancer cells.

PubMed

Hagan, Christy R; Regan, Tarah M; Dressing, Gwen E; Lange, Carol A

2011-06-01

Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin-induced rapid activation of cytoplasmic protein kinases leads to selective regulation of growth-promoting genes by phospho-PR species. Herein, we show that phosphorylation of PR Ser81 is ck2 dependent and progestin regulated in intact cells but also occurs in the absence of PR ligands when cells enter the G(1)/S phase of the cell cycle. T47D breast cancer cells stably expressing a PR-B mutant receptor that cannot be phosphorylated at Ser79/81 (S79/81A) formed fewer soft agar colonies. Regulation of selected genes by PR-B, but not PR-A, also required Ser79/81 phosphorylation for basal and/or progestin-regulated (BIRC3, HSD11β2, and HbEGF) expression. Additionally, wild-type (wt) PR-B, but not S79/81A mutant PR, was robustly recruited to a progesterone response element (PRE)-containing transcriptional enhancer region of BIRC3; abundant ck2 also associated with this region in cells expressing wt but not S79/81A PR. We conclude that phospho-Ser81 PR provides a platform for ck2 recruitment and regulation of selected PR-B target genes. Understanding how ligand-independent PRs function in the context of high levels of kinase activities characteristic of breast cancer is critical to understanding the basis of tumor-specific changes in gene expression and will speed the development of highly selective treatments.

ck2-Dependent Phosphorylation of Progesterone Receptors (PR) on Ser81 Regulates PR-B Isoform-Specific Target Gene Expression in Breast Cancer Cells ▿

PubMed Central

Hagan, Christy R.; Regan, Tarah M.; Dressing, Gwen E.; Lange, Carol A.

2011-01-01

Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin-induced rapid activation of cytoplasmic protein kinases leads to selective regulation of growth-promoting genes by phospho-PR species. Herein, we show that phosphorylation of PR Ser81 is ck2 dependent and progestin regulated in intact cells but also occurs in the absence of PR ligands when cells enter the G1/S phase of the cell cycle. T47D breast cancer cells stably expressing a PR-B mutant receptor that cannot be phosphorylated at Ser79/81 (S79/81A) formed fewer soft agar colonies. Regulation of selected genes by PR-B, but not PR-A, also required Ser79/81 phosphorylation for basal and/or progestin-regulated (BIRC3, HSD11β2, and HbEGF) expression. Additionally, wild-type (wt) PR-B, but not S79/81A mutant PR, was robustly recruited to a progesterone response element (PRE)-containing transcriptional enhancer region of BIRC3; abundant ck2 also associated with this region in cells expressing wt but not S79/81A PR. We conclude that phospho-Ser81 PR provides a platform for ck2 recruitment and regulation of selected PR-B target genes. Understanding how ligand-independent PRs function in the context of high levels of kinase activities characteristic of breast cancer is critical to understanding the basis of tumor-specific changes in gene expression and will speed the development of highly selective treatments. PMID:21518957

Dominant-Negative Inhibition of Prion Formation Diminished by Deletion Mutagenesis of the Prion Protein

PubMed Central

Zulianello, Laurence; Kaneko, Kiyotoshi; Scott, Michael; Erpel, Susanne; Han, Dong; Cohen, Fred E.; Prusiner, Stanley B.

2000-01-01

Polymorphic basic residues near the C terminus of the prion protein (PrP) in humans and sheep appear to protect against prion disease. In heterozygotes, inhibition of prion formation appears to be dominant negative and has been simulated in cultured cells persistently infected with scrapie prions. The results of nuclear magnetic resonance and mutagenesis studies indicate that specific substitutions at the C-terminal residues 167, 171, 214, and 218 of PrPC act as dominant-negative, inhibitors of PrPSc formation (K. Kaneko et al., Proc. Natl. Acad. Sci. USA 94:10069–10074, 1997). Trafficking of substituted PrPC to caveaola-like domains or rafts by the glycolipid anchor was required for the dominant-negative phenotype; interestingly, amino acid replacements at multiple sites were less effective than single-residue substitutions. To elucidate which domains of PrPC are responsible for dominant-negative inhibition of PrPSc formation, we analyzed whether N-terminally truncated PrP(Q218K) molecules exhibited dominant-negative effects in the conversion of full-length PrPC to PrPSc. We found that the C-terminal domain of PrP is not sufficient to impede the conversion of the full-length PrPC molecule and that N-terminally truncated molecules (with residues 23 to 88 and 23 to 120 deleted) have reduced dominant-negative activity. Whether the N-terminal region of PrP acts by stabilizing the C-terminal domain of the molecule or by modulating the binding of PrPC to an auxiliary molecule that participates in PrPSc formation remains to be established. PMID:10756050

HIV-1 Protease in the Fission Yeast Schizosaccharomyces pombe.

PubMed

Benko, Zsigmond; Elder, Robert T; Li, Ge; Liang, Dong; Zhao, Richard Y

2016-01-01

HIV-1 protease (PR) is an essential viral enzyme. Its primary function is to proteolyze the viral Gag-Pol polyprotein for production of viral enzymes and structural proteins and for maturation of infectious viral particles. Increasing evidence suggests that PR cleaves host cellular proteins. However, the nature of PR-host cellular protein interactions is elusive. This study aimed to develop a fission yeast (Schizosaccharomyces pombe) model system and to examine the possible interaction of HIV-1 PR with cellular proteins and its potential impact on cell proliferation and viability. A fission yeast strain RE294 was created that carried a single integrated copy of the PR gene in its chromosome. The PR gene was expressed using an inducible nmt1 promoter so that PR-specific effects could be measured. HIV-1 PR from this system cleaved the same indigenous viral p6/MA protein substrate as it does in natural HIV-1 infections. HIV-1 PR expression in fission yeast cells prevented cell proliferation and induced cellular oxidative stress and changes in mitochondrial morphology that led to cell death. Both these PR activities can be prevented by a PR-specific enzymatic inhibitor, indinavir, suggesting that PR-mediated proteolytic activities and cytotoxic effects resulted from enzymatic activities of HIV-1 PR. Through genome-wide screening, a serine/threonine kinase, Hhp2, was identified that suppresses HIV-1 PR-induced protease cleavage and cell death in fission yeast and in mammalian cells, where it prevented PR-induced apoptosis and cleavage of caspase-3 and caspase-8. This is the first report to show that HIV-1 protease is functional as an enzyme in fission yeast, and that it behaves in a similar manner as it does in HIV-1 infection. HIV-1 PR-induced cell death in fission yeast could potentially be used as an endpoint for mechanistic studies, and this system could be used for developing a high-throughput system for drug screenings.

Normal Cellular Prion Protein Protects against Manganese-induced Oxidative Stress and Apoptotic Cell Death

PubMed Central

Choi, Christopher J.; Anantharam, Vellareddy; Saetveit, Nathan J.; Houk, Robert. S.; Kanthasamy, Arthi; Kanthasamy, Anumantha G.

2012-01-01

The normal prion protein is abundantly expressed in the CNS, but its biological function remains unclear. The prion protein has octapeptide repeat regions that bind to several divalent metals, suggesting that the prion proteins may alter the toxic effect of environmental neurotoxic metals. In the present study, we systematically examined whether prion protein modifies the neurotoxicity of manganese (Mn) by comparing the effect of Mn on mouse neural cells expressing prion protein (PrPC -cells) and prion-knockout (PrPKO -cells). Exposure to Mn (10 μM-1 mM) for 24 hr produced a dose-dependent cytotoxic response in both PrPC -cells and PrPKO -cells. Interestingly, PrPC -cells (EC50 117.6μM) were more resistant to Mn-induced cytotoxicity, as compared to PrPKO -cells (EC50 59.9μM), suggesting a protective role for PrPC against Mn neurotoxicity. Analysis of intracellular Mn levels showed less Mn accumulation in PrPC -cells as compared to PrPKO -cells. Furthermore, Mn-induced mitochondrial depolarization and ROS generation were significantly attenuated in PrPC -cells as compared to PrPKO -cells. Measurement of antioxidant status revealed similar basal levels of glutathione (GSH) in PrPC -cells and PrPKO -cells; however, Mn treatment caused greater depletion of GSH in PrPKO -cells. Mn-induced mitochondrial depolarization and ROS production were followed by time- and dose-dependent activation of the apoptotic cell death cascade involving caspase-9 and -3. Notably, DNA fragmentation induced by both Mn treatment and oxidative stress-inducer hydrogen peroxide (100μM) was significantly suppressed in PrPC -cells as compared to PrPKO -cells. Together, these results demonstrate that prion protein interferes with divalent metal Mn uptake and protects against Mn-induced oxidative stress and apoptotic cell death. PMID:17483122

PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer

PubMed Central

Davenport, Kristen A.; Hoover, Clare E.; Bian, Jifeng; Telling, Glenn C.; Mathiason, Candace K.; Hoover, Edward A.

2017-01-01

The agent responsible for prion diseases is a misfolded form of a normal protein (PrPC). The prion hypothesis stipulates that PrPC must be present for the disease to manifest. Cervid populations across the world are infected with chronic wasting disease, a horizontally-transmissible prion disease that is likely spread via oral exposure to infectious prions (PrPCWD). Though PrPCWD has been identified in many tissues, there has been little effort to characterize the overall PrPC expression in cervids and its relationship to PrPCWD accumulation. We used immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay to describe PrPC expression in naïve white-tailed deer. We used real-time, quaking-induced conversion (RT-QuIC) to detect prion seeding activity in CWD-infected deer. We assessed tissues comprising the alimentary tract, alimentary-associated lymphoid tissue and systemic lymphoid tissue from 5 naïve deer. PrPC was expressed in all tissues, though expression was often very low compared to the level in the CNS. IHC identified specific cell types wherein PrPC expression is very high. To compare the distribution of PrPC to PrPCWD, we examined 5 deer with advanced CWD infection. Using RT-QuIC, we detected prion seeding activity in all 21 tissues. In 3 subclinical deer sacrificed 4 months post-inoculation, we detected PrPCWD consistently in alimentary-associated lymphoid tissue, irregularly in alimentary tract tissues, and not at all in the brain. Contrary to our hypothesis that PrPC levels dictate prion accumulation, PrPC expression was higher in the lower gastrointestinal tissues than in the alimentary-associated lymphoid system and was higher in salivary glands than in the oropharyngeal lymphoid tissue. These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs. PMID:28880938

"How I Wish This Thing Was Initiated 100 Years Ago!" Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya.

PubMed

Karuga, Robinson Njoroge; Njenga, Serah Nduta; Mulwa, Rueben; Kilonzo, Nduku; Bahati, Prince; O'reilley, Kevin; Gelmon, Lawrence; Mbaabu, Stephen; Wachihi, Charles; Githuka, George; Kiragu, Michael

2016-01-01

The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). 83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.

Ambiguity, ambivalence, and apprehensions of taking HIV-1 pre-exposure prophylaxis among male couples in San Francisco: a mixed methods study.

PubMed

Saberi, Parya; Gamarel, Kristi E; Neilands, Torsten B; Comfort, Megan; Sheon, Nicolas; Darbes, Lynae A; Johnson, Mallory O

2012-01-01

We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIV-positive) male couples' PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple. Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants' awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level of agreement with health care providers offering PrEP to anyone requesting it. We used multivariable regression to examine associations between PrEP questions and covariates of interest and employed an inductive approach to identify key qualitative themes. Among 328 men (164 couples), 62% had heard about PrEP, but approximately one-quarter were mistaking it with post-exposure prophylaxis. The majority of participants had low endorsement of PrEP uptake and 40% were uncertain if health care providers should offer PrEP to anyone requesting it. Qualitative interviews with 32 men suggest that this uncertainty likely stems from concerns regarding increased risk compensation. Likelihood of future PrEP uptake by the HIV-negative member of the couple was positively associated with unprotected insertive anal intercourse but negatively correlated with unprotected receptive anal intercourse. Findings suggest that those at greatest risk may not be receptive of PrEP. Those who engage in moderate risk express more interest in PrEP; however, many voice concerns of increased risk behavior in tandem with PrEP use. Results indicate a need for further education of MSM communities and the need to determine appropriate populations in which PrEP can have the highest impact.

Increased infectivity of anchorless mouse scrapie prions in transgenic mice overexpressing human prion protein.

PubMed

Race, Brent; Phillips, Katie; Meade-White, Kimberly; Striebel, James; Chesebro, Bruce

2015-06-01

Prion protein (PrP) is found in all mammals, mostly as a glycoprotein anchored to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) linkage. Following prion infection, host protease-sensitive prion protein (PrPsen or PrPC) is converted into an abnormal, disease-associated, protease-resistant form (PrPres). Biochemical characteristics, such as the PrP amino acid sequence, and posttranslational modifications, such as glycosylation and GPI anchoring, can affect the transmissibility of prions as well as the biochemical properties of the PrPres generated. Previous in vivo studies on the effects of GPI anchoring on prion infectivity have not examined cross-species transmission. In this study, we tested the effect of lack of GPI anchoring on a species barrier model using mice expressing human PrP. In this model, anchorless 22L prions derived from tg44 mice were more infectious than 22L prions derived from C57BL/10 mice when tested in tg66 transgenic mice, which expressed wild-type anchored human PrP at 8- to 16-fold above normal. Thus, the lack of the GPI anchor on the PrPres from tg44 mice appeared to reduce the effect of the mouse-human PrP species barrier. In contrast, neither source of prions induced disease in tgRM transgenic mice, which expressed human PrP at 2- to 4-fold above normal. Prion protein (PrP) is found in all mammals, usually attached to cells by an anchor molecule called GPI. Following prion infection, PrP is converted into a disease-associated form (PrPres). While most prion diseases are species specific, this finding is not consistent, and species barriers differ in strength. The amino acid sequence of PrP varies among species, and this variability affects prion species barriers. However, other PrP modifications, including glycosylation and GPI anchoring, may also influence cross-species infectivity. We studied the effect of PrP GPI anchoring using a mouse-to-human species barrier model. Experiments showed that prions produced by mice expressing only anchorless PrP were more infectious than prions produced in mice expressing anchored PrP. Thus, the lack of the GPI anchor on prions reduced the effect of the mouse-human species barrier. Our results suggest that prion diseases that produce higher levels of anchorless PrP may pose an increased risk for cross-species infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Molecular cloning and characterization of two novel genes from hexaploid wheat that encode double PR-1 domains coupled with a receptor-like protein kinase

USDA-ARS?s Scientific Manuscript database

Hexaploid wheat (Triticum aestivum L.) contains at least 23 TaPr-1 genes encoding the group 1 pathogenesis-related (PR-1) proteins as identified in our previous work. Here we report the cloning and characterization of TaPr-1-rk1 and TaPr-1-rk2, two novel genes closely related to the wheat PR-1 famil...

Global Precipitation Measurement (GPM) Validation Network

NASA Technical Reports Server (NTRS)

Schwaller, Mathew; Moris, K. Robert

2010-01-01

The method averages the minimum TRMM PR and Ground Radar (GR) sample volumes needed to match-up spatially/temporally coincident PR and GR data types. PR and GR averages are calculated at the geometric intersection of the PR rays with the individual Ground Radar(GR)sweeps. Along-ray PR data are averaged only in the vertical, GR data are averaged only in the horizontal. Small difference in PR & GR reflectivity high in the atmosphere, relatively larger differences. Version 6 TRMM PR underestimates rainfall in the case of convective rain in the lower part of the atmosphere by 30 to 40 percent.

Knowledge of and interest in using preexposure prophylaxis for HIV prevention among men who have sex with men in Thailand.

PubMed

Sineath, R Craig; Finneran, Catherine; Sullivan, Patrick; Sanchez, Travis; Smith, Dawn K; Griensven, Frits van; Wimonsate, Wipas; Stephenson, Rob

2013-01-01

Little is known about HIV preexposure prophylaxis (PrEP) acceptability among men who have sex with men (MSM) in Thailand. The authors recruited an online convenience sample of Thai MSM (n = 404) to assess the knowledge of and interest in PrEP. Less than 7% had heard of PrEP; however, 35% indicated interest in PrEP after an explanation of its possible efficacy. Regression modeling demonstrated that HIV knowledge and risk behavior, but not demographics, are significant predictors of PrEP interest. More information and education about PrEP is necessary and more research is needed to examine PrEP acceptability and to inform the message for PrEP uptake.

Immunoreactivity of specific epitopes of PrPSc is enhanced by pretreatment in a hydrated autoclave.

PubMed Central

Yokoyama, T; Momotani, E; Kimura, K; Yuasa, N

1996-01-01

An abnormal protein (PrPSc) accumulates in animals affected with scrapie. Immunoblotting procedures have been used widely to detect PrPSc. Blotted membranes were subjected to pretreatment in a hydrated autoclave, and the subsequent immunoreactivity of PrPSc was examined. The immunoreactivity of PrPSc to antisera against the synthetic peptides of the mouse PrP amino acid sequences 199 to 208 and 213 to 226 was enhanced by the pretreatment. However, the reactivity to antisera of peptide sequences 100 to 115 and 165 to 174 was not affected. The antibody-binding ability of the specific epitopes which are located close to the C-terminal end of PrP27-30 the proteinase-resistant portion of PrPSc, was enhanced by pretreatment in a hydrated autoclave. This pretreatment increased the sensitivity of PrPSc, and it would be useful for diagnosis of scrapie. PMID:8807215

Synthesis and Biological Evaluation of Water-soluble Progesterone-Conjugated Probes for Magnetic Resonance Imaging of Hormone Related Cancers

PubMed Central

Sukerkar, Preeti A.; MacRenaris, Keith W.; Townsend, Taryn R.; Ahmed, Roshan A.; Burdette, Joanna E.; Meade, Thomas J.

2011-01-01

Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(−) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(−) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases. PMID:21972997

Structural and electrochemical characterization of carbon supported Pt-Pr catalysts for direct ethanol fuel cells prepared using a modified formic acid method in a CO atmosphere.

PubMed

Corradini, Patricia Gon; Antolini, Ermete; Perez, Joelma

2013-07-28

Pt-Pr/C electrocatalysts were prepared using a modified formic acid method, and their activity for carbon monoxide and ethanol oxidation was compared to Pt/C. No appreciable alloy formation was detected by XRD analysis. By TEM measurements it was found that Pt particle size increases with an increasing Pr content in the catalysts and with decreasing metal precursor addition time. XPS measurements indicated Pt segregation on the catalyst surface and the presence of Pr2O3 and PrO2 oxides. The addition of Pr increased the electro-catalytic activity of Pt for both CO and CH3CH2OH oxidation. The enhanced activity of Pt-Pr/C catalysts was ascribed to both an electronic effect, caused by the presence of Pr2O3, and the bi-functional mechanism, caused by the presence of PrO2.

In-silico analysis of cis-acting regulatory elements of pathogenesis-related proteins of Arabidopsis thaliana and Oryza sativa

PubMed Central

Kaur, Amritpreet; Pati, Pratap Kumar; Pati, Aparna Maitra; Nagpal, Avinash Kaur

2017-01-01

Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation. CpG islands are observed only in rice PRs, which indicates that monocot genome contains more GC rich motifs than dicots. Tandem repeats were also observed in 5’ UTR of PR genes. Thus, the present study provides an understanding of regulation of PR genes and their versatile roles in plants. PMID:28910327

How Stigma Surrounding the Use of HIV Preexposure Prophylaxis Undermines Prevention and Pleasure: A Call to Destigmatize "Truvada Whores".

PubMed

Calabrese, Sarah K; Underhill, Kristen

2015-10-01

Antiretroviral preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate [Truvada]) prevents HIV without penalizing sexual pleasure, and may even enhance pleasure (e.g., by reducing HIV-related anxiety). However, concern about sexual risk behavior increasing with PrEP use (risk compensation) and corresponding stereotypes of promiscuity may undermine PrEP's preventive potential. In this commentary, we review literature on sexual behavior change accompanying PrEP use, discuss risk compensation concerns and the "Truvada whore" stereotype as PrEP barriers, question the appropriateness of restricting PrEP access because of risk compensation, and consider sexual pleasure as a benefit of PrEP, an acceptable motive for seeking PrEP, and a core element of health. It is essential for science to trump stereotypes and sex-negative messaging in guiding decision-making affecting PrEP access and uptake.

In-silico analysis of cis-acting regulatory elements of pathogenesis-related proteins of Arabidopsis thaliana and Oryza sativa.

PubMed

Kaur, Amritpreet; Pati, Pratap Kumar; Pati, Aparna Maitra; Nagpal, Avinash Kaur

2017-01-01

Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation. CpG islands are observed only in rice PRs, which indicates that monocot genome contains more GC rich motifs than dicots. Tandem repeats were also observed in 5' UTR of PR genes. Thus, the present study provides an understanding of regulation of PR genes and their versatile roles in plants.

Threefold Increase in PrEP Uptake Over Time with High Adherence Among Young Men Who Have Sex With Men in Chicago.

PubMed

Morgan, Ethan; Moran, Kevin; Ryan, Daniel T; Mustanski, Brian; Newcomb, Michael E

2018-05-04

The goal of this work is to better understand utilization and uptake of pre-exposure prophylaxis (PrEP) among young men who have sex with men (YMSM) and transgender women (TGW). We assessed trends and correlates of PrEP use and adherence across three time points of longitudinal data collection among 885 YMSM and TGW (aged 16-29) from the RADAR cohort in Chicago, 2015-2017. Past 6-month PrEP use increased across three visits: from 6.6 to 17.5%. In multivariable models, past 6-month PrEP use was significantly associated with participation in condomless sex, having more sexual partners, and older age. At least three-quarters of current PrEP users reported being ≥ 90% adherent to PrEP medication across all visits. Past 6-month PrEP use increased over time with those who participated in high-risk HIV behaviors also those most likely to have taken PrEP. As PrEP uptake continues to rise, more research will be needed to understand predictors of PrEP usage, as well as patterns of sexual behavior change following uptake.

Small Molecule Regulation of Protein Conformation by Binding in the Flap of HIV Protease

PubMed Central

Tiefenbrunn, Theresa; Forli, Stefano; Baksh, Michael M.; Chang, Max W.; Happer, Meaghan; Lin, Ying-Chuan; Perryman, Alexander L.; Rhee, Jin-Kyu; Torbett, Bruce E.; Olson, Arthur J.; Elder, John H.; Finn, M. G.; Stout, C. David

2013-01-01

The fragment indole-6-carboxylic acid (1F1), previously identified as a flap site binder in a fragment-based screen against HIV protease (PR), has been co-crystallized with pepstatin-inhibited PR and with apo-PR. Another fragment, 3-indolepropionic acid (1F1-N), predicted by AutoDock calculations and confirmed in a novel ‘inhibition of nucleation’ crystallization assay, exploits the same interactions in the flap site in two crystal structures. Both 1F1 and 1F1-N bind to the closed form of apo-PR and to pepstatin:PR. In solution, 1F1 and 1F1-N raise the Tm of apo-PR by 3.5–5 °C as assayed by differential scanning fluorimetry (DSF), and show equivalent low-micromolar binding constants to both apo-PR and pepstatin:PR, assayed by backscattering interferometry (BSI). The observed signal intensities in BSI are greater for each fragment upon binding to apo-PR than to pepstatin-bound PR, consistent with greater conformational change in the former binding event. Together, these data indicate that fragment binding in the flap site favors a closed conformation of HIV PR. PMID:23540839

Crystal growth and scintillation properties of Pr-doped SrI2 single crystals

NASA Astrophysics Data System (ADS)

Yokota, Yuui; Ito, Tomoki; Yoshino, Masao; Yamaji, Akihiro; Ohashi, Yuji; Kurosawa, Shunsuke; Kamada, Kei; Yoshikawa, Akira

2018-04-01

Pr-doped SrI2 (Pr:SrI2) single crystals with various Pr concentrations were grown by the halide-micro-pulling-down (H-μ-PD) method, and the scintillation properties were investigated. Pr1%:SrI2 single crystal with high transparency could be grown by the H-μ-PD method while Pr2, 3 and 5%:SrI2 single crystals included some cracks and opaque parts. In the photoluminescence spectrum of the Pr1%:SrI2 single crystal, an emission peak originated from the Pr3+ ion was observed around 435 nm while the radioluminescence spectra showed an emission peak around 535 nm for the undoped SrI2 and Pr:SrI2 single crystals. Light yields of Pr1, 2, 3 and 5%:SrI2 single crystals under γ-ray irradiation were 7700, 8700, 7200 and 6700 photons/MeV, respectively. Decay times of Pr1 and 2%:SrI2 single crystals under γ-ray irradiation were 55.9 and 35.0 ns of the fast decay component, and 435 and 408 ns of the slow decay component, respectively.

Willingness to Self-Pay for Pre-exposure Prophylaxis in Men Who Have Sex With Men: A National Online Survey in Taiwan.

PubMed

Ko, Nai-Ying; Chen, Bo-Jie; Li, Chia-Wen; Ku, Wen-Wei; Hsu, Su-Ting

2016-04-01

High cost of pre-exposure prophylaxis (PrEP) is a major concern for acceptability. This study determined the willingness of men who have sex with men to self-pay for PrEP and factors associated with the likelihood of condom use if taking PrEP. The Taiwan 2014 MSM Online Sex Survey was conducted and data such as demographics, attitudes toward PrEP, and sexual behaviors in the previous 3 months were collected. Of the 1,151 MSM who participated, 56% were willing to take PrEP, but only 23% were willing to self-pay $340 for PrEP. Willingness to self-pay for PrEP was significantly associated with the previous receipt of nonoccupational post-exposure prophylaxis (adjusted odds ratio [AOR], 3.02, 95%CI [1.49, 6.12]), and positive attitudes toward PrEP (AOR, 3.02, 95%CI [2.19, 4.17]). Of MSM who are willing to use PrEP, 73.6% would maintain condom use if taking PrEP. If PrEP is made available in Taiwan, more efforts should be focused on increasing awareness of MSM who are practicing risky behaviors.

Energy transfer and radiative recombination processes in (Gd, Lu)3Ga3Al2O12:Pr3+ scintillators

NASA Astrophysics Data System (ADS)

Wu, Yuntao; Ren, Guohao

2013-10-01

(GdxLu3-x)Ga3Al2O12:0.3 at.%Pr (x = 0.025, 0.05, 0.1, 0.2, 0.4, 0.6) (GLGAG:Pr) polycrystalline powders are prepared by solid-state reaction method. To better understand the luminescence mechanism, the optical diffuse reflectance, photoluminescence emission and excitation, X-ray excited luminescence spectra and decay kinetics of GLGAG:Pr were investigated in detailed, allowing the determination of energy transfer from 5d state of Pr3+ to 4f state of Gd3+, and the non-radiative relaxation from 5d to 4f state of Pr3+. Besides, the former process plays more negative role in the emission quenching of GLGAG:Pr than later one. Pr3+ ion is regarded as an ineffective activation ion in Gd-based multicomponent aluminate garnets. In addition, the wavelength-resolved thermoluminescence spectra of GLGAG:Pr were studied after UV and X-ray irradiation. It is revealed that the localized recombination processes from electron traps to lower lying 4f levels of Pr3+ occurs without populating the higher 5d levels of Pr3+.

Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.

PubMed

Mosley, Jonathan D; Shoemaker, M Benjamin; Wells, Quinn S; Darbar, Dawood; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Witte, John S; Denny, Josh C; Roden, Dan M

2017-04-01

One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability. We used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=-0.88; P =0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47; P =0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83-0.95; P =0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=-0.03 [0.16]). The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity. © 2017 American Heart Association, Inc.

Enhanced stabilization of Pb, Zn, and Cd in contaminated soils using oxalic acid-activated phosphate rocks.

PubMed

Zhang, Zhuo; Guo, Guanlin; Wang, Mei; Zhang, Jia; Wang, Zhixin; Li, Fasheng; Chen, Honghan

2018-01-01

Phosphate amendments, especially phosphate rock (PR), are one of the most commonly used materials to stabilize heavy metals in contaminated soils. However, most of PR reserve consists of low-grade ore, which limits the efficiency of PR for stabilizing heavy metals. This study was to enhance the stabilization of heavy metals through improving the available phosphorous (P) release of PR by oxalic acid activation. Raw PR and activated PR (APR) were characterized by scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), X-ray powder diffraction (XRD), Brunauer-Emmett-Teller (BET) surface analysis, and laser diffraction to determine the changes of structure and composition of APR. The stabilization effectiveness of lead (Pb), zinc (Zn), and cadmium (Cd) in soils by APR was investigated through toxicity leaching test and speciation analysis. The results indicated that after treatment by oxalic acid, (1) the crystallinity of the fluorapatite phase of PR transformed into the weddellite phase; (2) the surface area of PR increased by 37%; (3) the particle size of PR became homogenized (20-70 μm); and (4) the available P content in PR increased by 22 times. These changes of physicochemical characteristics of PR induced that APR was more effective to transform soil heavy metals from the non-residual fraction to the residual fraction and enhance the stabilization efficiency of Pb, Zn, and Cd than PR. These results are significant for the future use of low-grade PR to stabilize heavy metals.

PrP(C) signalling in neurons: from basics to clinical challenges.

PubMed

Hirsch, Théo Z; Hernandez-Rapp, Julia; Martin-Lannerée, Séverine; Launay, Jean-Marie; Mouillet-Richard, Sophie

2014-09-01

The cellular prion protein PrP(C) was identified over twenty-five years ago as the normal counterpart of the scrapie prion protein PrP(Sc), itself the main if not the sole component of the infectious agent at the root of Transmissible Spongiform Encephalopathies (TSEs). PrP(C) is a ubiquitous cell surface protein, abundantly expressed in neurons, which constitute the targets of PrP(Sc)-mediated toxicity. Converging evidence have highlighted that neuronal, GPI-anchored PrP(C) is absolutely required for prion-induced neuropathogenesis, which warrants investigating into the normal function exerted by PrP(C) in a neuronal context. It is now well-established that PrP(C) can serve as a cell signalling molecule, able to mobilize transduction cascades in response to interactions with partners. This function endows PrP(C) with the capacity to participate in multiple neuronal processes, ranging from survival to synaptic plasticity. A diverse array of data have allowed to shed light on how this function is corrupted by PrP(Sc). Recently, amyloid Aβ oligomers, whose accumulation is associated with Alzheimer's disease (AD), were shown to similarly instigate toxic events by deviating PrP(C)-mediated signalling. Here, we provide an overview of the various signal transduction cascades ascribed to PrP(C) in neurons, summarize how their subversion by PrP(Sc) or Aβ oligomers contributes to TSE or AD neuropathogenesis and discuss the ensuing clinical implications. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

HIV-negative male couples' attitudes about pre-exposure prophylaxis (PrEP) and using PrEP with a sexual agreement.

PubMed

Mitchell, Jason W; Lee, Ji-Young; Woodyatt, Cory; Bauermeister, José; Sullivan, Patrick; Stephenson, Rob

2016-08-01

One efficacious strategy to help prevent HIV is oral pre-exposure prophylaxis (PrEP), a daily regimen of antiretroviral treatment taken by HIV-negative individuals. Two of the recommendations of Centers for Disease Control and Prevention (CDC) guidelines for PrEP pertain to being in a relationship (i.e., male couples). Despite the recognition of how primary partners in male couples' relationships shape HIV risk and CDC's PrEP guidelines, there is a paucity of data that examine HIV-negative male couples' attitudes toward PrEP use and using PrEP with a sexual agreement. A sexual agreement is an explicit agreement made between two individuals about what sex and other related behaviors may occur within and outside of their relationship. In this qualitative study, we examine HIV-negative male couples' attitudes toward PrEP use and whether they thought PrEP could be integrated into a sexual agreement. Data for this study are drawn from couple-level interviews conducted in 2014 with 29 HIV-negative male couples who had a sexual agreement and were from Atlanta or Detroit. Both passive (e.g., flyers) and active (e.g., targeted Facebook advertisements) recruitment methods were used; the sample was stratified by agreement type. Thematic analysis was applied to identify the following themes regarding HIV-negative male couples' attitudes toward PrEP use: (1) PrEP and condom use; (2) concerns about PrEP (e.g., effectiveness, side effects, and promoting sexually risky behavior); and (3) accessibility of PrEP. Some thought PrEP could be a part of couples' agreement because it could help reduce sexual anxiety and sexual risk, and would help keep the couple safe. Others described PrEP use with an agreement as something for "others". Some were also concerned that incorporating PrEP could usurp the need for a sexual agreement in a couples' relationship. These themes highlight the need to improve informational messaging and promotion efforts about PrEP among HIV-negative male couples who may benefit from using it.

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility*

PubMed Central

Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

2016-01-01

The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. “Knocking out” PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. PMID:26683373

A novel capture-ELISA for detection of anti-neutrophil cytoplasmic antibodies (ANCA) based on c-myc peptide recognition in carboxy-terminally tagged recombinant neutrophil serine proteases.

PubMed

Lee, Augustine S; Finkielman, Javier D; Peikert, Tobias; Hummel, Amber M; Viss, Margaret A; Specks, Ulrich

2005-12-20

Testing for antineutrophil cytoplasmic antibodies (ANCA) reacting with proteinase 3 (PR3) is part of the routine diagnostic evaluation of patients with small vessel vasculitis. For PR3-ANCA detection, capture ELISAs are reported to be superior to direct ELISAs. Standard capture ELISAs, in which PR3 is anchored by anti-PR3 monoclonal antibodies (moAB), have two potential disadvantages. First, the capturing moAB may compete for epitopes recognized by some PR3-ANCA, causing occasional false-negative results. Second, the capture of recombinant PR3 mutant molecules becomes unpredictable as modifications of specific conformational epitopes may not only affect the binding of PR3-ANCA, but also the affinity of the capturing anti-PR3 moAB. Here, we describe a new capture ELISA, and its application for PR3-ANCA detection. This new assay is based on the standardized capture of a variety of different carboxy-terminally c-myc tagged recombinant ANCA target antigens using anti-c-myc coated ELISA plates. Antigen used include c-myc tagged human rPR3 variants (mature and pro-form conformations), mouse mature rPR3 and human recombinant neutrophil elastase. This new anti-c-myc-capture ELISA for PR3-ANCA detection has an intra- and inter-assay coefficient of variation of 3.6% to 7.7%, and 15.8% to 18.4%, respectively. The analytical sensitivity and specificity for PR3-ANCA positive serum samples were 93% and 100%, respectively when rPR3 with mature conformation was used as target antigen, and 83% and 100% when the pro-enzyme conformation was employed. In conclusion, this new anti-c-myc capture ELISA compares favorably to our standard capture ELISA for PR3-ANCA detection, enables the unified capture of different ANCA target antigens through binding to a c-myc tag, and allows capture of rPR3 mutants necessary for PR3-ANCA epitope mapping studies.

Electron mobility limited by optical phonons in wurtzite InGaN/GaN core-shell nanowires

NASA Astrophysics Data System (ADS)

Liu, W. H.; Qu, Y.; Ban, S. L.

2017-09-01

Based on the force-balance and energy-balance equations, the optical phonon-limited electron mobility in InxGa1-xN/GaN core-shell nanowires (CSNWs) is discussed. It is found that the electrons tend to distribute in the core of the CSNWs due to the strong quantum confinement. Thus, the scattering from first kind of the quasi-confined optical (CO) phonons is more important than that from the interface (IF) and propagating (PR) optical phonons. Ternary mixed crystal and size effects on the electron mobility are also investigated. The results show that the PR phonons exist while the IF phonons disappear when the indium composition x < 0.047, and vice versa. Accordingly, the total electron mobility μ first increases and then decreases with indium composition x, and reaches a peak value of approximately 3700 cm2/(V.s) when x = 0.047. The results also show that the mobility μ increases as increasing the core radius of CSNWs due to the weakened interaction between the electrons and CO phonons. The total electron mobility limited by the optical phonons exhibits an obvious enhancement as decreasing temperature or increasing line electron density. Our theoretical results are expected to be helpful to develop electronic devices based on CSNWs.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues.

PubMed

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M; Zhou, Xinchun

2014-10-01

Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data in benign and malignant tissues from the same organ/tissue were then compared using the Student's t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (in either the nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC scores for any S1PR (cytoplasmic or nuclear) between benign and malignant changes. This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Systemic distribution, subcellular localization and differential expression of sphingosine-1-phosphate receptors in benign and malignant human tissues

PubMed Central

Wang, Chunyi; Mao, Jinghe; Redfield, Samantha; Mo, Yinyuan; Lage, Janice M.; Zhou, Xinchun

2014-01-01

Aims Five sphingosine-1-phosphate receptors (S1PR): S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5 (S1PR1-5) have been shown to be involved in the proliferation and progression of various cancers. However, none of the S1PRs have been systemically investigated. In this study, we performed immunohistochemistry (IHC) for S1PR1-S1PR5 on different tissues, in order to simultaneously determine the systemic distribution, subcellular localization and expression level of all five S1PRs. Methods We constructed tissue microarrays (TMAs) from 384 formalin-fixed paraffin-embedded (FFPE) blocks containing 183 benign and 201 malignant tissues from 34 human organs/systems. Then we performed IHC for all five S1PRs simultaneously on these TMA slides. The distribution, subcellular localization and expression of each S1PR were determined for each tissue. The data were then compared in benign and malignant tissues from the same organ/tissue using the student t-test. In order to reconfirm the subcellular localization of each S1PR as determined by IHC, immunocytochemistry (ICC) was performed on several malignant cell lines. Results We found that all five S1PRs are widely distributed in multiple human organs/systems. All S1PRs are expressed in both the cytoplasm and nucleus, except S1PR3, whose IHC signals are only seen in the nucleus. Interestingly, the S1PRs are rarely expressed on cellular membranes. Each S1PR is unique in its organ distribution, subcellular localization and expression level in benign and malignant tissues. Among the five S1PRs, S1PR5 has the highest expression level (either in nucleus or cytoplasm), with S1PR1, 3, 2 and 4 following in descending order. Strong nuclear expression was seen for S1PR1, S1PR3 and S1PR5, whereas S1PR2 and S1PR4 show only weak staining. Four organs/tissues (adrenal gland, liver, brain and colon) show significant differences in IHC scores for the multiple S1PRs (nuclear and/or cytoplasmic), nine (stomach, lymphoid tissues, lung, ovary, cervix, pancreas, skin, soft tissues and uterus) show differences for only one S1PR (cytoplasmic or nuclear), and twenty three organs/tissues show no significant difference in IHC score of any S1PR (cytoplasmic or nuclear) between benign and malignant changes. Conclusion This is the first study to evaluate the expression level of all S1PRs in benign and malignant tissues from multiple human organs. This study provides data regarding the systemic distribution, subcellular localization and differences in expression of all five S1PRs in benign and malignant changes for each organ/tissue. PMID:25084322

Investigation of carrier escape and recombination dynamics in GaAsN/GaAs superlattice and resonantly coupled quantum well solar cells

NASA Astrophysics Data System (ADS)

Kharel, Khim; Freundlich, Alexandre

2018-02-01

III-V multijunction devices that incorporate a dilute nitride 1-1.2 eV bottom cell have already demonstrated conversion efficiencies of about 44% under high sunlight concentration (942 Suns). However, the poor minority carrier properties of dilute nitride have, thus far, prevented the full realization of the practical potential for tandem configuration (>40% 1 sun, and >50% at 500X and above). To overcome this shortcoming, our group, over the past years, have focused on dilute nitride-based devices where the degraded minority carrier diffusion length has a minimal impact on the device performance. We have shown that the incorporation of resonantly coupled GaAsN/GaP multi-quantum wells in the intrinsic region of p-i-n GaAs cells allows both a significant sub-GaAs-bandgap photon harvesting while maintaining a high open circuit voltage. Here, in order to gain a better understanding of photo-generated carrier escape and recombination mechanisms in these devices and further optimize the performance, we examine optical and electrical properties of such devices using various characterization techniques such as: photoluminescence (PL), modulated photo-reflectance (PR), photo-current (PC) as well as current-voltage (IV) measurements under dark or illuminated conditions. The temperature dependent analysis enables us to modulate and freezes carrier thermalization phenomena, while simultaneous measurement of photogenerated carrier extraction (SR) and recombination's (PL) as a function of the applied load (bias) enables a close correlation between the evolution of I-V characteristics and the physics at play. Next, typical temperature and bias dependent activation energies reveal interesting details about carrier escape, intra-cells coupling and recombination sequences.

A Cross-Sectional Online Survey of HIV Pre-Exposure Prophylaxis Adoption Among Primary Care Physicians.

PubMed

Blackstock, Oni J; Moore, Brent A; Berkenblit, Gail V; Calabrese, Sarah K; Cunningham, Chinazo O; Fiellin, David A; Patel, Viraj V; Phillips, Karran A; Tetrault, Jeanette M; Shah, Minesh; Edelman, E Jennifer

2017-01-01

Among health care providers, prescription of HIV pre-exposure prophylaxis (PrEP) has been low. Little is known specifically about primary care physicians (PCPs) with regard to PrEP awareness and adoption (i.e., prescription or referral), and factors associated with adoption. To assess PrEP awareness, PrEP adoption, and factors associated with adoption among PCPs. Cross-sectional online survey conducted in April and May 2015. Members of a national professional organization for academic primary care physicians (n = 266). PrEP awareness, PrEP adoption (ever prescribed or referred a patient for PrEP [yes/no]), provider and practice characteristics, and self-rated knowledge, attitudes, and beliefs associated with adoption. The survey response rate was 8.6 % (266/2093). Ninety-three percent of respondents reported prior awareness of PrEP. Of these, 34.9 % reported PrEP adoption. In multivariable analysis of provider and practice characteristics, compared with non-adopters, adopters were more likely to provide care to more than 50 HIV-positive patients (vs. 0, aOR = 6.82, 95 % CI 2.06-22.52). Compared with non-adopters, adopters were also more likely to report excellent, very good, or good self-rated PrEP knowledge (15.1 %, 33.7 %, 30.2 % vs. 2.5 %, 18.1 %, 23.8 %, respectively; p < 0.001) and to perceive PrEP as extremely safe (35.1 % vs. 10.7 %; p = 0.002). Compared with non-adopters, adopters were less likely to perceive PrEP as being moderately likely to increase risk behaviors ("risk compensation") (12.8 % vs. 28.8 %, p = 0.02). While most respondents were aware of PrEP, only one-third of PrEP-aware PCPs reported adoption. Adopters were more likely to have experience providing HIV care and to perceive PrEP as extremely safe, and were less likely to perceive PrEP use as leading to risk compensation. To enhance PCP adoption of PrEP, educational efforts targeting PCPs without HIV care experience should be considered, as well as training those with HIV care experience to be PrEP "clinical champions". Concerns about safety and risk compensation must also be addressed.

Enhanced stability of monomer fold correlates with extreme drug resistance of HIV-1 protease.

PubMed

Louis, John M; Tözsér, József; Roche, Julien; Matúz, Krisztina; Aniana, Annie; Sayer, Jane M

2013-10-29

During treatment, mutations in HIV-1 protease (PR) are selected rapidly that confer resistance by decreasing affinity to clinical protease inhibitors (PIs). As these unique drug resistance mutations can compromise the fitness of the virus to replicate, mutations that restore conformational stability and activity while retaining drug resistance are selected on further evolution. Here we identify several compensating mechanisms by which an extreme drug-resistant mutant bearing 20 mutations (PR20) with >5-fold increased Kd and >4000-fold decreased affinity to the PI darunavir functions. (1) PR20 cleaves, albeit poorly, Gag polyprotein substrates essential for viral maturation. (2) PR20 dimer, which exhibits distinctly enhanced thermal stability, has highly attenuated autoproteolysis, thus likely prolonging its lifetime in vivo. (3) The enhanced stability of PR20 results from stabilization of the monomer fold. Both monomeric PR20(T26A) and dimeric PR20 exhibit Tm values 6-7.5 °C higher than those for their PR counterparts. Two specific mutations in PR20, L33F and L63P at sites of autoproteolysis, increase the Tm of monomeric PR(T26A) by ~8 °C, similar to PR20(T26A). However, without other compensatory mutations as seen in PR20, L33F and L63P substitutions, together, neither restrict autoproteolysis nor significantly reduce binding affinity to darunavir. To determine whether dimer stability contributes to binding affinity for inhibitors, we examined single-chain dimers of PR and PR(D25N) in which the corresponding identical monomer units were covalently linked by GGSSG sequence. Linking of the subunits did not appreciably change the ΔTm on inhibitor binding; thus stabilization by tethering appears to have little direct effect on enhancing inhibitor affinity.

The importance of exercise self-efficacy for clinical outcomes in pulmonary rehabilitation.

PubMed

Selzler, Anne-Marie; Rodgers, Wendy M; Berry, Tanya R; Stickland, Michael K

2016-11-01

Pulmonary rehabilitation (PR) improves functional exercise capacity and health status in people with chronic obstructive pulmonary disease (COPD), although these outcomes are often not maintained following PR. Self-efficacy is a precursor to outcomes achievement, yet few studies have examined the importance of self-efficacy to outcome improvement during PR, or how it develops over time. Further, the contribution of exercise-specific self-efficacy to outcomes in PR is unknown. The aims of this study were to determine (a) whether baseline exercise self-efficacy predicts PR attendance and change in functional exercise capacity and health status over PR, and (b) if exercise self-efficacy changes with PR. Fifty-eight out of 64 patients with COPD completed PR and assessments of exercise self-efficacy (task, coping, scheduling), the 6-minute walk test (6MWT), and St. George's Respiratory Questionnaire (SGRQ) at the beginning and end of PR. Analyses were conducted to predict attendance, and change in 6MWT and SGRQ, while controlling for baseline demographic and clinical indicators. Change in 6MWT, SGRQ, and self-efficacy with PR was also examined. Clinically significant increases in the 6MWT and SGRQ were achieved with PR. Stronger task self-efficacy predicted better attendance, while stronger coping self-efficacy predicted greater 6MWT improvement. No variables predicted SGRQ change. Scheduling self-efficacy significantly improved with PR, whereas task and coping self-efficacy did not. Baseline exercise self-efficacy appears to be a determinant of rehabilitation attendance and functional exercise improvement with PR. Clinicians should evaluate and target exercise self-efficacy to maximize adherence and health outcome improvement with PR. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Interactions between inflammatory signals and the progesterone receptor in regulating gene expression in pregnant human uterine myocytes

PubMed Central

Lee, Yun; Sooranna, Suren R; Terzidou, Vasso; Christian, Mark; Brosens, Jan; Huhtinen, Kaisa; Poutanen, Matti; Barton, Geraint; Johnson, Mark R; Bennett, Phillip R

2012-01-01

The absence of a fall in circulating progesterone levels has led to the concept that human labour is associated with ‘functional progesterone withdrawal’ caused through changes in the expression or function of progesterone receptor (PR). At the time of labour, the human uterus is heavily infiltrated with inflammatory cells, which release cytokines to create a ‘myometrial inflammation’ via NF-κB activation. The negative interaction between NF-κB and PR, may represent a mechanism to account for ‘functional progesterone withdrawal’ at term. Conversely, PR may act to inhibit NF-κB function and so play a role in inhibition of myometrial inflammation during pregnancy. To model this inter-relationship, we have used small interfering (si) RNA-mediated knock-down of PR in human pregnant myocytes and whole genome microarray analysis to identify genes regulated through PR. We then activated myometrial inflammation using IL-1β stimulation to determine the role of PR in myometrial inflammation regulation. Through PR-knock-down, we found that PR regulates gene networks involved in myometrial quiescence and extracellular matrix integrity. Activation of myometrial inflammation was found to antagonize PR-induced gene expression, of genes normally upregulated via PR. We found that PR does not play a role in repression of pro-inflammatory gene networks induced by IL-1β and that only MMP10 was significantly regulated in opposite directions by IL-1β and PR. We conclude that progesterone acting through PR does not generally inhibit myometrial inflammation. Activation of myometrial inflammation does cause ‘functional progesterone withdrawal’ but only in the context of genes normally upregulated via PR. PMID:22435466

Primary care clinicians' experiences prescribing HIV pre-exposure prophylaxis at a specialized community health centre in Boston: lessons from early adopters.

PubMed

Krakower, Douglas S; Maloney, Kevin M; Grasso, Chris; Melbourne, Katherine; Mayer, Kenneth H

2016-01-01

An estimated 1.2 million Americans have indications for using antiretroviral pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at-risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists. During January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics. Thirty-two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11-33). Most clinicians reported testing and risk-reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians' practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future. In a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale-up of this efficacious intervention.

Stigma and Conspiracy Beliefs Related to Pre-exposure Prophylaxis (PrEP) and Interest in Using PrEP Among Black and White Men and Transgender Women Who Have Sex with Men

PubMed Central

Kalichman, Seth C.; Price, Devon; Finneran, Stephanie; Allen, Aerielle; Maksut, Jessica

2018-01-01

The HIV/AIDS epidemic in the US continues to persist, in particular, among race, sexual orientation, and gender minority populations. Pre-exposure prophylaxis (PrEP), or using antiretroviral medications for HIV prevention, is an effective option, but uptake of PrEP has been slow. Sociocultural barriers to using PrEP have been largely underemphasized, yet have the potential to stall uptake and, therefore, warrant further understanding. In order to assess the relationships between potential barriers to PrEP (i.e., PrEP stigma and conspiracy beliefs), and interest in PrEP, Black men and transgender women who have sex with men (BMTW, N = 85) and White MTW (WMTW, N = 179) were surveyed at a gay pride event in 2015 in a large southeastern US city. Bivariate and multivariate logistic regression analyses were completed to examine factors associated with PrEP interest. Among the full sample, moderate levels of PrEP awareness (63%) and low levels of use (9%) were observed. Believing that PrEP is for people who are promiscuous (stigma belief) was strongly associated with lack of interest in using PrEP, and individuals who endorsed this belief were more likely to report sexual risk taking behavior. Conspiracy beliefs related to PrEP were reported among a large minority of the sample (42%) and were more frequently reported among BMTW than WMTW. Given the strong emphasis on the use of biomedical strategies for HIV prevention, addressing sociocultural barriers to PrEP access is urgently needed and failure to do so will weaken the potential benefits of biomedical prevention. PMID:28108878

Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora

PubMed Central

Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

2016-01-01

This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora. PMID:27337148

Effect of progesterone receptor status on maspin synthesis via nitric oxide production in neutrophils in human breast cancer.

PubMed

Ganguly Bhattacharjee, Karabi; Bhattacharyya, Mau; Halder, Umesh Chandra; Jana, Pradipta; Sinha, Asru K

2014-09-01

Although progesterone receptor (PR) status, similarly to estrogen receptor status, is of prognostic importance in breast cancer, the involvement of the PR in breast cancer remains obscure. Studies were conducted to determine the function of the PR in neutrophils in the nitric oxide-induced synthesis of maspin, an anti-breast-cancer protein produced in nonmalignant mammary cells and in neutrophils in the circulation. PR status was determined by immunohistochemistry. Maspin synthesis was determined by in-vitro translation of messenger RNA and quantified by enzyme-linked immunosorbent assay. Nitric oxide was determined by the methemoglobin method. It was found that PR status in neutrophils was identical with that in malignant breast tissues. A Scatchard plot for progesterone binding to normal and PR-positive (PR+) neutrophils revealed that whereas normal neutrophils had 11.5 × 10(10) PR sites/cell with K d = 47.619 nM, PR+ neutrophils had 6.6 × 10(10) PR sites/cell with K d = 47.619 nM. The progesterone negative (PR-) neutrophils failed to bind to progesterone. Incubation of normal and PR+ neutrophils with 25 nM progesterone produced 1.317 μM NO and 2.329 nM maspin; the PR+ neutrophils produced 0.72 μM NO and 1.138 nM maspin. The PR- neutrophils failed to produce any NO or maspin in the presence of progesterone. Inhibition of progesterone-induced NO synthesis led to complete inhibition of maspin synthesis in all neutrophils. These results suggest that estrogen and progesterone complement each other in NO-induced maspin synthesis, and do not necessarily antagonize in the synthesis of the anti-breast-cancer protein.

Transient expression of progesterone receptor and cathepsin-l in human granulosa cells during the periovulatory period.

PubMed

García, Víctor; Kohen, Paulina; Maldonado, Carola; Sierralta, Walter; Muñoz, Alex; Villarroel, Claudio; Strauss, Jerome F; Devoto, Luigi

2012-03-01

To study in vivo the progesterone receptor (PR) expression levels in human granulosa cells (GCs) during the periovulatory period and the affect of the protein kinase A (PKA) pathway on PR expression and cathepsin-L expression-activation. Experimental study. University research unit. Twenty-five women of reproductive age. Follicular fluid and GCs obtained from spontaneous cycles before and during the normal luteinizing hormone surge, and samples obtained 36 hours after human chorionic gonadotropin (hCG) administration in patients undergoing in vitro fertilization. To determine PR, cathepsin-L messenger RNA (mRNA) analysis via real-time polymerase chain reaction, and protein of PR, cathepsin-L, and PKA in human GCs. The Western blot analysis revealed that bands of PR (isoform A) were the most abundant and that mRNA (PR-A and PR-B) have a temporal pattern of expression throughout the periovulatory period. The protein levels of PR and cathepsin-L were up-regulated by hCG. The abundance of PR was diminished in the presence of PKA inhibitor, and cathepsin-L with PR receptor antagonist. The transient expression of PR in human GCs of the preovulatory follicle suggests that PR and its ligand play a role in the activation of cathepsin-L, which is presumably involved in the degradation of the follicular extracellular matrix during human ovulation. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

Perceptions of and intentions to adopt HIV pre-exposure prophylaxis among black men who have sex with men in Los Angeles.

PubMed

Brooks, Ronald A; Landovitz, Raphael J; Regan, Rotrease; Lee, Sung-Jae; Allen, Vincent C

2015-12-01

This study assessed perceptions of pre-exposure prophylaxis (PrEP) and their association with PrEP adoption intention among a convenience sample of 224 low socioeconomic status black men who have sex with men (BMSM) residing in Los Angeles. Participants received educational information about PrEP and completed an in-person interview. More than half (60%) of the participants indicated a high intention to adopt PrEP. Younger BMSM (18-29 years) were twice as likely to report a high intention to adopt PrEP compared to older BMSM (30+ years). Only 33% of participants were aware of PrEP and no participant had ever used PrEP. Negative perceptions were associated with a lower PrEP adoption intention and included being uncomfortable taking an HIV medicine when HIV-negative and not knowing if there are long-term side effects of taking an HIV medication. These findings suggest that BMSM may adopt PrEP but that negative perceptions may limit its uptake among this population. In order to facilitate PrEP adoption among BMSM targeted educational and community awareness programmes are needed to provide accurate information on the benefits of PrEP and to address the negative perceptions of PrEP held by local BMSM populations. © The Author(s) 2015.

Overexpression of p62/SQSTM1 promotes the degradations of abnormally accumulated PrP mutants in cytoplasm and relieves the associated cytotoxicities via autophagy-lysosome-dependent way.

PubMed

Xu, Yin; Zhang, Jin; Tian, Chan; Ren, Ke; Yan, Yu-E; Wang, Ke; Wang, Hui; Chen, Cao; Wang, Jing; Shi, Qi; Dong, Xiao-Ping

2014-04-01

The protein of p62/sequestosome 1 (SQSTM1), a key cargo adaptor protein involved in autophagy-lysosome degradation, exhibits inclusion bodies structure in cytoplasm and plays a protective role in some models of neurodegenerative diseases. Some PrP mutants, such as PrP-CYTO and PrP-PG14, also form cytosolic inclusion bodies and trigger neuronal apoptosis either in cultured cells or in transgenic mice. Here, we demonstrated that the cellular p62/SQSTM1 incorporated into the inclusion bodies formed by expressing the abnormal PrP mutants, PrP-CYTO and PrP-PG14, in human embryonic kidney 293 cells. Overexpression of p62/SQSTM1 efficiently relieved the cytosolic aggregations and cell apoptosis induced by the abnormal PrPs. Autophagy-lysosome inhibitors instead of proteasome inhibitor sufficiently blocked the p62/SQSTM1-mediated degradations of abnormal PrPs. Overexpression of p62/SQSTM1 did not alter the levels of light chain 3 (LC3) in the cells expressing various PrPs. However, more complexes of p62/SQSTM1 with LC3 were detected in the cells expressing the misfolded PrPs. These data imply that p62/SQSTM1 plays an important role in the homeostasis of abnormal PrPs via autophagy-lysosome-dependent way.

What people want from sex and preexposure prophylaxis.

PubMed

Grant, Robert M; Koester, Kimberly A

2016-01-01

As demand for preexposure prophylaxis (PrEP) increases, we are learning more about what people want from sex and PrEP. PrEP demand has reached a tipping point in the USA and is increasing rapidly. Although the primary benefit of PrEP use is biological, to reduce risk of HIV infection, PrEP users often express an alternative set of social and emotional benefits that are provided by PrEP. These collateral benefits of PrEP have salience, affect, and are experienced in the present, which are compelling drivers of human behavior. PrEP use has been associated with feeling safe during sex, usually in contrast to ruminations related to fear of HIV or intimate partner violence or control. PrEP can create empowerment, or agency, defined as the capacity and autonomy to act on one's own behalf, because it provides control over one's vulnerability to HIV and relief to women and men who may otherwise worry about whether their partners will use a condom, take antiretroviral therapy, or disclose their HIV status accurately. Planning for sexual and social goals in calm moments is also empowering. These highly desired collateral benefits of PrEP could be undermined, or eliminated, if PrEP is implemented in ways that are coercive or that foment fear of sexual risk compensation, drug resistance, toxicity, or moral judgment. Current PrEP implementation provides direct and indirect benefits that are highly desired.

Preparing for pre-exposure prophylaxis: perceptions and readiness of Canadian pharmacists for the implementation of HIV pre-exposure prophylaxis.

PubMed

Yoong, Deborah; Naccarato, Mark; Sharma, Malika; Wilton, James; Senn, Heather; Tan, Darrell Hs

2016-07-01

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted. © The Author(s) 2015.

Analysis of the HIV-2 protease's adaptation to various ligands: characterization of backbone asymmetry using a structural alphabet.

PubMed

Triki, Dhoha; Cano Contreras, Mario Enrique; Flatters, Delphine; Visseaux, Benoit; Descamps, Diane; Camproux, Anne-Claude; Regad, Leslie

2018-01-15

The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly and binding various ligands. We propose an exhaustive study of the local structural asymmetry between the two monomers of all available PR2 structures complexed with various inhibitors using a structural alphabet approach. On average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting different backbone local conformations in the two monomers. This asymmetry was observed all along its structure, particularly in the elbow and flap regions. We first differentiated structural asymmetry conserved in most PR2 structures from the one specific to some PR2. Then, we explored the origin of the detected asymmetry in PR2. We localized asymmetry that could be induced by PR2's flexibility, allowing transition from the semi-open to closed conformations and the asymmetry potentially induced by ligand binding. This latter could be important for the PR2's adaptation to diverse ligands. Our results highlighted some differences between asymmetry of PR2 bound to darunavir and amprenavir that could explain their differences of affinity. This knowledge is critical for a better description of PR2's recognition and adaptation to various ligands and for a better understanding of the resistance of PR2 to most PR2 inhibitors, a major antiretroviral class.

Exploratory survey of Florida pharmacists' experience, knowledge, and perception of HIV pre-exposure prophylaxis.

PubMed

Shaeer, Kristy M; Sherman, Elizabeth M; Shafiq, Sami; Hardigan, Patrick

2014-01-01

To assess Florida pharmacists' experience, knowledge, and perception of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and to identify areas for pharmacist training. Cross-sectional survey. Florida in March through July 2013. Florida pharmacists. In-person and online anonymous survey. Florida pharmacists' experience, knowledge, and perceptions of PrEP. 225 completed surveys were analyzed. Survey respondents were predominantly community pharmacists with mean age of 45.7 years and less than 20 years of experience. Only 22% of respondents reported dispensing PrEP to patients. Although 75% had completed HIV-related continuing education in the last 2 years, 63% were unaware of Centers for Disease Control and Prevention PrEP guidelines and 71% answered that they did not have sufficient knowledge to counsel patients with PrEP prescriptions. Importantly, 47% of respondents answered they were uncomfortable counseling patients about PrEP. By self-report, most pharmacists agreed PrEP leads to risky behavior (68%) and increased rates of sexually transmitted infections (65%), and is too costly to promote patient access (92%). Surveyed Florida pharmacists reported limited understanding of PrEP. As a widely accessible health care counseling resource, pharmacists are positioned to improve patient understanding, promote medication adherence, and enhance PrEP efficacy. Especially during PrEP implementation, when patients may receive PrEP prescriptions from non-HIV specialist prescribers, improving pharmacists' PrEP education presents a salient opportunity.

Recent revisions of phosphate rock reserves and resources: a critique

NASA Astrophysics Data System (ADS)

Edixhoven, J. D.; Gupta, J.; Savenije, H. H. G.

2014-12-01

Phosphate rock (PR) is a finite mineral indispensable for fertilizer production, while P (phosphorus) is a major pollutant if applied or discharged in excess, causing widespread eutrophication (Carpenter and Bennet, 2011). High-grade PR is obtained from deposits which took millions of years to form and which are gradually being depleted. Recently, global PR reserves as reported by the US Geological Survey (USGS) have increased from 16 000 Mt PR in 2010 to 65 000 Mt PR in 2011 and further to 67 000 Mt PR in 2014. The majority of this 4-fold increase is based on a 2010 report by the International Fertilizer Development Center (IFDC), which increased Moroccan reserves from 5700 Mt PR as reported by USGS, to 51 000 Mt PR, reported as upgraded ("beneficiated") concentrate. The report also increased global resources from 163 000 Mt PR reported in the literature in 1989 to 290 000 Mt PR. IFDC used a simplified resource terminology which does not use the underlying thresholds for reserves and resources used in the USGS classification. IFDC proposed that agreement should be reached on PR resource terminology which should be as simple as possible. The report has profoundly influenced the PR scarcity debate, shifting the emphasis from resource scarcity to the pollution angle of the phosphate problem. In view of the high dependence of food production on PR and the importance of data on PR reserves and resources for scientific analysis and policy making, data on PR deposits should be transparent, comparable, reliable, and credible. We analyze (i) how IFDC's simplified terminology compares to international best practice in resource classification and whether it is likely to yield data that meet these requirements, (ii) whether the difference in volume between raw PR ore and upgraded PR concentrate is sufficiently noted in the literature, and (iii) whether the IFDC report presents an accurate picture of PR reserves and resources. We conclude that, while there is a global development toward common criteria in resource reporting, IFDC's lack of clear thresholds for reserves and resources contravenes this and that the vagueness of its definitions for reserves and resources may allow deposits to be termed reserves or resources which could not be recognized as such under leading mineral resource classifications. The difference between PR ore and PR concentrate is barely noted in the literature, causing pervasive confusion and a significant degree of error in many assessments. Finally, we find that the report most likely presents an inflated picture of global reserves, in particular those of Morocco, where the aggregate resources of three of the four Moroccan/Western Saharan major PR deposits appear to have been simply converted to "reserves". Following the release of the IFDC report, various analysts have concluded or suggested that the available PR deposits or even the currently reported resources would likely last several thousands of years at current consumption rates. However, the data on which these statements were based do not appear to warrant such a conclusion. Further research is required as to the quantity of PR deposits and their viability for future extraction, using uniform and transparent classification terminology.

Sex Differences in Pitch Range and Speech Fundamental Frequency After Arytenoid Adduction and Thyroplasty.

PubMed

Konomi, Ujimoto; Watanabe, Yusuke; Komazawa, Daigo

2016-05-01

The purpose of this study was to clarify the sex differences in pitch range (PR) and speech fundamental frequency (SFF) after arytenoid adduction (AA) combined with type 1 thyroplasty (TP1) in patients with unilateral vocal fold paralysis (UVFP) and to assess the cause of these differences. This is a retrospective review of clinical records. The records of 50 patients with UVFP for whom PR, SFF, and maximum phonation time (MPT) had been evaluated before and 1 year after AA combined with TP1 were analyzed. Patients consisted of 36 men and 14 women. In particular, in the 37 patients (24 men and 13 women) who had ≥2 semitones (STs) in preoperative PR (pre-PR), the differences and correlations between the pre-PR and the postoperative PR (post-PR), SFF, and MPT were compared between the sexes. We also discussed cases of post-PR deterioration and abnormal SFF. The characteristics of PR in men are narrow pre-PR (14.7 ± 11.5 STs) and significant extension of post-PR (22.6 ± 6.3 STs). MPT extended from 4.6 ± 2.5 seconds to 14.8 ± 7.2 seconds. In contrast, women had a wide pre-PR (18.1 ± 7.2 STs) and showed no significant post-PR extension (21.7 ± 7.8 STs). MPT extended from 5.1 ± 1.9 seconds to 16.8 ± 7.2 seconds. Although there were no significant changes in average SFF, as well as the highest and lowest pitch after the operation, the variance of the pre-SFF tended to converge into the physiological range in the post-SFF (P = 0.08). Compared with the SFF data of normal adult controls, post-SFF in the normal range was 46.0% (23/50). In patients who showed a >20% improvement in PR, normal post-SFF appeared in 68.8% of the patients (11/16). Particularly in those women, 83.3% (5/6) showed a normal post-SFF. Men showed greater difficulty in recovery of normal PR, SFF, and MPT; however, there were fewer patients (4.2%; 1/24) with a PR deterioration of >20%. Regarding women, although some patients showed a parallel recovery in PR and SFF to the normal range, there was a high rate of patients showing PR deterioration (30.8%; 4/13). AA combined with TP1 resulted in the recovery of not only MPT but also PR and SFF. In addition, sex differences in operative effects were suggested. In men, although MPT is difficult to be fully recovered, PR deterioration was mild. In women, although MPT was more easily extended, PR deterioration occurred more readily because of operative effects such as hypermedialization of their smaller larynx. The post-PR variation appeared to be associated with SFF. Our results indicate the necessity to assess patients' PR and SFF even if their MPTs recover, particularly in patients with postoperative voice insufficiency. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Quantifying the relative amounts of PrP polymorphisms present in prions isolated from heterozygous prion-infected animals

USDA-ARS?s Scientific Manuscript database

Prions cause protein misfolding diseases, such as transmissible spongiform encephalopathy. They propagate infections by converting a normal cellular prion protein into a prion (PrPSc). PrPC and PrPSc are isosequential and differ only in their respective conformations. PrPC is monomeric and sensit...

75 FR 57268 - Notice of Baseline Filings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-20

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-103-000; Docket No. PR10-104-000; Docket No. PR10-105- 000 (Not Consolidated)] Notice of Baseline Filings September 13, 2010. Duke Energy Ohio, Inc Docket No. PR10-103-000. Duke Energy Kentucky, Inc Docket No. PR10-104-000...

75 FR 65010 - Notice of Baseline Filings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-21

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR11-1-000; Docket No. PR11-2-000; Docket No. PR11-3-000] Notice of Baseline Filings October 14, 2010. Cranberry Pipeline Docket No. PR11-1-000 Corporation. New Mexico Gas Company, Inc.. Docket No. PR11-2-000 Peoples Natural Gas...

Prion protein conversion induced by trivalent iron in vesicular trafficking.

PubMed

Choi, Bo-Ran; Lee, Jeongmin; Kim, Su Yeon; Yim, Inbeen; Kim, Eun-Hee; Woo, Hee-Jong

2013-03-15

Iron dyshomeostasis has been observed in prion diseases; however, little is known regarding the contribution of the oxidation state of iron to prion protein (PrP) conversion. In this study, PrP(C)-deficient HpL3-4 cells were exposed to divalent [Fe(II)] or trivalent [Fe(III)] iron, followed by exogenous recombinant PrP (rPrP) treatment. We then analyzed the accumulation of internalized rPrP and its biochemical properties, including its resistance to both proteinase K (PK) digestion and detergent solubility. Fe(III), but not Fe(II), induced the accumulation of internalized rPrP, which was partially converted to detergent-insoluble and PK-resistant PrP (PrP(res)). The Fe(III)-induced PrP(res) generation required an intact cell structure, and it was hindered by U18666A, an inhibitor of vesicular trafficking, but not by NH4Cl, an inhibitor of endolysosomal acidification. These observations implicated that the Fe(III)-mediated PrP(res) conversion likely occurs during endosomal vesicular trafficking rather than in the acidic environment of lysosomes. Copyright © 2013 Elsevier Inc. All rights reserved.

PrEParing Women to Prevent HIV: An Integrated Theoretical Framework to PrEP Black Women in the United States.

PubMed

Chapman Lambert, Crystal; Marrazzo, Jeanne; Amico, K Rivet; Mugavero, Michael J; Elopre, Latesha

2018-04-05

Preexposure prophylaxis (PrEP) with optimal adherence has demonstrated efficacy in reducing HIV incidence in women. Black women are disproportionately burdened by the HIV epidemic, accounting for more than half of all new HIV cases in women, thereby making PrEP an ideal prevention strategy for this group. However, to date, PrEP uptake by women in the United States has been slow. Further domestic research is needed to understand the multilevel factors related to PrEP awareness, uptake, and implementation in Black women. Our purpose was to review the current status of HIV prevention in Black women. We summarize clinical trials germane to federal approval of PrEP; discuss important PrEP studies focused on women, including non-oral options; and review multilevel barriers to PrEP uptake. Lastly, we discuss the use of an integrated theoretical framework to organize multilevel factors related to PrEP uptake by Black women in order to guide intervention development. Copyright © 2018 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Framing HIV Pre-Exposure Prophylaxis (PrEP) for the General Public: How Inclusive Messaging May Prevent Prejudice from Diminishing Public Support.

PubMed

Calabrese, Sarah K; Underhill, Kristen; Earnshaw, Valerie A; Hansen, Nathan B; Kershaw, Trace S; Magnus, Manya; Krakower, Douglas S; Mayer, Kenneth H; Betancourt, Joseph R; Dovidio, John F

2016-07-01

Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting ("beneficiary") and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts.

A Closer Look at Racism and Heterosexism in Medical Students' Clinical Decision-Making Related to HIV Pre-Exposure Prophylaxis (PrEP): Implications for PrEP Education.

PubMed

Calabrese, Sarah K; Earnshaw, Valerie A; Krakower, Douglas S; Underhill, Kristen; Vincent, Wilson; Magnus, Manya; Hansen, Nathan B; Kershaw, Trace S; Mayer, Kenneth H; Betancourt, Joseph R; Dovidio, John F

2018-04-01

Social biases among healthcare providers could limit PrEP access. In this survey study of 115 US medical students, we examined associations between biases (racism and heterosexism) and PrEP clinical decision-making and explored prior PrEP education as a potential buffer. After viewing a vignette about a PrEP-seeking MSM patient, participants reported anticipated patient behavior (condomless sex, extra-relational sex, and adherence), intention to prescribe PrEP to the patient, biases, and background characteristics. Minimal evidence for racism affecting clinical decision-making emerged. In unadjusted analyses, heterosexism indirectly affected prescribing intention via all anticipated behaviors, tested as parallel mediators. Participants expressing greater heterosexism more strongly anticipated increased risk behavior and adherence problems, which were associated with lower prescribing intention. The indirect effect via condomless sex remained significant adjusting for background characteristics. Prior PrEP education did not buffer any indirect effects. Heterosexism may compromise PrEP provision to MSM and should be addressed in PrEP-related medical education.

Acceptability of Pre-Exposure Prophylaxis (PrEP) as an HIV prevention strategy: Barriers and facilitators to PrEP uptake among at-risk Peruvian populations

PubMed Central

Galea, Jerome T.; Kinsler, Janni J.; Salazar, Ximena; Lee, Sung-Jae; Giron, Maziel; Sayles, Jennifer N.; Cáceres, Carlos; Cunningham, William E.

2010-01-01

This study examined Pre-Exposure Prophylaxis (PrEP) acceptability among female sex workers, male-to-female transgendered persons, and men who have sex with men in Lima, Peru. Focus groups explored social issues associated with PrEP acceptability and conjoint analysis assessed preferences among eight hypothetical PrEP scenarios with varying attribute profiles and their relative impact on acceptability. Conjoint analysis revealed that PrEP acceptability ranged from 19.8 to 82.5 out of a possible score of 100 across the eight hypothetical PrEP scenarios. Out-of-pocket cost had the greatest impact on PrEP acceptability (25.2, p <0.001), followed by efficacy (21.4, p <0.001) and potential side effects (14.7, p <0.001). Focus group data supported these findings, and also revealed that potential sexual risk disinhibition, stigma and discrimination associated with PrEP use, and mistrust of health care professionals were also concerns. These issues will require careful attention when planning for PrEP roll-out if proven efficacious in ongoing clinical trials. PMID:21571973

Acceptability of Daily Use of Free Oral Pre-exposure Prophylaxis (PrEP) Among Transgender Women Sex Workers in Shenyang, China.

PubMed

Wang, Zixin; Lau, Joseph T F; Yang, Xueying; Cai, Yong; Gross, Danielle L; Ma, Tiecheng; Liu, Yan

2017-12-01

This study investigated the acceptability of daily use of free oral pre-exposure prophylaxis (PrEP) and associated factors among transgender women sex workers in Shenyang, China, following a briefing on PrEP. A total of 183 HIV negative or sero-status unknown participants completed the cross-sectional survey. The prevalence of acceptability of daily use of free oral PrEP was 61.2%. Adjusting for education level and monthly income, variables on negative attitudes toward PrEP (i.e., having concerns about the side-effects of PrEP) [Adjusted odds ratios (AOR): 0.26], perceived subjective norms (i.e., perceiving support from male partners to take PrEP) (AOR: 2.08), and perceived behavioral control (e.g., perceiving complete control over using PrEP) (AOR: 2.10-16.72) were significantly associated with acceptability of daily use of free oral PrEP. In addition, experiencing violence during sex work, perceived risk of contracting HIV from clients and probable anxiety were also significant. Future PrEP promotion campaigns should consider these factors.

PrPC has nucleic acid chaperoning properties similar to the nucleocapsid protein of HIV-1.

PubMed

Derrington, Edmund; Gabus, Caroline; Leblanc, Pascal; Chnaidermann, Jonas; Grave, Linda; Dormont, Dominique; Swietnicki, Wieslaw; Morillas, Manuel; Marck, Daniel; Nandi, Pradip; Darlix, Jean-Luc

2002-01-01

The function of the cellular prion protein (PrPC) remains obscure. Studies suggest that PrPC functions in several processes including signal transduction and Cu2+ metabolism. PrPC has also been established to bind nucleic acids. Therefore we investigated the properties of PrPC as a putative nucleic acid chaperone. Surprisingly, PrPC possesses all the nucleic acid chaperoning properties previously specific to retroviral nucleocapsid proteins. PrPC appears to be a molecular mimic of NCP7, the nucleocapsid protein of HIV-1. Thus PrPC, like NCP7, chaperones the annealing of tRNA(Lys) to the HIV-1 primer binding site, the initial step of retrovirus replication. PrPC also chaperones the two DNA strand transfers required for production of a complete proviral DNA with LTRs. Concerning the functions of NCP7 during budding, PrPC also mimices NCP7 by dimerizing the HIV-1 genomic RNA. These data are unprecedented because, although many cellular proteins have been identified as nucleic acid chaperones, none have the properties of retroviral nucleocapsid proteins.

Framing HIV Pre-Exposure Prophylaxis (PrEP) for the General Public: How Inclusive Messaging May Prevent Prejudice from Diminishing Public Support

PubMed Central

Calabrese, Sarah K.; Underhill, Kristen; Earnshaw, Valerie A.; Hansen, Nathan B.; Kershaw, Trace S.; Magnus, Manya; Krakower, Douglas S.; Mayer, Kenneth H.; Betancourt, Joseph R.; Dovidio, John F.

2016-01-01

Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting (“beneficiary”) and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts. PMID:26891840

Engaging with communities, engaging with patients: amendment to the NAPCRG 1998 Policy Statement on Responsible Research With Communities.

PubMed

Allen, Michele L; Salsberg, Jon; Knot, Michaela; LeMaster, Joseph W; Felzien, Maret; Westfall, John M; Herbert, Carol P; Vickery, Katherine; Culhane-Pera, Kathleen A; Ramsden, Vivian R; Zittleman, Linda; Martin, Ruth Elwood; Macaulay, Ann C

2017-06-01

In 1998, the North American Primary Care Research Group (NAPCRG) adopted a groundbreaking Policy Statement endorsing responsible participatory research (PR) with communities. Since that time, PR gained prominence in primary care research. To reconsider the original 1998 Policy Statement in light of increased uptake of PR, and suggest future directions and applications for PR in primary care. This work contributed to an updated Policy Statement endorsed by NAPCRG in 2015. 32 university and 30 community NAPCRG-affiliated research partners, convened a workshop to document lessons learned about implementing processes and principles of PR. This document emerged from that session and reflection and discussion regarding the original Policy Statement, the emerging PR literature, and our own experiences. The foundational principles articulated in the 1998 Policy Statement remain relevant to the current PR environment. Lessons learned since its publication include that the maturation of partnerships is facilitated by participatory processes that support increased community responsibility for research projects, and benefits generated through PR extend beyond research outcomes. Future directions that will move forward the field of PR in primary care include: (i) improve assessment of PR processes to better delineate the links between how PR teams work together and diverse PR outcomes, (ii) increase the number of models incorporating PR into translational research from project inception to dissemination, and (iii) increase application of PR approaches that support patient engagement in clinical settings to patient-provider relationship and practice change research. PR has markedly altered the manner in which primary care research is undertaken in partnership with communities and its principles and philosophies continue to offer means to assure that research results and processes improve the health of all communities. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Aortic valve calcification as a predictor of location and severity of paravalvular regurgitation after transcatheter aortic valve implantation.

PubMed

Koh, Ezra Y; Lam, Kayan Y; Bindraban, Navin R; Cocchieri, Riccardo; Planken, R Nils; Koch, Karel T; Baan, Jan; de Mol, Bas A; Marquering, Henk A

2015-03-01

To determine whether the location of aortic valve calcium (AVC) influences the location of paravalvular regurgitation (PR). PR is an adverse effect of transcatheter aortic valve implantation (TAVI) with a negative effect on long-term patient survival. The relationship between AVC and the occurrence of PR has been documented. However, the relationship between the distribution of AVC and the location of PR is still sparsely studied. The purpose of this study was to correlate severity and location of AVC with PR in patients treated with TAVI. Fifty-six consecutive patients who underwent transaortic or transapical TAVI and had preoperative computed tomography scans were included in this retrospective study. The volume, mass and location of AVC was determined and compared between patients with and without PR using a non-parametric t-test. Postoperative echocardiography was performed to determine the presence and location of PR, which was associated with the cusp with highest AVC using a χ(2) test. Valve deployment was successful in all 56 patients. PR was present in 38 patients (68%) after TAVI. There was a non-significantly higher volume of AVC in the PR group [214 (70-418) vs 371 (254-606) cm(3), P = 0.15]. AVC mass was significantly higher in patients with PR than in patients without PR [282 (188-421) vs 142 (48-259) mg, respectively, P = 0.043]. The location of PR was determined in 36 of these patients. Of these 36 patients, PR occurred at the cusp with the highest AVC in 20 patients (56%, χ(2) P = 0.030). In our population, PR was associated with greater AVC mass. Moreover, the location of PR was associated with the cusp with the highest amount of AVC. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Suppression of Murine Retrovirus Polypeptide Termination: Effect of Amber Suppressor tRNA on the Cell-Free Translation of Rauscher Murine Leukemia Virus, Moloney Murine Leukemia Virus, and Moloney Murine Sarcoma Virus 124 RNA

PubMed Central

Murphy, Edwin C.; Wills, Norma; Arlinghaus, Ralph B.

1980-01-01

The effect of suppressor tRNA's on the cell-free translation of several leukemia and sarcoma virus RNAs was examined. Yeast amber suppressor tRNA (amber tRNA) enhanced the synthesis of the Rauscher murine leukemia virus and clone 1 Moloney murine leukemia virus Pr200gag-pol polypeptides by 10- to 45-fold, but at the same time depressed the synthesis of Rauscher murine leukemia virus Pr65gag and Moloney murine leukemia virus Pr63gag. Under suppressor-minus conditions, Moloney murine leukemia virus Pr70gag was present as a closely spaced doublet. Amber tRNA stimulated the synthesis of the “upper” Moloney murine leukemia virus Pr70gag polypeptide. Yeast ochre suppressor tRNA appeared to be ineffective. Quantitative analyses of the kinetics of viral precursor polypeptide accumulation in the presence of amber tRNA showed that during linear protein synthesis, the increase in accumulated Moloney murine leukemia virus Pr200gag-pol coincided closely with the molar loss of Pr63gag. Enhancement of Pr200gag-pol and Pr70gag by amber tRNA persisted in the presence of pactamycin, a drug which blocks the initiation of protein synthesis, thus arguing for the addition of amino acids to the C terminus of Pr63gag as the mechanism behind the amber tRNA effect. Moloney murine sarcoma virus 124 30S RNA was translated into four major polypeptides, Pr63gag, P42, P38, and P23. In the presence of amber tRNA, a new polypeptide, Pr67gag, appeared, whereas Pr63gag synthesis was decreased. Quantitative estimates indicated that for every 1 mol of Pr67gag which appeared, 1 mol of Pr63gag was lost. Images PMID:7373716

Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

PubMed Central

Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-01-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

Recombinant human prion protein fragment 90-231, a useful model to study prion neurotoxicity.

PubMed

Corsaro, Alessandro; Thellung, Stefano; Villa, Valentina; Nizzari, Mario; Aceto, Antonio; Florio, Tullio

2012-01-01

Transmissible spongiform encephalopathies (TSE), or prion diseases, are a group of fatal neurodegenerative disorders of animals and humans. Human diseases include Creutzfeldt-Jakob (CJD) and Gerstmann-Straussler-Scheinker (GSSD) diseases, fatal familial insomnia, and Kuru. Human and animal TSEs share a common histopathology with a pathognomonic triad: spongiform vacuolation of the grey matter, neuronal death, glial proliferation, and, more inconstantly, amyloid deposition. According to the "protein only" hypothesis, TSEs are caused by a unique post-translational conversion of normal, host-encoded, protease-sensitive prion protein (PrP(sen) or PrP(C)) to an abnormal disease-associated isoform (PrP(res) or PrP(Sc)). To investigate the molecular mechanism of neurotoxicity induced by PrP(Sc) we developed a protocol to obtain millimolar amounts of soluble recombinant polypeptide encompassing the amino acid sequence 90-231 of human PrP (hPrP90-231). This protein corresponds to the protease-resistant prion protein fragment that originates after amino-terminal truncation. Importantly, hPrP90-231 has a flexible backbone that, similar to PrP(C), can undergo to structural rearrangement. This peptide, structurally resembling PrP(C), can be converted in a PrP(Sc)-like conformation, and thus represents a valuable model to study prion neurotoxicity. In this article we summarized our experimental evidence on the molecular and structural mechanisms responsible of hPrP90-231 neurotoxicity on neuroectodermal cell line SHSY5Y and the effects of some PrP pathogen mutations identified in familial TSE.

Adolescent Health Providers' Willingness to Prescribe Pre-Exposure Prophylaxis (PrEP) to Youth at Risk of HIV Infection in the United States.

PubMed

Hart-Cooper, Geoffrey D; Allen, Isabel; Irwin, Charles E; Scott, Hyman

2018-05-26

HIV disproportionately affects young men who have sex with men. Pre-exposure prophylaxis (PrEP) can prevent HIV acquisition; however, youth access to PrEP is limited by provider willingness to prescribe PrEP. We conducted an online survey of clinicians working with adolescents (aged 13-17 years) and young adults (aged 18-26 years) in the United States through the Society of Adolescent Health and Medicine. We used multivariate logistic regression to assess provider beliefs associated with willingness to provide PrEP. Nearly all (93.2%) providers had heard of PrEP, and 57 (35.2%) had prescribed PrEP. While almost all providers (95%) agreed that PrEP prevents HIV, fewer were willing to prescribe to young adults (77.8%) or adolescents (64.8%). Willingness to prescribe PrEP was strongly associated with the belief that providers had enough knowledge to safely provide PrEP to adolescents (OR 2.11, confidence interval [CI]: 1.18-3.76, p = .01) and young adults (odds ratio 5.19, CI: 2.15-12.50, p ≤ .001), and that adolescents would be adherent (odds ratio 3, CI: 1.30-6.90, p = .01). Response rate was 17%. Almost all providers had heard of PrEP and most providers were willing to prescribe PrEP. Provider education and tools to promote provider self-efficacy and adolescent adherence might improve provider willingness to provide PrEP. Copyright © 2018 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Dual modulation of ERK1/2 and p38 MAP kinase activities induced by minocycline reverses the neurotoxic effects of the prion protein fragment 90-231.

PubMed

Corsaro, Alessandro; Thellung, Stefano; Chiovitti, Katia; Villa, Valentina; Simi, Alessandro; Raggi, Federica; Paludi, Domenico; Russo, Claudio; Aceto, Antonio; Florio, Tullio

2009-02-01

Several in vitro and in vivo studies addressed the identification of molecular determinants of the neuronal death induced by PrP(Sc) or related peptides. We developed an experimental model to assess PrP(Sc) neurotoxicity using a recombinant polypeptide encompassing amino acids 90-231 of human PrP (hPrP90-231) that corresponds to the protease-resistant core of PrP(Sc) identified in prion-infected brains. By means of mild thermal denaturation, we can convert hPrP90-231 from a PrP(C)-like conformation into a PrP(Sc)-like structure. In virtue of these structural changes, hPrP90-231 powerfully affected the survival of SH-SY5Y cells, inducing caspase 3 and p38-dependent apoptosis, while in the native alpha-helix-rich conformation, hPrP90-231 did not induce cell toxicity. The aim of this study was to identify drugs able to block hPrP90-231 neurotoxic effects, focusing on minocycline, a tetracycline with known neuroprotective activity. hPrP90-231 caused a caspase 3-dependent apoptosis via the blockade of ERK1/2 activation and the subsequent activation of p38 MAP kinase. We propose that hPrP90-231-induced apoptosis is dependent on the inhibition of ERK1/2 responsiveness to neurotrophic factors, removing a tonic inhibition of p38 activity and resulting in caspase 3 activation. Minocycline prevented hPrP90-231-induced toxicity interfering with this mechanism: the pretreatment with this tetracycline restored ERK1/2 activity and reverted p38 and caspase 3 activities. The effects of minocycline were not mediated by the prevention of hPrP90-231 structural changes or cell internalization (differently from Congo Red). In conclusion, minocycline elicits anti-apoptotic effects against the neurotoxic activity of hPrP90-231 and these effects are mediated by opposite modulation of ERK1/2 and p38 MAP kinase activities.

Baseline Preferences for Daily, Event-Driven, or Periodic HIV Pre-Exposure Prophylaxis among Gay and Bisexual Men in the PRELUDE Demonstration Project.

PubMed

Vaccher, Stefanie J; Gianacas, Christopher; Templeton, David J; Poynten, Isobel M; Haire, Bridget G; Ooi, Catriona; Foster, Rosalind; McNulty, Anna; Grulich, Andrew E; Zablotska, Iryna B

2017-01-01

The effectiveness of daily pre-exposure prophylaxis (PrEP) is well established. However, there has been increasing interest in non-daily dosing schedules among gay and bisexual men (GBM). This paper explores preferences for PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project. Individuals at high-risk of HIV were enrolled in a free PrEP demonstration project in New South Wales, Australia, between November 2014 and April 2016. At baseline, they completed an online survey containing detailed behavioural, demographic, and attitudinal questions, including their ideal way to take PrEP: daily (one pill taken every day), event-driven (pills taken only around specific risk events), or periodic (daily dosing during periods of increased risk). Overall, 315 GBM (98% of study sample) provided a preferred PrEP dosing schedule at baseline. One-third of GBM expressed a preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for periodic PrEP. Individuals with a trade/vocational qualification were more likely to prefer periodic to daily PrEP [adjusted odds ratio (aOR) = 4.58, 95% confidence intervals (95% CI): (1.68, 12.49)], compared to individuals whose highest level of education was high school. Having an HIV-positive main regular partner was associated with strong preference for daily, compared to event-driven PrEP [aOR = 0.20, 95% CI: (0.04, 0.87)]. Participants who rated themselves better at taking medications were more likely to prefer daily over periodic PrEP [aOR = 0.39, 95% CI: (0.20, 0.76)]. Individuals' preferences for PrEP schedules are associated with demographic and behavioural factors that may impact on their ability to access health services and information about PrEP and patterns of HIV risk. At the time of data collection, there were limited data available about the efficacy of non-daily PrEP schedules, and clinicians only recommended daily PrEP to study participants. Further research investigating how behaviours and PrEP preferences change correspondingly over time is needed. ClinicalTrials.gov NCT02206555. Registered 28 July 2014.

Feasibility of noninvasive fetal electrocardiographic monitoring in a clinical setting.

PubMed

Arya, Bhawna; Govindan, Rathinaswamy; Krishnan, Anita; Duplessis, Adre; Donofrio, Mary T

2015-06-01

Cardiac rhythm is an essential component of fetal cardiac evaluation. The Monica AN24 is a fetal heart rate monitor that may provide a quick, inexpensive modality for obtaining a noninvasive fetal electrocardiogram (fECG) in a clinical setting. The fECG device has the ability to acquire fECG signals and allow calculation of fetal cardiac time intervals between 16- and 42-week gestational age (GA). We aimed to demonstrate the feasibility of fECG acquisition in a busy fetal cardiology clinic using the Monica fetal heart rate monitor. This is a prospective observational pilot study of fECG acquired from fetuses referred for fetal echocardiography. Recordings were performed for 5-15 min. Maternal signals were attenuated and fECG averaged. fECG and fetal cardiac time intervals (PR, QRS, RR, and QT) were evaluated by two cardiologists independently and inter-observer reliability was assessed using intraclass coefficient (ICC). Sixty fECGs were collected from 50 mothers (mean GA 28.1 ± 6.1). Adequate signal-averaged waveforms were obtained in 20 studies with 259 cardiac cycles. Waveforms could not be obtained between 26 and 30 weeks. Fetal cardiac time intervals were measured and were reproducible for PR (ICC = 0.89; CI 0.77-0.94), QRS (ICC = 0.79; CI 0.51-0.91), and RR (ICC = 0.77; CI 0.53-0.88). QT ICC was poor due to suboptimal T-wave tracings. Acquisition of fECG and measurement of fetal cardiac time intervals is feasible in a clinical setting between 19- and 42-week GA, though tracings are difficult to obtain, especially between 26 and 30 weeks. There was high reliability in fetal cardiac time intervals measurements, except for QT. The device may be useful for assessing atrioventricular/intraventricular conduction in fetuses from 20 to 26 and >30 weeks. Techniques to improve signal acquisition, namely T-wave amplification, are ongoing.

Phénomènes d'électrisation des matériaux isolants pour transformateurs de puissance

NASA Astrophysics Data System (ADS)

Peyraque, L.; Béroual, A.; Boisdon, C.; Buret, F.

1994-07-01

In power transformers, the oil flowed through the cooling ducts in coil assembly induces a static charge separation. The study of this static electrification phenomena is presented through a device allowing to investigate the charge separation generated by the rotating motion of a transformer pressboard in oil. This permits to show the influence of various parameters such as velocity, temperature, moisture and processing of oils and pressboards as well as their nature on this electrical charge. We also present another device allowing to classify oils according to their level of charge production. It appears from our results that a correlation exists between the density of these charges and the characteristics of oil such as conductivity, electric strength and water content. Dans les transformateurs de puissance, la circulation d'huile à travers les canaux de refroidissement en fibre cellulosique (carton isolant) est à l'origine d'une séparation de charges. L'étude de ce phénomène d'électrisation statique est présentée, tout d'abord à travers un dispositif permettant d'étudier la séparation de charges créées par le mouvement du carton dans l'huile. Celui-ci a permis de mettre en évidence l'influence de plusieurs paramètres comme la vitesse, la température, l'humidité et le traitement des huiles et cartons ainsi que la nature du carton sur cette charge. Le second dispositif présenté permet de classer les huiles selon leur niveau de création de charges. Une corrélation semble s'établir entre la densité de ces charges et les grandeurs caractéristiques de l'huile telles que la conductivité, la rigidité diélectrique et la teneur en eau.

Probing structural differences between PrPC and PrPSc by surface nitration and acetylation: evidence of conformational change in the C-terminus

USDA-ARS?s Scientific Manuscript database

We used two chemical modifiers, tetranitromethane (TNM) and acetic anhydride, which specifically target accessible tyrosine and lysine residues, respectively, to modify Syrian hamster recombinant PrP(90-231) (rPrP) and PrP27-30, aiming at finding locations of conformational change. Modified proteins...

Glass-Glass Transitions by Means of an Acceptor-Donor Percolating Electric-Dipole Network

NASA Astrophysics Data System (ADS)

Zhang, Le; Lou, Xiaojie; Wang, Dong; Zhou, Yan; Yang, Yang; Kuball, Martin; Carpenter, Michael A.; Ren, Xiaobing

2017-11-01

We report the ferroelectric glass-glass transitions in KN (K+/Nb5 +) -doped BaTiO3 ferroelectric ceramics, which have been proved by x-ray diffraction profile and Raman spectra data. The formation of glass-glass transitions can be attributed to the existence of cubic (C )-tetragonal (T )-orthorhombic (O )-rhombohedral (R ) ferroelectric transitions in short-range order. These abnormal glass-glass transitions can perform very small thermal hysteresis (approximately 1.0 K ) with a large dielectric constant (approximately 3000), small remanent polarization Pr , and relative high maximum polarization Pm remaining over a wide temperature range (220-350 K) under an electrical stimulus, indicating the potential applications in dielectric recoverable energy-storage devices with high thermal reliability. Further phase field simulations suggest that these glass-glass transitions are induced by the formation of a percolating electric defect-dipole network (PEDN). This proper PEDN breaks the long-range ordered ferroelectric domain pattern and results in the local phase transitions at the nanoscale. Our work may further stimulate the fundamental physical theory and accelerate the development of dielectric energy-storing devices.

The Combined Application of Impinger System and Permeation Tube for the Generation of Volatile Organic Compound Standard Gas Mixtures at Varying Diluent Flow Rates

PubMed Central

Kim, Ki-Hyun; Susaya, Janice; Cho, Jinwoo; Parker, David

2012-01-01

Commercial standard gas generators are often complex and expensive devices. The objective of this research was to assess the performance of a simplified glass impinger system for standard gas generation from a permeation tube (PT) device. The performance of the impinger standard gas generation system was assessed for four aromatic VOCs (benzene, toluene, ethylbenzene, and m-xylene; BTEX) at varying flow rates (FR) of 50 to 800 mL·min−1. Because actual permeation rate (APR) values deviated from those computed by the manufacturer's formula (MPR), new empirical relationships were developed to derive the predicted PR (PPR) of the target components. Experimental results corrected by such a formula indicate that the compatibility between the APR and MPR generally increased with low FR, while the reproducibility was generally reduced with decreasing flow rate. Although compatibility between different PRs is at a relatively small and narrow FR range, the use of correction formula is recommendable for the accurate use of PT. PMID:23112641

Gendered Differences in the Perceived Risks and Benefits of Oral PrEP Among HIV Serodiscordant Couples in Kenya

PubMed Central

Carroll, Jennifer J.; Ngure, Kenneth; Heffron, Renee; Curran, Kathryn; Mugo, Nelly R.

2016-01-01

Pre-exposure prophylaxis (PrEP) is effective for preventing HIV among HIV serodiscordant heterosexual couples. Gender roles may influence perceived personal and social risks related to HIV prevention behaviors and may affect use of PrEP. In this study, interviews and focus groups were conducted with 68 individuals from 34 mutually disclosed serodiscordant heterosexual partnerships in Thika, Kenya. Socio-cultural factors that affect adherence to PrEP were explored using grounded analysis. Three factors were identified, which shape perceptions of PrEP: gendered power dynamics and control over decision-making in the household; conflicts between risk reduction strategies and male sexual desire; culture bound definitions of women’s work. Adherence to PrEP in the Partners PrEP Study was high; however, participants articulated conflicting interests related to PrEP in connection with traditional gender roles. The successful delivery of PrEP will require understanding of key social factors, particularly related to gender and dyadic dynamics around HIV serostatus. PMID:26754017

Lifestyle Changes and Pressure Ulcer Prevention in Adults With Spinal Cord Injury in the Pressure Ulcer Prevention Study Lifestyle Intervention

PubMed Central

Ghaisas, Samruddhi; Pyatak, Elizabeth A.; Blanche, Erna; Clark, Florence

2015-01-01

Pressure ulcers (PrUs) are a major burden to patients with spinal cord injury (SCI), affecting their psychological, physical, and social well-being. Lifestyle choices are thought to contribute to the risk of developing PrUs. This article focuses on the interaction between lifestyle choices and the development of PrUs in community settings among participants in the University of Southern California–Rancho Los Amigos National Rehabilitation Center Pressure Ulcer Prevention Study (PUPS II), a randomized controlled trial of a lifestyle intervention for adults with SCI. We conducted a secondary cross-case analysis of treatment notes of 47 PUPS II participants and identified four patterns relating PrU development to lifestyle changes: positive PrU changes (e.g., healing PrUs) with positive lifestyle changes, negative or no PrU changes with positive lifestyle changes, positive PrU changes with minor lifestyle changes, and negative or no PrU changes with no lifestyle changes. We present case studies exemplifying each pattern. PMID:25553751

Applying a PrEP Continuum of Care for Men Who Have Sex With Men in Atlanta, Georgia

PubMed Central

Kelley, Colleen F.; Kahle, Erin; Siegler, Aaron; Sanchez, Travis; del Rio, Carlos; Sullivan, Patrick S.; Rosenberg, Eli S.

2015-01-01

Reductions in human immunodeficiency virus (HIV) incidence with pre-exposure prophylaxis (PrEP) for men who have sex with men (MSM) will require significant coverage of those at risk. We propose a simplified framework, similar to the HIV care continuum, to achieve protection with PrEP as follows: 1. At-risk MSM; 2. Awareness of and willingness to take PrEP; 3. Access to healthcare; 4. Receiving a prescription; and 5. Adhering to effective PrEP. We evaluated the PrEP care continuum on an Atlanta cohort of MSM and projected how many MSM might achieve protection from HIV. Even with optimistic estimates, few Atlanta MSM (15%) are projected to achieve protection from HIV with PrEP given the significant barriers described. Each continuum step represents an important point for intervention that could substantially increase the overall effectiveness of PrEP. In addition, novel strategies for PrEP delivery are needed to achieve the necessary effectiveness for Atlanta MSM at risk of HIV. PMID:26270691

Human FDC express PrPc in vivo and in vitro

PubMed Central

Thielen, Caroline; Antoine, Nadine; Mélot, France; Cesbron, Jean-Yves; Heinen, Ernst

2001-01-01

Prion diseases are fatal neurodegenerative disorders caused by accumulation of abnormal prion protein (protease-resistant prion, PrPres). PrPres accumulation is also detected in lymphoid organs after peripheral infection. Several studies suggest that follicular dendritic cells (FDC) could be the site of PrPres retention and amplification. Here we show that human follicular dendritic cells can express normal cellular prion protein (PrPc) both in situ and in vitro. When tonsillar cryosections were treated with anti-PrP antibody, the label was found on some very delicate cell extensions inside the lymphoid follicles, especially in the germinal centres. These extensions react with DRC1 antibody, used frequently to label FDC. Other structures labelled with anti-PrP antibody were the keratinocytes. To confirm the ability of FDC to synthesise PrPc, we isolated FDC by a non-enzymatic procedure and cultured them. By cytochemistry and flow cytometry it was clearly shown that FDC do produce PrPc. PMID:11785675

Incorporation of Pr into LuAG ceramics

NASA Astrophysics Data System (ADS)

Marchewka, M. R.; Chapman, M. G.; Qian, H.; Jacobsohn, L. G.

2017-06-01

An investigation of the effects of Pr in (Lu1-xPrx)3Al5O12 (LuAG:Pr) ceramics was carried out by means of x-ray diffraction (XRD), energy dispersive x-ray spectroscopy (EDX), and attenuated total reflection Fourier transform infrared spectroscopy (ATR FTIR) measurements coupled with luminescence measurements. It was found that the Pr concentration that maximizes luminescence emission depends on the thermal processing conditions. While the calcined LuAG:Pr powder showed maximum luminescence emission for Pr concentrations between 0.18 and 0.33 at.%, maximum emission of ceramic bodies sintered at 1500 °C for 20 h was obtained with Pr concentrations between 0.018 and 0.18 at.%. Further, for short sintering times up to about 3 h, luminescence emission intensity is maximum for Pr concentrations around 0.33 at.%. Longer sintering times lead to the formation of PrAlO3 as a secondary phase, concomitant with a reduction of the intensity of luminescence emission.

Acceptability of PrEP among HIV negative Portuguese men who have sex with men that attended 2014 Lisbon pride fair.

PubMed

Rocha, Luís Miguel; Campos, Maria José; Brito, João; Fuertes, Ricardo; Rojas, Jesus; Pinto, Nuno; Mendão, Luís; Esteves, Julio

2014-01-01

Consistent use of PrEP reduces HIV transmission from sexual practices amongst men who have sex with men (MSM) up to 92% [1]. Lisbon MSM cohort study estimates point that 59.3% of their participants at entrance (1593 HIV negative MSM enrolled between April 2011 and May 2013) were eligible for PrEP [2], according to the 2014 USA PrEP guidelines [3]. Studies about PrEP acceptability and implementation support policies aimed at increasing and rolling out its use. Hence, the exploratory study about PrEP acceptability in MSM at Lisbon. A street-based intercept survey, adapted from Mantell et al. study [4], was the one used on MSM attending the 2014 Lisbon pride fair. The survey included socio-demographic data, PrEP awareness and readiness to use it, probability of MSM's social network to also use it, promptness to join PrEP-related studies, type of PrEP warranted and condomless anal sex practice in the last six months. A total of 110 HIV negative Portuguese MSM responded, with a median age of 33% and 84% of them identified themselves as gay. A majority of MSM were unaware of PrEP (59%); those that were aware, had heard of it trough CheckpointLx (31%), internet (22%) or health professionals (20%). 66% were likely or very likely to participate in PrEP-related studies. 57% of MSM were likely or very likely to use PrEP if available and reported that some, if not almost all of their social network, will do it too (70%). Type of PrEP preferred was oral, a pill a day (43%), followed by oral, intermittent intake (32%). Overall 41% of MSM had condomless anal sex practice in the last six months. In this MSM Portuguese sample, a general willingness to adopt PrEP was predominant, specially the oral daily intake. Forty-one percent of participants had had condomless anal sex practice in the last six months and therefore fitted within the criteria to be on Pre-Exposure Prophylaxis (PrEP), according to MSM Risk Index in 2014 USA PrEP guidelines. PrEP, when available in Portugal, should be a powerful tool for HIV prevention in this key population.

Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation.

PubMed

Ross, Ian; Mejia, Carlos; Melendez, Johanna; Chan, Philip A; Nunn, Amy C; Powderly, William; Goodenberger, Katherine; Liu, Jingxia; Mayer, Kenneth H; Patel, Rupa R

2017-01-01

HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.

VLTI First Fringes with Two Auxiliary Telescopes at Paranal

NASA Astrophysics Data System (ADS)

2005-03-01

World's Largest Interferometer with Moving Optical Telescopes on Track Summary The Very Large Telescope Interferometer (VLTI) at Paranal Observatory has just seen another extension of its already impressive capabilities by combining interferometrically the light from two relocatable 1.8-m Auxiliary Telescopes. Following the installation of the first Auxiliary Telescope (AT) in January 2004 (see ESO PR 01/04), the second AT arrived at the VLT platform by the end of 2004. Shortly thereafter, during the night of February 2 to 3, 2005, the two high-tech telescopes teamed up and quickly succeeded in performing interferometric observations. This achievement heralds an era of new scientific discoveries. Both Auxiliary Telescopes will be offered from October 1, 2005 to the community of astronomers for routine observations, together with the MIDI instrument. By the end of 2006, Paranal will be home to four operational ATs that may be placed at 30 different positions and thus be combined in a very large number of ways ("baselines"). This will enable the VLTI to operate with enormous flexibility and, in particular, to obtain extremely detailed (sharp) images of celestial objects - ultimately with a resolution that corresponds to detecting an astronaut on the Moon. PR Photo 07a/05: Paranal Observing Platform with AT1 and AT2 PR Photo 07b/05: AT1 and AT2 with Open Domes PR Photo 07c/05: Evening at Paranal with AT1 and AT2 PR Photo 07d/05: AT1 and AT2 under the Southern Sky PR Photo 07e/05: First Fringes with AT1 and AT2 PR Video Clip 01/05: Two ATs at Paranal (Extract from ESO Newsreel 15) A Most Advanced Device ESO PR Video 01/05 ESO PR Video 01/05 Two Auxiliary Telescopes at Paranal [QuickTime: 160 x 120 pix - 37Mb - 4:30 min] [QuickTime: 320 x 240 pix - 64Mb - 4:30 min] ESO PR Photo 07a/05 ESO PR Photo 07a/05 [Preview - JPEG: 493 x400 pix - 44k] [Normal - JPEG: 985 x 800 pix - 727k] [HiRes - JPEG: 5000 x 4060 pix - 13.8M] Captions: ESO PR Video Clip 01/05 is an extract from ESO Video Newsreel 15, released on March 14, 2005. It provides an introduction to the VLT Interferometer (VLTI) and the two Auxiliary Telescopes (ATs) now installed at Paranal. ESO PR Photo 07a/05 shows the impressive ensemble at the summit of Paranal. From left to right, the enclosure of VLT Antu, Kueyen and Melipal, AT1, the VLT Survey Telescope (VST) in the background, AT2 and VLT Yepun. Located at the summit of the 2,600-m high Cerro Paranal in the Atacama Desert (Chile), ESO's Very Large Telescope (VLT) is at the forefront of astronomical technology and is one of the premier facilities in the world for optical and near-infrared observations. The VLT is composed of four 8.2-m Unit Telescope (Antu, Kueyen, Melipal and Yepun). They have been progressively put into service together with a vast suite of the most advanced astronomical instruments and are operated every night in the year. Contrary to other large astronomical telescopes, the VLT was designed from the beginning with the use of interferometry as a major goal. The href="/instruments/vlti">VLT Interferometer (VLTI) combines starlight captured by two 8.2- VLT Unit Telescopes, dramatically increasing the spatial resolution and showing fine details of a large variety of celestial objects. The VLTI is arguably the world's most advanced optical device of this type. It has already demonstrated its powerful capabilities by addressing several key scientific issues, such as determining the size and the shape of a variety of stars (ESO PR 22/02, PR 14/03 and PR 31/03), measuring distances to stars (ESO PR 25/04), probing the innermost regions of the proto-planetary discs around young stars (ESO PR 27/04) or making the first detection by infrared interferometry of an extragalactic object (ESO PR 17/03). "Little Brothers" ESO PR Photo 07b/05 ESO PR Photo 07b/05 [Preview - JPEG: 597 x 400 pix - 47k] [Normal - JPEG: 1193 x 800 pix - 330k] [HiRes - JPEG: 5000 x 3354 pix - 10.0M] ESO PR Photo 07c/05 ESO PR Photo 07c/05 [Preview - JPEG: 537 x 400 pix - 31k] [Normal - JPEG: 1074 x 800 pix - 555k] [HiRes - JPEG: 3000 x 2235 pix - 6.0M] ESO PR Photo 07d/05 ESO PR Photo 07d/05 [Preview - JPEG: 400 x 550 pix - 60k] [Normal - JPEG: 800 x 1099 pix - 946k] [HiRes - JPEG: 2414 x 3316 pix - 11.0M] Captions: ESO PR Photo 07b/05 shows VLTI Auxiliary Telescopes 1 and 2 (AT1 and AT2) in the early evening light, with the spherical domes opened and ready for observations. In ESO PR Photo 07c/05, the same scene is repeated later in the evening, with three of the large telescope enclosures in the background. This photo and ESO PR Photo 07c/05 which is a time-exposure with AT1 and AT2 under the beautiful night sky with the southern Milky Way band were obtained by ESO staff member Frédéric Gomté. However, most of the time the large telescopes are used for other research purposes. They are therefore only available for interferometric observations during a limited number of nights every year. Thus, in order to exploit the VLTI each night and to achieve the full potential of this unique setup, some other (smaller), dedicated telescopes were included into the overall VLT concept. These telescopes, known as the VLTI Auxiliary Telescopes (ATs), are mounted on tracks and can be placed at precisely defined "parking" observing positions on the observatory platform. From these positions, their light beams are fed into the same common focal point via a complex system of reflecting mirrors mounted in an underground system of tunnels. The Auxiliary Telescopes are real technological jewels. They are placed in ultra-compact enclosures, complete with all necessary electronics, an air conditioning system and cooling liquid for thermal control, compressed air for enclosure seals, a hydraulic plant for opening the dome shells, etc. Each AT is also fitted with a transporter that lifts the telescope and relocates it from one station to another. It moves around with its own housing on the top of Paranal, almost like a snail. Moreover, these moving ultra-high precision telescopes, each weighing 33 tonnes, fulfill very stringent mechanical stability requirements: "The telescopes are unique in the world", says Bertrand Koehler, the VLTI AT Project Manager. "After being relocated to a new position, the telescope is repositioned to a precision better than one tenth of a millimetre - that is, the size of a human hair! The image of the star is stabilized to better than thirty milli-arcsec - this is how we would see an object of the same size as one of the VLT enclosures on the Moon. Finally, the path followed by the light inside the telescope after bouncing on ten mirrors is stable to better than a few nanometres, which is the size of about one hundred atoms." A World Premiere ESO PR Photo 07e/05 ESO PR Photo 07e/05 "First Fringes" with two ATs [Preview - JPEG: 400 x 559 pix - 61k] [Normal - JPEG: 800 x 1134 pix - 357k] Caption: ESO PR Photo 07e/05 The "First Fringes" obtained with the first two VLTI Auxiliary Telescopes, as seen on the computer screen during the observation. The fringe pattern arises when the light beams from the two 1.8-m telescopes are brought together inside the VINCI instrument. The pattern itself contains information about the angular extension of the observed object, here the 6th-magnitude star HD62082. The fringes are acquired by moving a mirror back and forth around the position of equal path length for the two telescopes. One such scan can be seen in the third row window. This pattern results from the raw interferometric signals (the last two rows) after calibration and filtering using the photometric signals (the 4th and 5th row). The first two rows show the spectrum of the fringe pattern signal. More details about the interpretation of this pattern is given in Appendix A of PR 06/01. The possibility to move the ATs around and thus to perform observations with a large number of different telescope configurations ensures a great degree of flexibility, unique for an optical interferometric installation of this size and crucial for its exceptional performance. The ATs may be placed at 30 different positions and thus be combined in a very large number of ways. If the 8.2-m VLT Unit Telescopes are also taken into account, no less than 254 independent pairings of two telescopes ("baselines"), different in length and/or orientation, are available. Moreover, while the largest possible distance between two 8.2-m telescopes (ANTU and YEPUN) is about 130 metres, the maximal distance between two ATs may reach 200 metres. As the achievable image sharpness increases with telescope separation, interferometric observations with the ATs positioned at the extreme positions will therefore yield sharper images than is possible by combining light from the large telescopes alone. All of this will enable the VLTI to obtain exceedingly detailed (sharp) and very complete images of celestial objects - ultimately with a resolution that corresponds to detecting an astronaut on the Moon. Auxiliary Telescope no. 1 (AT1) was installed on the observatory's platform in January 2004. Now, one year later, the second of the four to be delivered, has been integrated into the VLTI. The installation period lasted two months and ended around midnight during the night of February 2-3, 2005. With extensive experience from the installation of AT1, the team of engineers and astronomers were able to combine the light from the two Auxiliary Telescopes in a very short time. In fact, following the necessary preparations, it took them only five minutes to adjust this extremely complex optical system and successfully capture the "First Fringes" with the VINCI test instrument! The star which was observed is named HD62082 and is just at the limit of what can be observed with the unaided eye (its visual magnitude is 6.2). The fringes were as clear as ever, and the VLTI control system kept them stable for more than one hour. Four nights later this exercise was repeated successfully with the mid-infrared science instrument MIDI. Fringes on the star Alphard (Alpha Hydrae) were acquired on February 7 at 4:05 local time. For Roberto Gilmozzi, Director of ESO's La Silla Paranal Observatory, "this is a very important new milestone. The introduction of the Auxiliary Telescopes in the development of the VLT Interferometer will bring interferometry out of the specialist experiment and into the domain of common user instrumentation for every astronomer in Europe. Without doubt, it will enormously increase the potentiality of the VLTI." With two more telescopes to be delivered within a year to the Paranal Observatory, ESO cements its position as world-leader in ground-based optical astronomy, providing Europe's scientists with the tools they need to stay at the forefront in this exciting science. The VLT Interferometer will, for example, allow astronomers to study details on the surface of stars or to probe proto-planetary discs and other objects for which ultra-high precision imaging is required. It is premature to speculate on what the Very Large Telescope Interferometer will soon discover, but it is easy to imagine that there may be quite some surprises in store for all of us.

Proteasome inhibitors promote the sequestration of PrPSc into aggresomes within the cytosol of prion-infected CAD neuronal cells.

PubMed

Dron, Michel; Dandoy-Dron, Françoise; Farooq Salamat, Muhammad Khalid; Laude, Hubert

2009-08-01

Dysfunction of the endoplasmic reticulum associated protein degradation/proteasome system is believed to contribute to the initiation or aggravation of neurodegenerative disorders associated with protein misfolding, and there is some evidence to suggest that proteasome dysfunctions might be implicated in prion disease. This study investigated the effect of proteasome inhibitors on the biogenesis of both the cellular (PrP(C)) and abnormal (PrP(Sc)) forms of prion protein in CAD neuronal cells, a newly introduced prion cell system. In uninfected cells, proteasome impairment altered the intracellular distribution of PrP(C), leading to a strong accumulation in the Golgi apparatus. Moreover, a detergent-insoluble and weakly protease-resistant PrP species of 26 kDa, termed PrP(26K), accumulated in the cells, whether they were prion-infected or not. However, no evidence was found that, in infected cells, this PrP(26K) species converts into the highly proteinase K-resistant PrP(Sc). In the infected cultures, proteasome inhibition caused an increased intracellular aggregation of PrP(Sc) that was deposited into large aggresomes. These findings strengthen the view that, in neuronal cells expressing wild-type PrP(C) from the natural promoter, proteasomal impairment may affect both the process of PrP(C) biosynthesis and the subcellular sites of PrP(Sc) accumulation, despite the fact that these two effects could essentially be disconnected.

When and why women might suspend PrEP use according to perceived seasons of risk: implications for PrEP-specific risk-reduction counselling

PubMed Central

Namey, Emily; Agot, Kawango; Ahmed, Khatija; Odhiambo, Jacob; Skhosana, Joseph; Guest, Greg; Corneli, Amy

2016-01-01

Oral pre-exposure prophylaxis (PrEP) using the antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada) has been shown to dramatically reduce the risk of HIV acquisition for women at higher risk of infection if taken daily. Understanding when and why women would intentionally stop using an efficacious oral PrEP drug within the context of their “normal” daily lives is essential for delivering effective PrEP risk-reduction counselling. We conducted 60 qualitative interviews with women at higher risk of HIV in Bondo, Kenya, and Pretoria, South Africa, as part of a larger study. Participants charted their sexual contacts over the previous six months, indicated whether they would have taken PrEP if available, and discussed whether and why they would have suspended PrEP use. Nearly all participants said they would have used PrEP in the previous six months; half indicated they would have suspended PrEP use at some point. Participants’ reasons for an extended break from PrEP were related to partnership dynamics (e.g., perceived low risk of a stable partner) and phases of life (e.g., trying to conceive). Life events (e.g., holidays and travel) could prompt shorter breaks in PrEP use. These circumstances may or may not correspond to actual contexts of lower risk, highlighting the importance of tailored PrEP risk-reduction counselling. PMID:27093238

Lessons learned from the experiences of informal PrEP users in France: results from the ANRS-PrEPage study.

PubMed

Rivierez, I; Quatremere, G; Spire, B; Ghosn, J; Rojas Castro, D

2018-05-30

Before January 2016, Pre-Exposure Prophylaxis (PrEP), a new biomedical HIV-prevention tool, was only available in France via ANRS-Ipergay clinical study but informal use was reported outside this setting. PrEPage qualitative study reports profiles and experiences of participants who used PrEP outside of a biomedical trial before this prevention method was authorized. Between March 2015 and February 2016, a cross-section of twenty-four informal PrEP users, mostly MSM, was recruited to complete in-depth semi-structured interviews. While ANRS-Ipergay was still ongoing (2012-2016), participants described their initiation to PrEP, the way they used it and the difficulties they faced to acquire antiretroviral drugs in an environment where PrEP was still not widely known and often criticized . Through the testimonies, different user profiles and motivation toward informal PrEP use emerged: (a) participants who have increasing difficulties using condoms, (b) "opportunists" who tried PrEP without the intention of using it regularly and (c) participants with a risk aversion who sought additional protection against HIV. Participants chose to use PrEP and/or their usual prevention strategies depending on available supplies, type of partners and individual attitudes toward risk. The feeling of living a safer sex life helped participants to outweigh the fear of possible toxicity and drug resistance. Participants' needs and expectations about PrEP implementation in France were also presented.

PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells.

PubMed

Llorens, Franc; Carulla, Patricia; Villa, Ana; Torres, Juan M; Fortes, Puri; Ferrer, Isidre; del Río, José A

2013-10-01

The prion protein (PrP) plays a key role in prion disease pathogenesis. Although the misfolded and pathologic variant of this protein (PrP(SC)) has been studied in depth, the physiological role of PrP(C) remains elusive and controversial. PrP(C) is a cell-surface glycoprotein involved in multiple cellular functions at the plasma membrane, where it interacts with a myriad of partners and regulates several intracellular signal transduction cascades. However, little is known about the gene expression changes modulated by PrP(C) in animals and in cellular models. In this article, we present PrP(C)-dependent gene expression signature in N2a cells and its implication in the most overrepresented functions: cell cycle, cell growth and proliferation, and maintenance of cell shape. PrP(C) over-expression enhances cell proliferation and cell cycle re-entrance after serum stimulation, while PrP(C) silencing slows down cell cycle progression. In addition, MAP kinase and protein kinase B (AKT) pathway activation are under the regulation of PrP(C) in asynchronous cells and following mitogenic stimulation. These effects are due in part to the modulation of epidermal growth factor receptor (EGFR) by PrP(C) in the plasma membrane, where the two proteins interact in a multimeric complex. We also describe how PrP(C) over-expression modulates filopodia formation by Rho GTPase regulation mainly in an AKT-Cdc42-N-WASP-dependent pathway. © 2013 International Society for Neurochemistry.

Winter diversity and expression of proteorhodopsin genes in a polar ocean

PubMed Central

Nguyen, Dan; Maranger, Roxane; Balagué, Vanessa; Coll-Lladó, Montserrat; Lovejoy, Connie; Pedrós-Alió, Carlos

2015-01-01

Mixotrophy is a valuable functional trait used by microbes when environmental conditions vary broadly or resources are limited. In the sunlit waters of the ocean, photoheterotrophy, a form of mixotrophy, is often mediated by proteorhodopsin (PR), a seven helices transmembrane protein binding the retinal chromophore. Altogether, they allow bacteria to capture photic energy for sensory and proton gradient formation cell functions. The seasonal occurrence and diversity of the gene coding for PR in cold oligotrophic polar oceans is not known and PR expression has not yet been reported. Here we show that PR is widely distributed among bacterial taxa, and that PR expression decreased markedly during the winter months in the Arctic Ocean. Gammaproteobacteria-like PR sequences were always dominant. However, within the second most common affiliation, there was a transition from Flavobacteria-like PR in early winter to Alphaproteobacteria-like PR in late winter. The phylogenetic shifts followed carbon dynamics, where patterns in expression were consistent with community succession, as identified by DNA community fingerprinting. Although genes for PR were always present, the trend in decreasing transcripts from January to February suggested reduced functional utility of PR during winter. Under winter darkness, sustained expression suggests that PR may continue to be useful for non-ATP forming functions, such as environmental sensing or small solute transport. The persistence of PR expression in winter among some bacterial groups may offer a competitive advantage, where its multifunctionality enhances microbial survival under harsh polar conditions. PMID:25700336

Winter diversity and expression of proteorhodopsin genes in a polar ocean.

PubMed

Nguyen, Dan; Maranger, Roxane; Balagué, Vanessa; Coll-Lladó, Montserrat; Lovejoy, Connie; Pedrós-Alió, Carlos

2015-08-01

Mixotrophy is a valuable functional trait used by microbes when environmental conditions vary broadly or resources are limited. In the sunlit waters of the ocean, photoheterotrophy, a form of mixotrophy, is often mediated by proteorhodopsin (PR), a seven helices transmembrane protein binding the retinal chromophore. Altogether, they allow bacteria to capture photic energy for sensory and proton gradient formation cell functions. The seasonal occurrence and diversity of the gene coding for PR in cold oligotrophic polar oceans is not known and PR expression has not yet been reported. Here we show that PR is widely distributed among bacterial taxa, and that PR expression decreased markedly during the winter months in the Arctic Ocean. Gammaproteobacteria-like PR sequences were always dominant. However, within the second most common affiliation, there was a transition from Flavobacteria-like PR in early winter to Alphaproteobacteria-like PR in late winter. The phylogenetic shifts followed carbon dynamics, where patterns in expression were consistent with community succession, as identified by DNA community fingerprinting. Although genes for PR were always present, the trend in decreasing transcripts from January to February suggested reduced functional utility of PR during winter. Under winter darkness, sustained expression suggests that PR may continue to be useful for non-ATP forming functions, such as environmental sensing or small solute transport. The persistence of PR expression in winter among some bacterial groups may offer a competitive advantage, where its multifunctionality enhances microbial survival under harsh polar conditions.

Binding characteristics of the ovine membrane progesterone receptor alpha and expression of the receptor during the estrous cycle

PubMed Central

Ashley, Ryan L; Arreguin-Arevalo, J Alejandro; Nett, Terry M

2009-01-01

Background Classically, progesterone has been thought to act only through the well-known genomic pathway involving hormone binding to nuclear receptors and subsequent modulation of gene expression. However, there is increasing evidence for rapid, non-genomic effects of progesterone in a variety of mammalian tissues and it is possible that a membrane PR (mPR) is causing these events. We recently isolated and characterized an ovine mPR referred to as mPR-alpha, distinct from the nuclear PR. Based on predicted structural analysis, the ovine mPR-alpha possesses seven transmembrane domains typical of G protein-coupled receptors. Despite the homology to other reported mPRs, information pertaining to the steroid binding characteristics of the ovine mPR-alpha was lacking. Additionally, the ovine mPR-alpha transcript has been identified in the hypothalamus, pituitary, uterus, ovary and corpus luteum, yet changes in expression of the ovine mPR-alpha in these tissues were not known. Consequently, the purpose of this work was to determine the steroid binding characteristics of the ovine mPR-alpha and to investigate possible changes in expression of the ovine mPR-alpha in reproductive tissues throughout the estrous cycle. Methods Binding studies were performed using crude membrane fractions from CHO cells expressing the mPR-alpha. Using quantitative Real-time PCR we determined the expression pattern of mRNA for the ovine mPR-alpha during the ovine estrous cycle in tissues known to express the mPR-alpha. Jugular blood samples were also collected and analyzed for serum concentrations of P4 to ensure ewes were at the appropriate stage of their cycle. Results Only progesterone, 20alpha-hydroxyprogesterone and 17alpha-hydroxyprogesterone were able to displace binding of 3H-P4 (P < 0.001) to membrane fractions from CHO cells expressing ovine mPR-alpha. The average B-max and Kd values for three separate experiments were 624 +/- 119 fmol/micro gram protein and 122 +/- 50 nM, respectively. Significant changes in expression of mRNA for the mPR-alpha during the estrous cycle were noted in the corpus luteum and uterus. Conclusion The mPR-alpha specifically binds progestins and its expression was correlated to progesterone secretion during the ovine estrous cycle. Results from the present studies suggest that mPR-alpha may have an important physiological role during the ovine estrous cycle. PMID:19432978

Role of nuclear progesterone receptor isoforms in uterine pathophysiology

PubMed Central

Patel, Bansari; Elguero, Sonia; Thakore, Suruchi; Dahoud, Wissam; Bedaiwy, Mohamed; Mesiano, Sam

2015-01-01

BACKGROUND Progesterone is a key hormonal regulator of the female reproductive system. It plays a major role to prepare the uterus for implantation and in the establishment and maintenance of pregnancy. Actions of progesterone on the uterine tissues (endometrium, myometrium and cervix) are mediated by the combined effects of two progesterone receptor (PR) isoforms, designated PR-A and PR-B. Both receptors function primarily as ligand-activated transcription factors. Progesterone action on the uterine tissues is qualitatively and quantitatively determined by the relative levels and transcriptional activities of PR-A and PR-B. The transcriptional activity of the PR isoforms is affected by specific transcriptional coregulators and by PR post-translational modifications that affect gene promoter targeting. In this context, appropriate temporal and cell-specific expression and function of PR-A and PR-B are critical for normal uterine function. METHODS Relevant studies describing the role of PRs in uterine physiology and pathology (endometriosis, uterine leiomyoma, endometrial cancer, cervical cancer and recurrent pregnancy loss) were comprehensively searched using PubMed, Cochrane Library, Web of Science, and Google Scholar and critically reviewed. RESULTS Progesterone, acting through PR-A and PR-B, regulates the development and function of the endometrium and induces changes in cells essential for implantation and the establishment and maintenance of pregnancy. During pregnancy, progesterone via the PRs promotes myometrial relaxation and cervical closure. Withdrawal of PR-mediated progesterone signaling triggers menstruation and parturition. PR-mediated progesterone signaling is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen on eutopic normal endometrium, and on ectopic implants in endometriosis. Similarly, ligand-activated PRs function as tumor suppressors in endometrial cancer cells through inhibition of key cellular signaling pathways required for growth. In contrast, progesterone via PR activation appears to increase leiomyoma growth. The exact role of PRs in cervical cancer is unclear. PRs regulate implantation and therefore aberrant PR function may be implicated in recurrent pregnancy loss (RPL). PRs likely regulate key immunogenic factors involved in RPL. However, the exact role of PRs in the pathophysiology of RPL and the use of progesterone for therapeutic benefit remains uncertain. CONCLUSIONS PRs are key mediators of progesterone action in uterine tissues and are essential for normal uterine function. Aberrant PR function (due to abnormal expression and/or function) is a major cause of uterine pathophysiology. Further investigation of the underlying mechanisms of PR isoform action in the uterus is required, as this knowledge will afford the opportunity to create progestin/PR-based therapeutics to treat various uterine pathologies. PMID:25406186

Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simian, Marina; Bissell, Mina J.; Barcellos-Hoff, Mary Helen

2009-05-11

Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics. We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levelsmore » of latency-associated peptide and transforming growth factor beta 1 (TGF{beta}1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography. The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGF{beta}1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice. These data establish a link between hormonal response, proliferation, modulation of MMP activity and maintenance of basement membrane integrity that depend on a balance in the expression levels of PR-A and PR-B isoforms. Notably, concomitant increased proliferation, due to inhibition of TGF{beta}1 activation, and loss of basement membrane integrity, via increased MMP-2 activity, appear to be prerequisites for the PR-A hyperplastic phenotype.« less

75 FR 53963 - Notice of Baseline Filings: The Peoples Gas Light and Coke Company, Minnesota Energy Resources...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-86-000, Docket No. PR10-87-000, Docket No. PR10-88- 000, Docket No. PR10-89-000, Docket No. PR10-90-000] Notice of Baseline Filings: The Peoples Gas Light and Coke Company, Minnesota Energy Resources Corporation, Louisville Gas...

Novel epitopes identified by Anti-PrP monoclonal antibodies produced following immunization of Prnp0/0 Balb/cJ mice with purified scrapie prions

USDA-ARS?s Scientific Manuscript database

Prions, or infectious proteins, cause a class of uniformly fatal neurodegenerative diseases. Prions are composed solely of an aberrantly folded isoform(PrPSc)of a normal cellular protein (PrPC). Shared sequence identity of PrPSc with PrPC has limited the detection sensitivity of immunochemical assay...

Expression and Functional Characterization of two Pathogenesis-Related Protein 10 Genes from Zea mays

USDA-ARS?s Scientific Manuscript database

Pathogenesis-related protein 10 (PR10) is one of seventeen PR protein families and plays important roles in plant response to biotic and abiotic stresses. A novel PR10 gene (ZmPR10.1), which shares 89.8% and 85.7% identity to the previous ZmPR10 at the nucleotide and amino acid sequence level, respe...

Understanding the Press Kit and Its Use by the Media: When PR Material Becomes News

ERIC Educational Resources Information Center

Weisgerber, Corinne

2006-01-01

This activity helps students understand the relationship between public relations (PR) writing and news writing by demonstrating how PR material gets used in the production of news stories. Considering that "more than 70 percent of daily newspaper copy emanates from PR-generated releases," it is important for students to learn how PR professionals…

Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates*

PubMed Central

Margalith, Ilan; Suter, Carlo; Ballmer, Boris; Schwarz, Petra; Tiberi, Cinzia; Sonati, Tiziana; Falsig, Jeppe; Nyström, Sofie; Hammarström, Per; Åslund, Andreas; Nilsson, K. Peter R.; Yam, Alice; Whitters, Eric; Hornemann, Simone; Aguzzi, Adriano

2012-01-01

Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23–231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23–231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits. PMID:22493452

Prion propagation in cells expressing PrP glycosylation mutants.

PubMed

Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-04-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

Neutrophil elastase and proteinase 3 trafficking routes in myelomonocytic cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaellquist, Linda; Rosen, Hanna; Nordenfelt, Pontus

2010-11-15

Neutrophil elastase (NE) and proteinase 3 (PR3) differ in intracellular localization, which may reflect different trafficking mechanisms of the precursor forms when synthesized at immature stages of neutrophils. To shed further light on these mechanisms, we compared the trafficking of precursor NE (proNE) and precursor PR3 (proPR3). Like proNE [1], proPR3 interacted with CD63 upon heterologous co-expression in COS cells but endogenous interaction was not detected although cell surface proNE/proPR3/CD63 were co-endocytosed in myelomonocytic cells. Cell surface proNE/proPR3 turned over more rapidly than cell surface CD63 consistent with processing/degradation of the pro-proteases but recycling of CD63. Colocalization of proNE/proPR3/CD63 withmore » clathrin and Rab 7 suggested trafficking through coated vesicles and late endosomes. Partial caveolar trafficking of proNE/CD63 but not proPR3 was suggested by colocalization with caveolin-1. Blocking the C-terminus of proNE/proPR3 by creating a fusion with FK506 binding protein inhibited endosomal re-uptake of proNE but not proPR3 indicating 'pro{sub C}'-peptide-dependent structural/conformational requirements for proNE but not for proPR3 endocytosis. The NE aminoacid residue Y199 of a proposed NE sorting motif that interacts with AP-3 [2] was not required for proNE processing, sorting or endocytosis in rat basophilic leukemia (RBL) cells expressing heterologous Y199-deleted proNE; this suggests operation of another AP-3-link for proNE targeting. Our results show intracellular multi-step trafficking to be different between proNE and proPR3 consistent with their differential subcellular NE/PR3 localization in neutrophils.« less

Cognitive Remediation in Middle-Aged or Older Inpatients with Chronic Schizophrenia: A Randomized Controlled Trial in Korea.

PubMed

Choi, Kee-Hong; Kang, Jinsook; Kim, Sun-Min; Lee, Seung-Hwan; Park, Seon-Cheol; Lee, Won-Hye; Choi, Sun; Park, Kiho; Hwang, Tae-Yeon

2017-01-01

Background: Accumulating evidence indicates that cognitive remediation (CR) is effective for improving various cognitive deficits in adult patients with schizophrenia. Although reports of brain plasticity in older adults and the service needs for chronic patients with schizophrenia are increasing, very few randomized controlled trials of CR have been conducted in middle-aged or older inpatients with chronic schizophrenia. We investigated the efficacy of individualized CR on the cognitive impairments of middle-aged or older inpatients with chronic schizophrenia within the context of comprehensive psychiatric rehabilitation (PR) by comparing the results obtained with PR only and treatment as usual (TAU). Method: Fifty-seven middle-aged and older individuals with chronic schizophrenia and mild to moderate cognitive deficits were enrolled. Thirty-eight who were undergoing PR were randomly assigned to CR + PR ( N = 19) or PR-only ( N = 19) groups. Nineteen participants who were undergoing TAU without CR or PR were evaluated pre- and post-treatment. Results: CR was easily provided and well received (drop-out rates = 5.3%) by middle-aged or older psychiatric inpatients. Compared to the PR-Only or TAU patients, patients in the CR + PR group showed greater improvement in executive functioning. Compared to TAU patients, CR + PR and PR-only patients showed greater improvement in logical memory. More patients in the CR + PR group improved clinically significantly in executive functioning and logical memory, compared with the PR-only and TAU patients. Conclusions: These results suggested that CR improved some cognitive deficits in middle-aged or older inpatients with chronic schizophrenia and that it was effective as an adjunctive treatment to the usual PR services provided in inpatient settings. Clinical Registration: KCT0002609.

Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II).

PubMed

Zeuzem, S; Flisiak, R; Vierling, J M; Mazur, W; Mazzella, G; Thongsawat, S; Abdurakhmanov, D; Van Kính, N; Calistru, P; Heo, J; Stanciu, C; Gould, M; Makara, M; Hsu, S-J; Buggisch, P; Samuel, D; Mutimer, D; Nault, B; Merz, M; Bao, W; Griffel, L H; Brass, C; Naoumov, N V

2015-10-01

Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens. © 2015 John Wiley & Sons Ltd.

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms.

PubMed

Tsigkou, Anastasia; Reis, Fernando M; Lee, Meng H; Jiang, Bingjie; Tosti, Claudia; Centini, Gabriele; Shen, Fang-Rong; Chen, You-Guo; Petraglia, Felice

2015-07-01

To investigate the possible correlation between progesterone receptor (PR) expression in uterine leiomyoma or adjacent myometrium and patient's age, size/number of leiomyomas, or clinical symptoms such as dysmenorrhea, acyclic pelvic pain, or menstrual and intermenstrual uterine bleeding. Cross-sectional study. Referral center. Sixty-two Chinese women undergoing elective hysterectomy for uterine leiomyomata. None. Evaluation of PR-total and PR-B mRNA with real-time polymerase chain reaction; PR-A and PR-B proteins quantified by Western blot in leiomyoma tissue and myometrium; symptoms rated by the patients using visual analog scores. The PR-B mRNA and PR-A and PR-B proteins were more concentrated in leiomyomas than in matched myometrium. A direct correlation between PR-B mRNA levels in leiomyoma and age (r = 0.347) and number of tumors (r = 0.295) was found. Conversely, there was an inverse correlation between PR-B mRNA levels in leiomyoma and dysmenorrhea (r = -0.260) and intermenstrual bleeding (r = -0.266). Multiple regression analysis indicated that age (β = 0.363) and the number of myomas (β = 0.296) were independently associated with PR-B mRNA levels in leiomyoma tissue. The levels of PR-B mRNA in leiomyoma tissue are directly associated with the number of tumors and inversely correlated with the intensity of intermenstrual bleeding and dysmenorrhea, suggesting that PR signaling may favor leiomyoma growth while attenuating clinical symptoms. This duality should be taken into account in the clinical management of patients with symptomatic uterine leiomyoma. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Diversity in genomic organisation, developmental regulation and distribution of the murine PR72/B" subunits of protein phosphatase 2A

PubMed Central

Zwaenepoel, Karen; Louis, Justin V; Goris, Jozef; Janssens, Veerle

2008-01-01

Background Protein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways. PP2A holoenzymes comprise a core dimer composed of a catalytic C and a structural A subunit, which can associate with a variable B-type subunit. The importance of the B-type subunits for PP2A regulation cannot be overestimated as they determine holoenzyme localisation, activity and substrate specificity. Three B-type subunit families have been identified: PR55/B, PR61/B' and PR72/B", of which the latter is currently the least characterised. Results We deduced the sequences and genomic organisation of the different murine PR72/B" isoforms: three genes encode nine isoforms, five of which are abundantly expressed and give rise to genuine PP2A subunits. Thereby, one novel subunit was identified. Using Northern blotting, we examined the tissue-specific and developmental expression of these subunits. All subunits are highly expressed in heart, suggesting an important cardiac function. Immunohistochemical analysis revealed a striated expression pattern of PR72 and PR130 in heart and skeletal muscle, but not in bladder smooth muscle. The subcellular localisation and cell cycle regulatory ability of several PR72/B" isoforms were determined, demonstrating differences as well as similarities. Conclusion In contrast to PR55/B and PR61/B', the PR72/B" family seems evolutionary more divergent, as only two of the murine genes have a human orthologue. We have integrated these results in a more consistent nomenclature of both human and murine PR72/B" genes and their transcripts/proteins. Our results provide a platform for the future generation of PR72/B" knockout mice. PMID:18715506

The Physical Relationship between Infectivity and Prion Protein Aggregates Is Strain-Dependent

PubMed Central

Tixador, Philippe; Herzog, Laëtitia; Reine, Fabienne; Jaumain, Emilie; Chapuis, Jérôme; Le Dur, Annick; Laude, Hubert; Béringue, Vincent

2010-01-01

Prions are unconventional infectious agents thought to be primarily composed of PrPSc, a multimeric misfolded conformer of the ubiquitously expressed host-encoded prion protein (PrPC). They cause fatal neurodegenerative diseases in both animals and humans. The disease phenotype is not uniform within species, and stable, self-propagating variations in PrPSc conformation could encode this ‘strain’ diversity. However, much remains to be learned about the physical relationship between the infectious agent and PrPSc aggregation state, and how this varies according to the strain. We applied a sedimentation velocity technique to a panel of natural, biologically cloned strains obtained by propagation of classical and atypical sheep scrapie and BSE infectious sources in transgenic mice expressing ovine PrP. Detergent-solubilized, infected brain homogenates were used as starting material. Solubilization conditions were optimized to separate PrPSc aggregates from PrPC. The distribution of PrPSc and infectivity in the gradient was determined by immunoblotting and mouse bioassay, respectively. As a general feature, a major proteinase K-resistant PrPSc peak was observed in the middle part of the gradient. This population approximately corresponds to multimers of 12–30 PrP molecules, if constituted of PrP only. For two strains, infectivity peaked in a markedly different region of the gradient. This most infectious component sedimented very slowly, suggesting small size oligomers and/or low density PrPSc aggregates. Extending this study to hamster prions passaged in hamster PrP transgenic mice revealed that the highly infectious, slowly sedimenting particles could be a feature of strains able to induce a rapidly lethal disease. Our findings suggest that prion infectious particles are subjected to marked strain-dependent variations, which in turn could influence the strain biological phenotype, in particular the replication dynamics. PMID:20419156

Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein.

PubMed

Leliveld, S Rutger; Stitz, Lothar; Korth, Carsten

2008-06-10

A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases. Insertional mutations that lead to an increase in the number of octarepeats (ORs) in PrP are linked to familial human prion disease. In this study, we investigated how expansion of the OR domain causes PrP to favor a prion-like conformation. Therefore, we compared the conformational and aggregation modulating properties of wild-type versus expanded OR domains, either as a fusion construct with the protein G B1 domain (GB1-OR) or as an integral part of full-length mouse PrP (MoPrP). Using circular dichroism spectroscopy, we first demonstrated that ORs are not unfolded but exist as an ensemble of three distinct conformers: polyproline helix-like, beta-turn, and "Trp-related". Domain expansion had little effect on the conformation of GB1-OR fusion proteins. When part of MoPrP however, OR domain expansion changed PrP's folding landscape, not by hampering the production of native alpha-helical monomers but by greatly reducing the propensity to form amyloid and by altering the assembly of misfolded, beta-rich aggregates. These features may relate to subtle pH-dependent conformational differences between wild-type and mutant monomers. In conclusion, we propose that PrP insertional mutations are pathogenic because they enhance specific misfolding pathways of PrP rather than by undermining native folding. This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease.

Determinants of tobacco use by students

PubMed Central

Vargas, Lorena Silva; Lucchese, Roselma; da Silva, Andrécia Cósmem; Guimarães, Rafael Alves; Vera, Ivânia; de Castro, Paulo Alexandre

2017-01-01

ABSTRACT OBJECTIVE Estimate the prevalence and determinants of tobacco use by students. METHODS This cross-sectional study, carried out between 2013 and 2014, evaluates 701 public school students between 10 and 79 years of age living in a city in the countryside of the State of Goias, Midwest of Brazil. A structured questionnaire collected the data and the predictor variables were demographic data, family nucleus, religion, physical activity practice, family functionality and parental smoking. Two multivariable models were implemented, the first for occasional tobacco use and the second for regular use, acquiring the measure of prevalence ratio (PR) and their respective 95%CI. Variables with p < 0.10 were included in Poisson regression models with robust variance to obtain the adjusted PR (adPR) and 95%CI. The Wald Chi-Squared test examined the differences between proportions, and values with p < 0.05 were statistically significant. RESULTS The prevalence of occasional and regular tobacco use were 33.4% (95%CI 29.8–36.9) and 6.7% (95%CI 5.0–8.8), respectively. The factors associated with occasional tobacco consumption were age of 15 to 17 years (adPR = 1.98) and above 18 years (adPR = 3.87), male gender (adPR = 1.23), moderate family dysfunction (adPR = 1.30), high family dysfunction (adPR = 1.97) and parental smoking (adPR = 1.60). In regards to regular consumption of tobacco, age above 18 years (adPR = 4.63), lack of religion (adPR = 2.08), high family dysfunction (adPR = 2.35) and parental smoking (adPR = 2.89) remained associated. CONCLUSIONS Students exhibit a high prevalence of occasional and regular tobacco use. This consumption relates to sociodemographic variables and family dysfunction. PMID:28492760

Transitioning to HIV Pre-Exposure Prophylaxis (PrEP) from Non-Occupational Post-Exposure Prophylaxis (nPEP) in a Comprehensive HIV Prevention Clinic: A Prospective Cohort Study.

PubMed

Siemieniuk, Reed A C; Sivachandran, Nirojini; Murphy, Pauline; Sharp, Andrea; Walach, Christine; Placido, Tania; Bogoch, Isaac I

2015-08-01

The uptake of pre-exposure prophylaxis (PrEP) for HIV prevention remains low. We hypothesized that a high proportion of patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP) would be candidates for PrEP based on current CDC guidelines. Outcomes from a comprehensive HIV Prevention Clinic are described. We evaluated all patients who attended the HIV Prevention Clinic for nPEP between January 1, 2013 and September 30, 2014. Each patient was evaluated for PrEP candidacy based on current CDC-guidelines and subjectively based on physician opinion. Patients were then evaluated for initiation of PrEP if they met guideline suggestions. Demographic, social, and behavioral factors were then analyzed with logistic regression for associations with PrEP candidacy and initiation. 99 individuals who attended the nPEP clinic were evaluated for PrEP. The average age was 32 years (range, 18-62), 83 (84%) were male, of whom 46 (55%) men who had have sex with men (MSM). 31 (31%) met CDC guidelines for PrEP initiation, which had very good agreement with physician recommendation (kappa=0.88, 0.78-0.98). Factors associated with PrEP candidacy included sexual exposure to HIV, prior nPEP use, and lack of drug insurance (p<0.05 for all comparisons). Combining nPEP and PrEP services in a dedicated clinic can lead to identification of PrEP candidates and may facilitate PrEP uptake. Strategies to ensure equitable access of PrEP should be explored such that those without drug coverage may also benefit from this effective HIV prevention modality.

Human Parturition Involves Phosphorylation of Progesterone Receptor-A at Serine-345 in Myometrial Cells.

PubMed

Amini, Peyvand; Michniuk, Daniel; Kuo, Kelly; Yi, Lijuan; Skomorovska-Prokvolit, Yelenna; Peters, Gregory A; Tan, Huiqing; Wang, Junye; Malemud, Charles J; Mesiano, Sam

2016-11-01

The hypothesis that phosphorylation of progesterone receptor (PR) isoforms, PR-A and PR-B, in myometrial cells affects progesterone action in the context of human parturition was tested. Immunodetection of phosphoserine (pSer) PR forms in term myometrium revealed that the onset of labor is associated with increased phosphorylation of PR-A at serine-345 (pSer345-PRA) and that pSer345-PRA localized to the nucleus of myometrial cells. In explant cultures of term myometrium generation of pSer345-PRA was induced by interleukin-1β and dependent on progesterone, suggesting that pSer345-PRA generation is induced by a proinflammatory stimulus. In the hTERT-HM A/B human myometrial cell line, abundance of pSer345-PRA was induced by progesterone in a dose- (EC 50 ∼1 nM) and time-dependent manner. Prevention of pSer345 (by site-directed mutagenesis) abolished the capacity for PR-A to inhibit anti-inflammatory actions of progesterone mediated by PR-B but had no effect on the transrepressive activity of PR-A at a canonical progesterone response element. Taken together, the data show that human parturition involves the phosphorylation of PR-A at serine-345 in myometrial cells and that this process is ligand dependent and induced by a proinflammatory stimulus. We also found that in myometrial cells, pSer345 activates the capacity for PR-A to inhibit antiinflammatory actions of progesterone mediated by PR-B. Phosphorylation of PR-A at serine-345 may be an important functional link between tissue-level inflammation and PR-A-mediated functional progesterone withdrawal to trigger parturition.

Human Parturition Involves Phosphorylation of Progesterone Receptor-A at Serine-345 in Myometrial Cells

PubMed Central

Amini, Peyvand; Michniuk, Daniel; Kuo, Kelly; Yi, Lijuan; Skomorovska-Prokvolit, Yelenna; Peters, Gregory A.; Tan, Huiqing; Wang, Junye; Malemud, Charles J.

2016-01-01

The hypothesis that phosphorylation of progesterone receptor (PR) isoforms, PR-A and PR-B, in myometrial cells affects progesterone action in the context of human parturition was tested. Immunodetection of phosphoserine (pSer) PR forms in term myometrium revealed that the onset of labor is associated with increased phosphorylation of PR-A at serine-345 (pSer345-PRA) and that pSer345-PRA localized to the nucleus of myometrial cells. In explant cultures of term myometrium generation of pSer345-PRA was induced by interleukin-1β and dependent on progesterone, suggesting that pSer345-PRA generation is induced by a proinflammatory stimulus. In the hTERT-HMA/B human myometrial cell line, abundance of pSer345-PRA was induced by progesterone in a dose- (EC50 ∼1 nM) and time-dependent manner. Prevention of pSer345 (by site-directed mutagenesis) abolished the capacity for PR-A to inhibit anti-inflammatory actions of progesterone mediated by PR-B but had no effect on the transrepressive activity of PR-A at a canonical progesterone response element. Taken together, the data show that human parturition involves the phosphorylation of PR-A at serine-345 in myometrial cells and that this process is ligand dependent and induced by a proinflammatory stimulus. We also found that in myometrial cells, pSer345 activates the capacity for PR-A to inhibit antiinflammatory actions of progesterone mediated by PR-B. Phosphorylation of PR-A at serine-345 may be an important functional link between tissue-level inflammation and PR-A-mediated functional progesterone withdrawal to trigger parturition. PMID:27653036

Missed Opportunities to Prescribe HIV Pre-Exposure Prophylaxis by Primary Care Providers in Saint Louis, Missouri

PubMed Central

Chan, Philip A.; Harrison, Laura C.; Mayer, Kenneth H.; Nunn, Amy; Mena, Leandro A.; Powderly, William G.

2018-01-01

Abstract Purpose: Optimal HIV pre-exposure prophylaxis (PrEP) scale-up in the United States requires prescribing by primary care providers (PCPs). We assessed barriers to patients obtaining PrEP from their PCPs. Methods: Patients seeking PrEP at an Infectious Diseases (ID) Clinic in St. Louis, Missouri from 2014 to 2016 were asked about demographics, sexual behaviors, whether PrEP was initially sought from their PCP, and barriers to obtaining PrEP from their PCP. Multivariable logistic regression was performed to identify predictors for having asked a PCP for PrEP. Results: Among 102 patients, the median age was 29 years, 58% were white, and 88% were men who have sex with men. Most (65%) had a PCP and, of these, 48% had asked their PCP for PrEP, but were not prescribed it. About half (52%) reported that their PCPs perceived prescribing PrEP as specialty care. Many (39%) indicated that they felt uncomfortable discussing their sexual behaviors with their PCP. Patients with an HIV-positive sex partner in the last 3 months were less likely to ask for PrEP from their PCPs than others (Adjusted Odds Ratio: 0.07; 95% CI: 0.01–0.53). Eighty-three percent of patients were referred to a new PCP with whom they could feel more comfortable discussing PrEP. Conclusions: During initial PrEP implementation, ID specialists can play an important role in providing education and linking PrEP patients to PCPs. However, PCPs may need additional training about PrEP and how to provide culturally sensitive sexual healthcare, if widespread scale-up is to be effective in decreasing HIV incidence. PMID:29688800

Willingness to use HIV pre-exposure prophylaxis among gay men, other men who have sex with men and transgender women in Myanmar.

PubMed

Draper, Bridget L; Fowkes, Freya J I; Oo, Zaw Min; Thein, Zaw Win; Aung, Poe Poe; Veronese, Vanessa; Ryan, Claire; Thant, Myo; Hughes, Chad; Stoové, Mark

2017-07-26

HIV pre-exposure prophylaxis (PrEP) has emerged as a key component of contemporary HIV combination prevention strategies. To explore the local suitability of PrEP, country-specific acceptability studies are needed to inform potential PrEP implementation. In the context of Myanmar, in addition to resource constraints, HIV service access by gay men, other men who have sex with men, and transgender women (GMT) continues to be constrained by legislative and community stigma and marginalization. We aimed to determine PrEP acceptability among GMT in Myanmar and explore the factors associated with willingness to use PrEP. GMT were recruited in Yangon and Mandalay through local HIV prevention outreach programmes in November and December 2014. Quantitative surveys were administered by trained peer educators and collected data on demographics, sexual risk, testing history and PrEP acceptability. A modified six-item PrEP acceptability scale classified self-reported HIV undiagnosed GMT as willing to use PrEP. Multivariable logistic regression identified factors associated with willingness to use PrEP. Among 434 HIV undiagnosed GMT, PrEP awareness was low (5%). PrEP acceptability was high, with 270 (62%) GMT classified as willing to use PrEP. GMT recruited in Mandalay (adjusted odds ratio (aOR) = 1.79; 95%CI = 1.05-3.03), who perceived themselves as likely to become HIV positive (aOR = 1.82; 95%CI = 1.10-3.02), who had more than one recent regular partner (aOR = 2.94; 95%CI = 1.41-6.14), no regular partners (aOR = 2.05; 95%CI = 1.10-3.67), more than five casual partners (aOR = 2.05; 95%CI = 1.06-3.99) or no casual partners (aOR = 2.25; 95%CI = 1.23-4.11) were more likely to be willing to use PrEP. The association between never or only occasionally using condoms with casual partners and willingness to use PrEP was marginally significant (aOR = 2.02; 95%CI = 1.00-4.10). GMT who reported concern about side effects and long-term use of PrEP were less likely (aOR = 0.35; 95%CI = 0.21-0.59) to be willing to use PrEP. This is the first study to assess PrEP acceptability in Myanmar. Findings suggest PrEP is an acceptable prevention option among GMT in Myanmar, providing they are not required to pay for it. Implementation/demonstration projects are needed to explore the feasibility and cost-effectiveness of PrEP as a prevention option for GMT in Myanmar.

Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression.

PubMed

Knutson, Todd P; Daniel, Andrea R; Fan, Danhua; Silverstein, Kevin At; Covington, Kyle R; Fuqua, Suzanne Aw; Lange, Carol A

2012-06-14

Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct phosphorylation. PR-B but not PR-A isoforms are phosphorylated on Ser294 by mitogen activated protein kinase (MAPK) and cyclin dependent kinase 2 (CDK2). Phospho-Ser294 PRs are resistant to ligand-dependent Lys388 SUMOylation (that is, a repressive modification). Antagonism of PR small ubiquitin-like modifier (SUMO)ylation by mitogenic protein kinases suggests a mechanism for derepression (that is, transcriptional activation) of target genes. As a broad range of PR protein expression is observed clinically, a PR gene signature would provide a valuable marker of PR contribution to early breast cancer progression. Global gene expression patterns were measured in T47D and MCF-7 breast cancer cells expressing either wild-type (SUMOylation-capable) or K388R (SUMOylation-deficient) PRs and subjected to pathway analysis. Gene sets were validated by RT-qPCR. Recruitment of coregulators and histone methylation levels were determined by chromatin immunoprecipitation. Changes in cell proliferation and survival were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and western blotting. Finally, human breast tumor cohort datasets were probed to identify PR-associated gene signatures; metagene analysis was employed to define survival rates in patients whose tumors express a PR gene signature. 'SUMO-sensitive' PR target genes primarily include genes required for proliferative and pro-survival signaling. DeSUMOylated K388R receptors are preferentially recruited to enhancer regions of derepressed genes (that is, MSX2, RGS2, MAP1A, and PDK4) with the steroid receptor coactivator, CREB-(cAMP-response element-binding protein)-binding protein (CBP), and mixed lineage leukemia 2 (MLL2), a histone methyltransferase mediator of nucleosome remodeling. PR SUMOylation blocks these events, suggesting that SUMO modification of PR prevents interactions with mediators of early chromatin remodeling at 'closed' enhancer regions. SUMO-deficient (phospho-Ser294) PR gene signatures are significantly associated with human epidermal growth factor 2 (ERBB2)-positive luminal breast tumors and predictive of early metastasis and shortened survival. Treatment with antiprogestin or MEK inhibitor abrogated expression of SUMO-sensitive PR target-genes and inhibited proliferation in BT-474 (estrogen receptor (ER)+/PR+/ERBB2+) breast cancer cells. We conclude that reversible PR SUMOylation/deSUMOylation profoundly alters target gene selection in breast cancer cells. Phosphorylation-induced PR deSUMOylation favors a permissive chromatin environment via recruitment of CBP and MLL2. Patients whose ER+/PR+ tumors are driven by hyperactive (that is, derepressed) phospho-PRs may benefit from endocrine (antiestrogen) therapies that contain an antiprogestin.

Palladium(II) complexes with highly basic imidazolin-2-imines and their reactivity toward small bio-molecules.

PubMed

Bogojeski, Jovana; Volbeda, Jeroen; Freytag, Matthias; Tamm, Matthias; Bugarčić, Živadin D

2015-10-21

A series of novel Pd(ii) complexes with chelating mono(imidazolin-2-imine) and bis(imidazolin-2-imine) ligands were synthesized. The crystal structures of [Pd(DMEAIm(iPr))Cl2] and [Pd(DPENIm(iPr))Cl2] were determined by X-ray diffraction analysis. The reactivity of the six Pd(ii) complexes, namely, [Pd(en)Cl2], [Pd(EAIm(iPr))Cl2], [Pd(DMEAIm(iPr))Cl2], [Pd(DPENIm(iPr))Cl2], [Pd(BL(iPr))Cl2] and [Pd(DACH(Im(iPr))2)Cl2], were investigated. Spectrophotometric acid-base titrations were performed to determine the pKa values of the coordinated water molecules in [Pd(en)(H2O)2](2+), [Pd(EAIm(iPr))(H2O)2](2+), [Pd(DMEAIm(iPr))(H2O)2](2+), [Pd(DPENIm(iPr))(H2O)2](2+), [Pd(BL(iPr))(H2O)2](2+) and [Pd(DACH(Im(iPr))2)(H2O)2](2+). The substitution of the chloride ligands in these complexes by TU, l-Met, l-His and Gly was studied under pseudo-first-order conditions as a function of the nucleophile concentration and temperature using stopped-flow techniques; the sulfur-donor nucleophiles have shown better reactivity than nitrogen-donor nucleophiles. The obtained results indicate that there is a clear correlation between the nature of the imidazolin-2-imine ligands and the acid-base characteristics and reactivity of the resulting Pd(ii) complexes; the order of reactivity of the investigated Pd(ii) complexes is: [Pd(en)Cl2] > [Pd(EAIm(iPr))Cl2] > [Pd(DMEAIm(iPr))Cl2] > [Pd(DPENIm(iPr))Cl2] > [Pd(BL(iPr))Cl2] > [Pd(DACH(Im(iPr))2)Cl2]. The solubility measurements revealed good solubility of the studied imidazolin-2-imine complexes in water, despite the fact that these Pd(ii) complexes are neutral complexes. Based on the performed studies, three unusual features of the novel imidazolin-2-imine Pd(ii) complexes are observed, that is, good solubility in water, very low reactivity and high pKa values. The coordination geometries around the palladium atoms are distorted square-planar; the [Pd(DMEAIm(iPr))Cl2] complex displays Pd-N distances of 2.013(2) and 2.076(2) Å, while the [Pd(DPENIm(iPr))Cl2] complex displays similar Pd-N distances of 2.034(4) and 2.038(3) Å. The studied systems are of interest because little is known about the substitution behavior of imidazolin-2-imine Pd(ii) complexes with bio-molecules under physiological conditions.

Biochemical Characterization of Prions.

PubMed

Fiorini, Michele; Bongianni, Matilde; Monaco, Salvatore; Zanusso, Gianluigi

2017-01-01

Prion disease or transmissible spongiform encephalopathies are characterized by the presence of the abnormal form of the prion protein (PrP Sc ). The pathological and transmissible properties of PrP Sc are enciphered in its secondary and tertiary structures. Since it's well established that different strains of prions are linked to different conformations of PrP Sc , biochemical characterization of prions seems a preliminary but reliable approach to detect, analyze, and compare prion strains. Experimental biochemical procedures might be helpful in distinguishing PrP Sc physicochemical properties and include resistance to proteinase K (PK) digestion, insolubility in nonionic detergents, PK-resistance under denaturing conditions and sedimentation properties in sucrose gradients. This biochemical approach has been extensively applied in human prion disorders and subsequently expanded for PrP Sc characterization in animals. In particular, in sporadic Creutzfedlt-Jakob disease (sCJD) PrP Sc is characterized by two main glycotypes conventionally named Type 1 and Type 2, based on the apparent gel migration at 21 and 19kDa of the PrP Sc PK-resistant fragment. An additional PrP Sc type was identified in sCJD characterized by an unglycosylated dominant glycoform pattern and in 2010 a variably protease-sensitive prionopathy (VPSPr) was reported showing a PrP Sc with an electrophoretic ladder like pattern. Additionally, the presence of PrP Sc truncated fragments completes the electrophoretic characterization of different prion strains. By two-dimensional (2D) electrophoretic analysis additional PrP Sc pattern was identified, since this procedure provides information about the isoelectric point and the different peptides length related to PK cleavage, as well as to glycosylation extent or GPI anchor presence. We here provide and extensive review on PrP Sc biochemical analysis in human and animal prion disorders. Further, we show that PrP Sc glycotypes observed in CJD share similarities with PrP Sc in bovine spongiform encephalopathy forms (BSE). © 2017 Elsevier Inc. All rights reserved.

Protease resistance of infectious prions is suppressed by removal of a single atom in the cellular prion protein.

PubMed

Leske, Henning; Hornemann, Simone; Herrmann, Uli Simon; Zhu, Caihong; Dametto, Paolo; Li, Bei; Laferriere, Florent; Polymenidou, Magdalini; Pelczar, Pawel; Reimann, Regina Rose; Schwarz, Petra; Rushing, Elisabeth Jane; Wüthrich, Kurt; Aguzzi, Adriano

2017-01-01

Resistance to proteolytic digestion has long been considered a defining trait of prions in tissues of organisms suffering from transmissible spongiform encephalopathies. Detection of proteinase K-resistant prion protein (PrPSc) still represents the diagnostic gold standard for prion diseases in humans, sheep and cattle. However, it has become increasingly apparent that the accumulation of PrPSc does not always accompany prion infections: high titers of prion infectivity can be reached also in the absence of protease resistant PrPSc. Here, we describe a structural basis for the phenomenon of protease-sensitive prion infectivity. We studied the effect on proteinase K (PK) resistance of the amino acid substitution Y169F, which removes a single oxygen atom from the β2-α2 loop of the cellular prion protein (PrPC). When infected with RML or the 263K strain of prions, transgenic mice lacking wild-type (wt) PrPC but expressing MoPrP169F generated prion infectivity at levels comparable to wt mice. The newly generated MoPrP169F prions were biologically indistinguishable from those recovered from prion-infected wt mice, and elicited similar pathologies in vivo. Surprisingly, MoPrP169F prions showed greatly reduced PK resistance and density gradient analyses showed a significant reduction in high-density aggregates. Passage of MoPrP169F prions into mice expressing wt MoPrP led to full recovery of protease resistance, indicating that no strain shift had taken place. We conclude that a subtle structural variation in the β2-α2 loop of PrPC affects the sensitivity of PrPSc to protease but does not impact prion replication and infectivity. With these findings a specific structural feature of PrPC can be linked to a physicochemical property of the corresponding PrPSc.

Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.

PubMed

Stenland, Christopher J; Lee, Douglas C; Brown, Paul; Petteway, Stephen R; Rubenstein, Richard

2002-11-01

Therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (TSE) transmission. Previously, hamster-adapted scrapie was used as a model agent to assess TSE clearance in purification steps leading to the isolation of biopharmaceutical proteins. The current study investigated the validity of hamster scrapie as a model for human TSE clearance studies. The partitioning of the pathogenic forms of the prion protein associated with human variant CJD (PrP(vCJD)), human sporadic CJD (PrP(sCJD)) and Gerstmann-Sträussler-Scheinker (PrP(GSS)) syndrome was compared to the partitioning of hamster scrapie (PrP(Sc)) in three plasma protein purification steps. Sheep scrapie (PrP(Sc)) was similarly evaluated. The starting materials for three plasma protein purification steps, cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation, were spiked with brain homogenates containing human PrP(vCJD), human PrP(sCJD), human PrP(GSS), sheep PrP(Sc), and hamster 263K PrP(Sc). The partitioning of the pathogenic form of the PrP was analyzed. Clearance of the pathogenic form of the PrP was measured relative to the effluent fraction. Regardless of the source of the pathogenic prion, clearance was similar to hamster PrP(Sc). A nominal amount of clearance (approx., 1 log), an intermediate amount of clearance (approx., 2 log), and a substantial amount of clearance (> or = 3 log) were observed for the cryoseparation, 3 percent PEG separation, and 11.5 percent PEG separation steps, respectively. In the latter step, no PrP was detected in the effluents. These data demonstrate that human prions, including vCJD prions, can be removed during the purification of human therapeutic proteins and indicate that partitioning of human prions is similar to that observed in the hamster scrapie model.

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection.

PubMed

Di Biagio, Antonio; Riccardi, Niccolò; Signori, Alessio; Maserati, Renato; Nozza, Silvia; Gori, Andrea; Bonora, Stefano; Borderi, Marco; Ripamonti, Diego; Rossi, Maria Cristina; Orofino, Giancarlo; Quirino, Tiziana; Nunnari, Giuseppe; Celesia, Benedetto Maurizio; Martini, Salvatore; Sagnelli, Caterina; Mazzola, Giovanni; Colletti, Pietro; Bartolozzi, Dario; Bini, Teresa; Ladisa, Nicoletta; Castelnuovo, Filippo; Saracino, Annalisa; Lo Caputo, Sergio

2017-01-01

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

Evaluation of critical distances for energy transfer between Pr3+ and Ce3+ in yttrium aluminium garnet

NASA Astrophysics Data System (ADS)

Zeng, Peng; Wei, Xiantao; Zhou, Shaoshuai; Yin, Min; Chen, Yonghu

2016-09-01

A series of Pr3+/Ce3+ doped yttrium aluminium garnet (Y3Al5O12 or simply YAG) phosphors were synthesized to investigate the energy transfer between Pr3+ and Ce3+ for their potential application in a white light-emitting diode and quantum information storage and processing. The excitation and emission spectra of YAG:Pr3+/Ce3+ were measured and analyzed, and it revealed that the reabsorption between Pr3+ and Ce3+ was so weak that it can be ignored, and the energy transfer from Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2) did occur. By analyzing the excitation and the emission spectra, the energy transfer from Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2) was examined in detail with an original strategy deduced from fluorescence dynamics and the Dexter energy transfer theory, and the critical distances of energy transfer were derived to be 7.9 Å and 4.0 Å for Pr3+ (5d) to Ce3+ (5d) and Ce3+ (5d) to Pr3+ (1D2), respectively. The energy transfer rates of the two processes of various concentrations were discussed and evaluated. Furthermore, for the purpose of sensing a single Pr3+ state with a Ce3+ ion, the optimal distance of Ce3+ from Pr3+ was evaluated as 5.60 Å, where the probability of success reaches its maximum value of 78.66%, and meanwhile the probabilities were evaluated for a series of Y3+ sites in a YAG lattice. These results will be of valuable reference for achievement of the optimal energy transfer efficiency in Pr3+/Ce3+ doped YAG and other similar systems.

Pre-exposure prophylaxis of HIV

PubMed Central

Naswa, Smriti; Marfatia, Y. S.

2011-01-01

Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other prevention strategies. Women represent nearly 60% of adults infected with HIV and PrEP can be a female-controlled prevention method for women who are unable to negotiate condom use. Two antiretroviral nucleoside analog HIV-1 reverse transcriptase inhibitor drugs are currently under trial as PrEP drugs, namely tenofovirdisoproxilfumarate (TDF) alone and TDF in combination with emricitabine (FTC), to be taken as daily single dose oral drugs. There are 11 ongoing trials of ARV-based prevention in different at risk populations across the world. The iPrex trial showed that daily use of oral TDF/FTC by MSM resulted in 44% reduction in the incidence of HIV. This led to publication of interim guidance by CDC to use of PrEP by health providers for MSM. Few other trials are Bangkok Tenofovir Study, Partners PrEP Study, FEM-PrEP study, and VOICE (MTN-003) study. Future trials are being formulated for intermittent PrEP (iPrEP) where drugs are taken before and after sex, “stand-in dose” iPrEP, vaginal or rectal PrEP, etc. There are various issues/concerns with PrEP such as ADRs and resistance to TDF/FTC, adherence to drugs, acceptability, sexual disinhibition, use of PrEP as first line of defense for HIV without other prevention strategies, and cost. The PrEP has a potential to address unmet need in public health if delivered as a part of comprehensive toolkit of prevention services, including risk-reduction, correct and consistent use of condoms, and diagnosis and treatment of sexually transmitted infections. PMID:21799568

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

PubMed

Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits observed in clinical trials are maintained in real-world use.

Methamphetamine increases Prion Protein and induces dopamine-dependent expression of protease resistant PrPsc.

PubMed

Ferrucci, M; Ryskalin, L; Biagioni, F; Gambardella, S; Busceti, C L; Falleni, A; Lazzeri, G; Fornai, F

2017-07-01

The cellular prion protein (PrPc) is physiologically expressed within selective brain areas of mammals. Alterations in the secondary structure of this protein lead to scrapie-like prion protein (PrPsc), which precipitates in the cell. PrPsc has been detected in infectious, inherited or sporadic neurodegenerative disorders. Prion protein metabolism is dependent on autophagy and ubiquitin proteasome. Despite not being fully elucidated, the physiological role of prion protein relates to chaperones which rescue cells under stressful conditions.Methamphetamine (METH) is a widely abused drug which produces oxidative stress in various brain areas causing mitochondrial alterations and protein misfolding. These effects produce a compensatory increase of chaperones while clogging cell clearing pathways. In the present study, we explored whether METH administration modifies the amount of PrPc. Since high levels of PrPc when the clearing systems are clogged may lead to its misfolding into PrPsc, we further tested whether METH exposure triggers the appearance of PrPsc. We analysed the effects of METH and dopamine administration in PC12 and striatal cells by using SDS-PAGE Coomassie blue, immune- histochemistry and immune-gold electron microscopy. To analyze whether METH administration produces PrPsc aggregates we used antibodies directed against PrP following exposure to proteinase K or sarkosyl which digest folded PrPc but misfolded PrPsc. We fond that METH triggers PrPsc aggregates in DA-containing cells while METH is not effective in primary striatal neurons which do not produce DA. In the latter cells exogenous DA is needed to trigger PrPsc accumulation similarly to what happens in DA containing cells under the effects of METH. The present findings, while fostering novel molecular mechanisms involving prion proteins, indicate that, cell pathology similar to prion disorders can be mimicked via a DA-dependent mechanism by a drug of abuse.

Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

PubMed

Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

2018-06-01

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

The Role of Shed PrPc in the Neuropathogenesis of HIV Infection.

PubMed

Megra, Bezawit W; Eugenin, Eliseo A; Berman, Joan W

2017-07-01

HIV-1 enters the CNS soon after peripheral infection and causes chronic neuroinflammation and neuronal damage that leads to cognitive impairment in 40-70% of HIV-infected people. The nonpathogenic cellular isoform of the human prion protein (PrP c ) is an adhesion molecule constitutively expressed in the CNS. Previously, our laboratory showed that shed PrP c (sPrP c ) is increased in the cerebrospinal fluid of HIV-infected people with cognitive deficits as compared with infected people with no impairment. In this article, we demonstrate that CCL2 and TNF-α, inflammatory mediators that are elevated in the CNS of HIV-infected people, increase shedding of PrP c from human astrocytes by increasing the active form of the metalloprotease ADAM10. We show that the consequence of this shedding can be the production of inflammatory mediators, because treatment of astrocytes with rPrP c increased secretion of CCL2, CXCL-12, and IL-8. Supernatants from rPrP c -treated astrocytes containing factors produced in response to this treatment, but not rPrP c by itself, cause increased chemotaxis of both uninfected and HIV-infected human monocytes, suggesting a role for sPrP c in monocyte recruitment into the brain. Furthermore, we examined whether PrP c participates in glutamate uptake and found that rPrP c decreased uptake of this metabolite in astrocytes, which could lead to neurotoxicity and neuronal loss. Collectively, our data characterize mediators involved in PrP c shedding and the effect of this sPrP c on monocyte chemotaxis and glutamate uptake from astrocytes. We propose that shedding of PrP c could be a potential target for therapeutics to limit the cognitive impairment characteristic of neuroAIDS. Copyright © 2017 by The American Association of Immunologists, Inc.

Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER/PR target genes.

PubMed

Diep, Caroline H; Ahrendt, Hannah; Lange, Carol A

2016-10-01

Progesterone Receptors (PRs) are critical effectors of estrogen receptor (ER) signaling required for mammary gland development and reproductive proficiency. In breast and reproductive tract malignancies, PR expression is a clinical prognostic marker of ER action. While estrogens primarily regulate PR expression, other factors likely contribute to a dynamic range of receptor expression across diverse tissues. In this study, we identified estrogen-independent but progestin (R5020)-dependent regulation of ER target genes including PGR in ER+/PR+ cancer cell lines. R5020 (10nM-10μM range) induced dose-dependent PR mRNA and protein expression in the absence of estrogen but required both PR and ERα. Antagonists of either PR (RU486, onapristone) or ERα (ICI 182,780) attenuated R5020 induction of TFF1, CTSD, and PGR. Chromatin immunoprecipitation (ChIP) assays performed on ER+/PR+ cells demonstrated that both ERα and PR were recruited to the same ERE/Sp1 site-containing region of the PGR proximal promoter in response to high dose progestin (10μM). Recruitment of ERα and PR to chromatin and subsequent PR mRNA induction were dependent upon rapid activation of MAPK/ERK and AKT; inhibition of these kinase pathways via U0126 or LY294002 blocked these events. Overall, we have identified a novel mechanism of ERα activation initiated by rapid PR-dependent kinase pathway activation and associated with phosphorylation of ERα Ser118 for estrogen-independent but progestin-dependent ER/PR cross talk. These studies may provide insight into mechanisms of persistent ER-target gene expression during periods of hormone (i.e. estrogen) ablation and suggest caution following prolonged treatment with aromatase or CYP17 inhibitors (i.e. contexts when progesterone levels may be abnormally elevated). Copyright © 2016 Elsevier Inc. All rights reserved.

Validation of TRMM Precipitation Radar Through Comparison of its Multi-Year Measurements to Ground-Based Radar

NASA Technical Reports Server (NTRS)

Liao, Liang; Meneghini, Robert

2010-01-01

A procedure to accurately resample spaceborne and ground-based radar data is described, and then applied to the measurements taken from the Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) and the ground-based Weather Surveillance Radar-1988 Doppler (WSR-88D or WSR) for the validation of the PR measurements and estimates. Through comparisons with the well-calibrated, non-attenuated WSR at Melbourne, Florida for the period 1998-2007, the calibration of the Precipitation Radar (PR) aboard the TRMM satellite is checked using measurements near the storm top. Analysis of the results indicates that the PR, after taking into account differences in radar reflectivity factors between the PR and WSR, has a small positive bias of 0.8 dB relative to the WSR, implying a soundness of the PR calibration in view of the uncertainties involved in the comparisons. Comparisons between the PR and WSR reflectivities are also made near the surface for evaluation of the attenuation-correction procedures used in the PR algorithms. It is found that the PR attenuation is accurately corrected in stratiform rain but is underestimated in convective rain, particularly in heavy rain. Tests of the PR estimates of rainfall rate are conducted through comparisons in the overlap area between the TRMM overpass and WSR scan. Analyses of the data are made both on a conditional basis, in which the instantaneous rain rates are compared only at those pixels where both the PR and WSR detect rain, and an unconditional basis, in which the area-averaged rain rates are estimated independently for the PR and WSR. Results of the conditional rain comparisons show that the PR-derived rain is about 9% greater and 19% less than the WSR estimates for stratiform and convective storms, respectively. Overall, the PR tends to underestimate the conditional mean rain rate by 8% for all rain categories, a finding that conforms to the results of the area-averaged rain (unconditional) comparisons.

Humidity assay for studying plant-pathogen interactions in miniature controlled discrete humidity environments with good throughput

PubMed Central

Jiang, Huawei; Sahu, Binod Bihari; Kambakam, Sekhar; Singh, Prashant; Wang, Xinran; Wang, Qiugu; Bhattacharyya, Madan K.; Dong, Liang

2016-01-01

This paper reports a highly economical and accessible approach to generate different discrete relative humidity conditions in spatially separated wells of a modified multi-well plate for humidity assay of plant-pathogen interactions with good throughput. We demonstrated that a discrete humidity gradient could be formed within a few minutes and maintained over a period of a few days inside the device. The device consisted of a freeway channel in the top layer, multiple compartmented wells in the bottom layer, a water source, and a drying agent source. The combinational effects of evaporation, diffusion, and convection were synergized to establish the stable discrete humidity gradient. The device was employed to study visible and molecular disease phenotypes of soybean in responses to infection by Phytophthora sojae, an oomycete pathogen, under a set of humidity conditions, with two near-isogenic soybean lines, Williams and Williams 82, that differ for a Phytophthora resistance gene (Rps1-k). Our result showed that at 63% relative humidity, the transcript level of the defense gene GmPR1 was at minimum in the susceptible soybean line Williams and at maximal level in the resistant line Williams 82 following P. sojae CC5C infection. In addition, we investigated the effects of environmental temperature, dimensional and geometrical parameters, and other configurational factors on the ability of the device to generate miniature humidity environments. This work represents an exploratory effort to economically and efficiently manipulate humidity environments in a space-limited device and shows a great potential to facilitate humidity assay of plant seed germination and development, pathogen growth, and plant-pathogen interactions. Since the proposed device can be easily made, modified, and operated, it is believed that this present humidity manipulation technology will benefit many laboratories in the area of seed science, plant pathology, and plant-microbe biology, where humidity is an important factor that influences plant disease infection, establishment, and development. PMID:27279932

PrEP awareness and perceived barriers among single young men who have sex with men.

PubMed

Bauermeister, Jose A; Meanley, Steven; Pingel, Emily; Soler, Jorge H; Harper, Gary W

2013-10-01

Pre-exposure prophylaxis (PrEP) has the potential to help reduce new HIV infections among young men who have sex with men (YMSM). Using a cross-sectional survey of YMSM (N=1,507; ages 18-24), we gauged YMSM's PrEP awareness and PrEP-related beliefs regarding side effects, accessibility, and affordability. Overall, 27% of the sample had heard about PrEP; 1% reported ever using PrEP prior to sex. In a multivariate logistic regression, we found that YMSM were more likely to have heard about PrEP if they were older, more educated, were residentially unstable in the prior 30 days, had insurance, or reported having at least one sexually transmitted infection in their lifetime. We found no differences by race/ethnicity, history of incarceration, or recent sexual risk behavior. In multivariate linear regression models, Black and Latino YMSM were more likely than Whites to state they would not use PrEP because of side effect concerns. YMSM were more likely to indicate that they would not be able to afford PrEP if they did not have insurance or if they had a prior sexually transmitted infection, PrEP rollout may be hindered due to lack of awareness, as well as perceived barriers regarding its use. We propose strategies to maximize equity in PrEP awareness and access if it is to be scaled up among YMSM.

Infectious prions and proteinopathies.

PubMed

Barron, Rona M

2017-01-02

Transmissible spongiform encephalopathies (TSEs) are caused by an infectious agent that is thought to consist of only misfolded and aggregated prion protein (PrP). Unlike conventional micro-organisms, the agent spreads and propagates by binding to and converting normal host PrP into the abnormal conformer, increasing the infectious titre. Synthetic prions, composed of refolded fibrillar forms of recombinant PrP (rec-PrP) have been generated to address whether PrP aggregates alone are indeed infectious prions. In several reports, the development of TSE disease has been described following inoculation and passage of rec-PrP fibrils in transgenic mice and hamsters. However in studies described here we show that inoculation of rec-PrP fibrils does not always cause clinical TSE disease or increased infectious titre, but can seed the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL). These data are reminiscent of the "prion-like" spread of misfolded protein in other models of neurodegenerative disease following inoculation of transgenic mice with pre-formed amyloid seeds. Protein misfolding, even when the protein is PrP, does not inevitably lead to the development of an infectious TSE disease. It is possible that most in vivo and in vitro produced misfolded PrP is not infectious and that only a specific subpopulation is associated with infectivity and neurotoxicity.

The Novel Gene VpPR4-1 from Vitis pseudoreticulata Increases Powdery Mildew Resistance in Transgenic Vitis vinifera L.

PubMed Central

Dai, Lingmin; Wang, Dan; Xie, Xiaoqing; Zhang, Chaohong; Wang, Xiping; Xu, Yan; Wang, Yuejin; Zhang, Jianxia

2016-01-01

Pathogenesis-related proteins (PRs) can lead to increased resistance of the whole plant to pathogen attack. Here, we isolate and characterize a PR-4 protein (VpPR4-1) from a wild Chinese grape Vitis pseudoreticulata which shows greatly elevated transcription following powdery mildew infection. Its expression profiles under a number of abiotic stresses were also investigated. Powdery mildew, salicylic acid, and jasmonic acid methyl ester significantly increased the VpPR4-1 induction while NaCl and heat treatments just slightly induced VpPR4-1 expression. Abscisic acid and cold treatment slightly affected the expression level of VpPR4-1. The VpPR4-1 gene was overexpressed in 30 regenerated V. vinifera cv. Red Globe via Agrobacterium tumefaciens-mediated transformation and verified by the Western blot. The 26 transgenic grapevines exhibited higher expression levels of PR-4 protein content than wild-type vines and six of them were inoculated with powdery mildew which showed that the growth of powdery mildew was repressed. The powdery mildew-resistance of Red Globe transformed with VpPR4-1 was enhanced inoculated with powdery mildew. Moreover, other powdery mildew resistant genes were associated with feedback regulation since VpPR4-1 is in abundance. This study demonstrates that PR-4 protein in grapes plays a vital role in defense against powdery mildew invasion. PMID:27303413

The Novel Gene VpPR4-1 from Vitis pseudoreticulata Increases Powdery Mildew Resistance in Transgenic Vitis vinifera L.

PubMed

Dai, Lingmin; Wang, Dan; Xie, Xiaoqing; Zhang, Chaohong; Wang, Xiping; Xu, Yan; Wang, Yuejin; Zhang, Jianxia

2016-01-01

Pathogenesis-related proteins (PRs) can lead to increased resistance of the whole plant to pathogen attack. Here, we isolate and characterize a PR-4 protein (VpPR4-1) from a wild Chinese grape Vitis pseudoreticulata which shows greatly elevated transcription following powdery mildew infection. Its expression profiles under a number of abiotic stresses were also investigated. Powdery mildew, salicylic acid, and jasmonic acid methyl ester significantly increased the VpPR4-1 induction while NaCl and heat treatments just slightly induced VpPR4-1 expression. Abscisic acid and cold treatment slightly affected the expression level of VpPR4-1. The VpPR4-1 gene was overexpressed in 30 regenerated V. vinifera cv. Red Globe via Agrobacterium tumefaciens-mediated transformation and verified by the Western blot. The 26 transgenic grapevines exhibited higher expression levels of PR-4 protein content than wild-type vines and six of them were inoculated with powdery mildew which showed that the growth of powdery mildew was repressed. The powdery mildew-resistance of Red Globe transformed with VpPR4-1 was enhanced inoculated with powdery mildew. Moreover, other powdery mildew resistant genes were associated with feedback regulation since VpPR4-1 is in abundance. This study demonstrates that PR-4 protein in grapes plays a vital role in defense against powdery mildew invasion.

PrPC Undergoes Basal to Apical Transcytosis in Polarized Epithelial MDCK Cells

PubMed Central

Arkhipenko, Alexander; Syan, Sylvie; Victoria, Guiliana Soraya

2016-01-01

The Prion Protein (PrP) is an ubiquitously expressed glycosylated membrane protein attached to the external leaflet of the plasma membrane via a glycosylphosphatidylinositol anchor (GPI). While the misfolded PrPSc scrapie isoform is the infectious agent of prion disease, the cellular isoform (PrPC) is an enigmatic protein with unclear function. Of interest, PrP localization in polarized MDCK cells is controversial and its mechanism of trafficking is not clear. Here we investigated PrP traffic in MDCK cells polarized on filters and in three-dimensional MDCK cysts, a more physiological model of polarized epithelia. We found that, unlike other GPI-anchored proteins (GPI-APs), PrP undergoes basolateral-to-apical transcytosis in fully polarized MDCK cells. Following this event full-length PrP and its cleavage fragments are segregated in different domains of the plasma membrane in polarized cells in both 2D and 3D cultures. PMID:27389581

The multivesicular body is the major internal site of prion conversion

PubMed Central

Yim, Yang-In; Park, Bum-Chan; Yadavalli, Rajgopal; Zhao, Xiaohong; Eisenberg, Evan; Greene, Lois E.

2015-01-01

ABSTRACT The conversion of the properly folded prion protein, PrPc, to its misfolded amyloid form, PrPsc, occurs as the two proteins traffic along the endocytic pathway and PrPc is exposed to PrPsc. To determine the specific site of prion conversion, we knocked down various proteins in the endocytic pathway including Rab7a, Tsg101 and Hrs (also known as HGS). PrPsc was markedly reduced in two chronically infected cell lines by preventing the maturation of the multivesicular body, a process that begins in the early endosome and ends with the sorting of cargo to the lysosome. By contrast, knocking down proteins in the retromer complex, which diverts cargo away from the multivesicular body caused an increase in PrPsc levels. These results suggest that the multivesicular body is the major site for intracellular conversion of PrPc to PrPsc. PMID:25663703

Radioimmunotherapy of MCF7 breast cancer cell line with 131I-PR81 monoclonal antibody against MUC1: comparison of direct and indirect radioiodination methods.

PubMed

Mohammadnejad, Javad; Rasaee, Mohammad Javad; Babaei, Mohammad Hosein; Paknejad, Malihe; Hasan, Zahir Mohammad; Salouti, Mojtaba; Gandomkar, Mostafa; Sadri, Keyvan

2010-01-01

PR81 is a monoclonal antibody that binds with high affinity to MUC1, which is over expressed on breast and other tumors. The objective of this study was to compare the two labeling methods (direct and indirect radioiodination) for application of this antibody against MUC1 as a radioimmunotherapeutical agent.Monoclonal antibody (PR81) against the tandem repeat of the core protein (MUC1) was prepared, characterized, purified, and labeled with 131I using the direct (chloramin-T) and indirect (Fmoc-D-Tyr (tBu)-D-Tyr (tBu)-D-Lys (Boc)-OH (YYK) attached to N-hydroxysuccinimide as a linker between PR81 and 131I) methods. The immunoreactivity of 131I-PR81 and 131I-TP-PR81 complexes with MUC1 (the native protein), BSA-P20 (a 20 amino acid corresponding the tandem repeat of MUC1) and MCF7 cell line were performed by RIA. In vitro stability of 131I-PR81 and 131I-YYK-peptide-PR81 complexes in human serum was determined by thin layer chromatography (TLC). Cell toxicity and in vitro internalization studies were performed with the MCF7 cell line, and the tissue biodistribution of the 131I-PR81 and 131I- YYK-peptide -PR81 complexes was evaluated in normal BALB/c mice at 4, 24 and 48 hrs. The labeling efficiency was determined by measuring the percentage recovery of radioactivity in the final product relative to the initial activity in the shipment vial, was found to be 59.9% +/- 7.9% for direct and 50% +/- 3.2% for indirect methods. 131I-PR81 and 131I- YYK- peptide -PR81 complexes showed high immunoreactivity towards MUC1 protein, BSA-P20 and MCF7 cell line. In vitro stability of the labeled products in human serum which was measured by thin layer chromatography (TLC) was found to be more than 50% over 24 hr for 131I-PR81 and 70% for 131I- YYK-peptide -PR81 complexes. Cell toxicity and in vitro internalization studies showed that the 131I-PR81 and 131I- YYK-peptide -PR81 complexes inhibited 80% growth of the MCF7 cultured cell lines in vitro in a high concentration and up to 40% of the 131I-PR81 and 60% of the 131I- YYK-peptide -PR81 complexes internalized after 24 h. Biodistribution studies were performed in normal BALB/c mice at 4, 24 and 48 hrs post-injection. Thyroid and stomach levels from PR81 labeled with 131I- YYK-peptide were two- to three- fold less than those with directly labeled 131I-PR81, suggesting low recognition of its D-iodotyrosine residue by endogenous deiodinase. These results show that the indirect labeling was better than the indirect labeling and 131I- YYK-peptide -PR81 may be considered as a promising candidate for therapy of breast cancer.

Recombinant PrPSc shares structural features with brain-derived PrPSc suggesting that they have a similar architecture: Insights from limited proteolysis

USDA-ARS?s Scientific Manuscript database

An extensive body of experimental and spectroscopic evidence supports the hypothesis that PrPSc is a multimer of 4-rung ß-solenoids, and that individual PrPSc solenoids stack to form amyloid fibers. We recently used limited proteolysis to map the ß-strands and connecting loops that make up the PrPSc...

75 FR 51531 - Proposed Collection; Comment Request for Forms 941, 941-PR, 941-SS, 941-X, 941-X(PR), Schedule B...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

... 941, 941-PR, 941- SS, 941-X, 941-X(PR), Schedule B (Form 941), Schedule R (Form 941) and Schedule B... Islands, and the U.S. Virgin Islands), 941-X, Adjusted Employer's Quarterly Federal Tax Return or Claim for Refund, 941-X(PR), Ajuste a la Declaracion Federal Trimestral del Patrono o Reclamacion de...

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa

PubMed Central

Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R.; Bukusi, Elizabeth A.; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E.; Ware, Norma C.; Wyatt, Monique A.; Marzinke, Mark A.; Frenkel, Lisa M.; Celum, Connie; Baeten, Jared M.

2017-01-01

Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods: We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results: We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.   Conclusions: PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation. PMID:29355231

Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV: uptake, use, and effectiveness in an open-label demonstration project in East Africa.

PubMed

Heffron, Renee; Ngure, Kenneth; Odoyo, Josephine; Bulya, Nulu; Tindimwebwa, Edna; Hong, Ting; Kidoguchi, Lara; Donnell, Deborah; Mugo, Nelly R; Bukusi, Elizabeth A; Katabira, Elly; Asiimwe, Stephen; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Haberer, Jessica E; Ware, Norma C; Wyatt, Monique A; Marzinke, Mark A; Frenkel, Lisa M; Celum, Connie; Baeten, Jared M

2017-11-06

Introduction : Pre-exposure prophylaxis (PrEP) can provide high protection against HIV infection and is a recommended intervention for HIV-negative persons with substantial HIV risk, such as individuals with a partner living with HIV.  Demonstration projects of PrEP have been conducted in diverse settings worldwide to illustrate practical examples of how PrEP can be delivered.  Methods : We evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV serodiscordant couples in an open-label demonstration project in East Africa.  The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP for HIV-negative partners within serodiscordant couples prior to and during the first 6 months after the partner living with HIV initiated antiretroviral therapy (ART).  We measured adherence to PrEP through medication event monitoring system (MEMS) bottle caps and quantification of tenofovir in plasma among a random sample of participants. We estimated HIV infections prevented using a counterfactual cohort simulated from the placebo arm of a previous PrEP clinical trial. Results : We enrolled 1,010 HIV serodiscordant couples that were naïve to ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71% of HIV-negative participants took ≥80% of expected doses, as recorded via MEMS, and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV infections were observed (incidence rate=0.24 per 100 person-years), a 95% reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV incidence for the population in the absence of PrEP integrated into HIV treatment services.   Conclusions : PrEP uptake and adherence were high and incident HIV was rare in this PrEP demonstration project for African HIV-negative individuals whose partners were known to be living with HIV.  Delivery of PrEP to HIV-negative partners within HIV serodiscordant couples was feasible and should be prioritized for wide-scale implementation.

Who Will Use Pre-Exposure Prophylaxis (PrEP) and Why?: Understanding PrEP Awareness and Acceptability amongst Men Who Have Sex with Men in the UK--A Mixed Methods Study.

PubMed

Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa

2016-01-01

Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18-25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities.

Who Will Use Pre-Exposure Prophylaxis (PrEP) and Why?: Understanding PrEP Awareness and Acceptability amongst Men Who Have Sex with Men in the UK – A Mixed Methods Study

PubMed Central

Frankis, Jamie; Young, Ingrid; Flowers, Paul; McDaid, Lisa

2016-01-01

Background Recent clinical trials suggest that pre-exposure prophylaxis (PrEP) may reduce HIV transmission by up to 86% for men who have sex with men (MSM), whilst relatively high levels of PrEP acceptability have been reported to date. This study examines PrEP awareness amongst sub-groups of MSM communities and acceptability amongst MSM in a low prevalence region (Scotland, UK), using a mixed methods design. Methods Quantitative surveys of n = 690 MSM recruited online via social and sociosexual media were analysed using descriptive statistics and multivariate logistic regression. In addition, n = 10 in-depth qualitative interviews with MSM were analysed thematically. Results Under one third (29.7%) of MSM had heard of PrEP, with awareness related to living in large cities, degree level education, commercial gay scene use and reporting an HIV test in the last year. Just under half of participants (47.8%) were likely to use PrEP if it were available but there was no relationship between PrEP acceptability and previous PrEP awareness. Younger men (18–25 years) and those who report higher risk UAI were significantly more likely to say they would use PrEP. Qualitative data described specific PrEP scenarios, illustrating how risk, patterns of sexual practice and social relationships could affect motivation for and nature of PrEP use. Conclusion These findings suggest substantial interest PrEP amongst MSM reporting HIV risk behaviours in Scotland. Given the Proud results, there is a strong case to investigate PrEP implementation within the UK. However, it appears that disparities in awareness have already emerged along traditional indicators of inequality. Our research identifies the need for comprehensive support when PrEP is introduced, including a key online component, to ensure equity of awareness across diverse MSM communities (e.g. by geography, education, gay scene use and HIV proximity), as well as to responding to the diverse informational and sexual health needs of all MSM communities. PMID:27093430

Tris(phosphinoamide)-supported uranium-cobalt heterobimetallic complexes featuring Co → U dative interactions.

PubMed

Napoline, J Wesley; Kraft, Steven J; Matson, Ellen M; Fanwick, Phillip E; Bart, Suzanne C; Thomas, Christine M

2013-10-21

A series of tris- and tetrakis(phosphinoamide) U/Co complexes has been synthesized. The uranium precursors, (η(2)-Ph2PN(i)Pr)4U (1), (η(2)-(i)Pr2PNMes)4U (2), (η(2)-Ph2PN(i)Pr)3UCl (3), and (η(2)-(i)Pr2PNMes)3UI (4), were easily accessed via addition of the appropriate stoichiometric equivalents of [Ph2PN(i)Pr]K or [(i)Pr2PNMes]K to UCl4 or UI4(dioxane)2. Although the phosphinoamide ligands in 1 and 4 have been shown to coordinate to U in an η(2)-fashion in the solid state, the phosphines are sufficiently labile in solution to coordinate cobalt upon addition of CoI2, generating the heterobimetallic Co/U complexes ICo(Ph2PN(i)Pr)3U[η(2)-Ph2PN(i)Pr] (5), ICo((i)Pr2PNMes)3U[η(2)-((i)Pr2PNMes)] (6), ICo(Ph2PN(i)Pr)3UI (7), and ICo((i)Pr2PNMes)3UI (8). Structural characterization of complexes 5 and 7 reveals reasonably short Co-U interatomic distances, with 7 exhibiting the shortest transition metal-uranium distance ever reported (2.874(3) Å). Complexes 7 and 8 were studied by cyclic voltammetry to examine the influence of the metal-metal interaction on the redox properties compared with both monometallic Co and heterobimetallic Co/Zr complexes. Theoretical studies are used to further elucidate the nature of the transition metal-actinide interaction.

Characterization of PrNiO3-δ as oxygen electrode for SOFCs

NASA Astrophysics Data System (ADS)

Vibhu, Vaibhav; Flura, Aurélien; Nicollet, Clément; Fourcade, Sébastien; Penin, Nicolas; Bassat, Jean-Marc; Grenier, Jean-Claude; Rougier, Aline; Pouchard, Michel

2018-07-01

The praseodymium nickelate PrNiO3-δ was recently identified as one of the decomposition products of Pr2NiO4+δ oxygen electrode, raising the question of the role of this perovskite compound on the Pr2NiO4+δ performance and ageing behaviour. Herein, the electrochemical properties of PrNiO3-δ as cathode for Solid Oxide Fuel Cells (SOFCs) is reported. PrNiO3-δ, synthesized from the citrate-nitrate route, cristallizes in an orthorhombic structure (S.G.: Pnma). Under air, a transition to high temperature rhombohedral structure (S.G.: R-3c) occurs at around 600 °C, while its oxygen vacancy amount increases from δ ≈ 0.05 at room temperature up to 0.10 at high temperature. Thermal gravimetry analysis (TGA) measurements coupled with X-ray diffraction (XRD) characterizations show that above 1000 °C, in air, PrNiO3-δ starts to decompose into Pr2NiO4+δ and NiO through an intermediate transformation into Pr4Ni3O10+δ. The value of the polarization resistance (Rp) of co-sintered GDC-PrNiO3-δ electrode, at 950 °C in air for 2 h, is 0.91 Ω cm2 at 600 °C under air. It remains much higher than that of co-sintered GDC-Pr2NiO4+δ electrode (Rp = 0.15 Ω cm2), which means that the perovskite does not play any significant role in the electrochemical performance during long term operation of the Pr2NiO4+δ electrode.

Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer

PubMed Central

Singhal, Hari; Greene, Marianne E.; Tarulli, Gerard; Zarnke, Allison L.; Bourgo, Ryan J.; Laine, Muriel; Chang, Ya-Fang; Ma, Shihong; Dembo, Anna G.; Raj, Ganesh V.; Hickey, Theresa E.; Tilley, Wayne D.; Greene, Geoffrey L.

2016-01-01

The functional role of progesterone receptor (PR) and its impact on estrogen signaling in breast cancer remain controversial. In primary ER+ (estrogen receptor–positive)/PR+ human tumors, we report that PR reprograms estrogen signaling as a genomic agonist and a phenotypic antagonist. In isolation, estrogen and progestin act as genomic agonists by regulating the expression of common target genes in similar directions, but at different levels. Similarly, in isolation, progestin is also a weak phenotypic agonist of estrogen action. However, in the presence of both hormones, progestin behaves as a phenotypic estrogen antagonist. PR remodels nucleosomes to noncompetitively redirect ER genomic binding to distal enhancers enriched for BRCA1 binding motifs and sites that link PR and ER/PR complexes. When both hormones are present, progestin modulates estrogen action, such that responsive transcriptomes, cellular processes, and ER/PR recruitment to genomic sites correlate with those observed with PR alone, but not ER alone. Despite this overall correlation, the transcriptome patterns modulated by dual treatment are sufficiently different from individual treatments, such that antagonism of oncogenic processes is both predicted and observed. Combination therapies using the selective PR modulator/antagonist (SPRM) CDB4124 in combination with tamoxifen elicited 70% cytotoxic tumor regression of T47D tumor xenografts, whereas individual therapies inhibited tumor growth without net regression. Our findings demonstrate that PR redirects ER chromatin binding to antagonize estrogen signaling and that SPRMs can potentiate responses to antiestrogens, suggesting that cotargeting of ER and PR in ER+/PR+ breast cancers should be explored. PMID:27386569

Factors influencing uptake of pre-exposure prophylaxis: some qualitative insights from an intervention study of men who have sex with men in China.

PubMed

Liu, Chunxing; Ding, Yingying; Ning, Zhen; Gao, Meiyang; Liu, Xing; Wong, Frank Y; He, Na

2018-02-01

Pre-exposure prophylaxis (PrEP) is a biomedical approach for preventing the acquisition of HIV in populations at substantial risk for HIV. However, its uptake among men who have sex with men (MSM) is low in China. The study aimed to identify factors that might influence MSM's uptake and use of PrEP. In-depth interviews were conducted with 32 self-identified MSM from a PrEP intervention study evaluating daily oral tenofovir disoproxil fumarate (TDF) to prevent HIV infection. Of these men, 11 were presently using the 'TDF' group; 8 from the 'change-over' group (i.e. initially used PrEP but subsequently quitted); and 13 from the non-user group. Data were analysed using thematic approach. Perception of low HIV risk, mistrust of the national PrEP program, and concerns of side effects were the main reasons for not wanting to use PrEP. Also, lack of main sexual partner's support, difficulties in adhering to the daily TDF regimen, and the inconvenient schedules in securing the medicine were the major reasons for not wanting to use or quitting the use of PrEP. On the other hand, perceived high HIV risk, beliefs in efficacy of PrEP, and worries of transmitting HIV to families were the major motives for PrEP uptake. Findings suggest that PrEP implementation strategies should first address issues including but not limited to accurate self-assessment of HIV risk, mistrust and limited knowledge about medical trials and PrEP, and ease of accessing PrEP.

Knowledge, attitudes, and beliefs about HIV pre-exposure prophylaxis among US Air Force Health Care Providers

PubMed Central

Hakre, Shilpa; Blaylock, Jason M; Dawson, Peter; Beckett, Charmagne; Garges, Eric C; Michael, Nelson L; Danaher, Patrick J; Scott, Paul T; Okulicz, Jason F

2016-01-01

Abstract Providers are central to effective implementation of HIV pre-exposure prophylaxis (PrEP). Primary care providers (PCP) and infectious disease physicians (ID) in the US Air Force (USAF) participated in a cross-sectional survey regarding knowledge, attitudes, and beliefs toward HIV PrEP. Characteristics associated with PrEP knowledge were assessed in univariate and multivariate analyses. Among 403 (40% of 1015 providers) participants, 9% (PCP 383, ID 20) ever prescribed PrEP. In univariate analysis, years in practice, number of HIV-infected patients treated in the past 12 months, past prescription of antiretrovirals for HIV prevention, frequency of prescribing PrEP in the past 12 months, and ever being questioned by a patient about PrEP were associated with PrEP knowledge (P < 0.05). In multivariate analysis, providers who had ever prescribed antiretrovirals to prevent HIV (AOR: 2.37, 95% CI: 1.27–4.42) had greater odds of high PrEP knowledge. Despite concerns about medication side effects (overall 67%: PCP 68%, ID 85%) and prescribing PrEP without clear evidence (overall 60%: PCP 65%, ID 62%), 64% (PCP 65%, ID 85%) of participants indicated PrEP should be offered in the Military Health System and 68% (PCP 70%, ID 100%) disagreed with the statement that their patient population was not at risk for HIV infection. Successful PrEP implementation in the USAF will require continued education and training of primary care providers to improve knowledge and mitigate concerns about PrEP. PMID:27512869

Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine HIV pre-exposure prophylaxis: clinical guidelines. Update April 2018.

PubMed

Wright, Edwina; Grulich, Andrew; Roy, Katy; Boyd, Mark; Cornelisse, Vincent; Russell, Darren; O'Donnell, Darryl; Whittaker, Bill; Crooks, Levinia; Zablotska, Iryna

2018-04-01

Daily use of coformulated tenofovir and emtricitabine for HIV pre-exposure prophylaxis (PrEP) by populations at high risk of HIV infection is now recommended in guidelines from the United States, Europe and Australia and globally through the 2015 WHO guidelines. These 2017 Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine's (ASHM) PrEP Guidelines are an updated adaptation of the 2014 US Centers for Disease Control's PrEP guidelines and are designed to: •Support the prescription of PrEP using forms of coformulated tenofovir and emtricitabine that have been registered in Australia by the Therapeutic Goods Administration and other bioequivalent generic drugs that are available in Australia through self-importation, private prescription or Australian PrEP clinical trials•Assist clinicians in the evaluation of patients who are seeking PrEP•Assist clinicians in commencing and monitoring patients on PrEP including PrEP dosing schedules, management of side-effects and toxicity, use of PrEP in pregnancy and in chronic hepatitis B infection and how to cease PrEP Daily PrEP with co-formulated tenofovir and emtricitabine, used continuously or for shorter periods of time, is recommended in these guidelines as a key HIV-prevention option for men who have sex with men (MSM), transgender men and women, heterosexual men and women, and people who inject drugs (PWID) at substantial risk of HIV acquisition. These guidelines were updated in April 2018 and include changes to the recommendations regarding the choice of daily or on-demand PrEP.

Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells.

PubMed Central

Rogers, M; Yehiely, F; Scott, M; Prusiner, S B

1993-01-01

The only known component of the infectious prion is a posttranslationally modified protein known as the scrapie isoform of the prion protein, PrPSc. Upon limited proteolysis, a protease-resistant fragment designated PrP 27-30 is formed. Using in vitro mutagenesis, we examined the role of the N and C termini in the formation of PrPSc in persistently infected, mouse neuroblastoma (ScN2a) cells. Neither deletion of amino acids 23-88, which are also removed by proteinase K in the formation of PrP 27-30, nor deletion of the five octapeptide repeats within this region altered synthesis of PrPSc. Elongation of PrP with one, two, four, or six octapeptide repeats in addition to the five found in wild-type PrP did not alter the synthesis of PrPSc. Truncation of the C terminus was accomplished by substituting a translation stop codon for the predicted glycosylinositol phospholipid (GPI) anchor-attachment signal corresponding to amino acids 231-254. Expression of this C-terminal PrP mutant in ScN2a cells produced PrPSc that appeared to lack a GPI anchor. We conclude that neither the GPI anchor nor the N-terminal 66 amino acids are required for the synthesis of PrPSc as measured by the acquisition of limited resistance to proteinase K digestion. Whether these truncated or elongated PrP molecules are competent to participate in the formation of infectious prions remains to be established. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8475059

Awareness, discussion and non-prescribed use of HIV pre-exposure prophylaxis among persons living with HIV/AIDS in Italy: a Nationwide, cross-sectional study among patients on antiretrovirals and their treating HIV physicians.

PubMed

Palummieri, Antonio; De Carli, Gabriella; Rosenthal, Éric; Cacoub, Patrice; Mussini, Cristina; Puro, Vincenzo

2017-11-28

Before Pre-Exposure Prophylaxis (PrEP) was officially recommended and made available, a few surveys among gay and bisexual men, and persons living with HIV/AIDS (PLWHA), identified an informal use of antiretrovirals (ARVs) for PrEP among HIV-negative individuals. Before PrEP availability in Italy, we aimed to assess whether PLWHA in Italy shared their ARVs with HIV-negative individuals, whether they knew people who were on PrEP, and describe the level of awareness and discussion on this preventive measure among them and people in their close circle. Two anonymous questionnaires investigating personal characteristics and PrEP awareness, knowledge, and experience were proposed to HIV specialists and their patients on ARVs in a one-week, cross-sectional survey (December 2013-January 2014). Among PLWHA, a Multivariable Logistic Regression analysis was conducted to identify factors associated with PrEP discussion with peers (close circle and/or HIV associations), and experience (use in close circle and/or personal ARV sharing). Eighty-seven specialists in 31 representative Infectious Diseases departments administered the questionnaire to 1405 PLWHA. Among specialists, 98% reported awareness, 65% knew the dosage schedule, and 14% had previously suggested or prescribed PrEP. Among PLWHA, 45.6% were somehow aware, discussed or had direct or indirect experience of PrEP: 38% "had heard" of PrEP, 24% were aware of studies in HIV-negative individuals demonstrating a risk reduction through the use of ARVs, 22% had discussed PrEP, 12% with peers; 9% reported PrEP use in close circle and 1% personal ARV sharing. Factors predictive of either PrEP discussion with peers or experience differed between men and women, but across all genders were mainly related to having access to information, with HIV association membership being the strongest predictor. At a time and place where there were neither official information nor proposals or interventions to guide public policies on PrEP in Italy, a significant number of PLWHA were aware of it, and approximately 10% reported PrEP use in their close circle, although they rarely shared their ARVs with uninfected people for this purpose. Official policies and PrEP availability, along with implementation programs, could avoid risks from uncontrolled PrEP procurement and self-administration practices.

Characterization of SNPs Associated with Prostate Cancer in Men of Ashkenazic Descent from the Set of GWAS Identified SNPs: Impact of Cancer Family History and Cumulative SNP Risk Prediction

PubMed Central

Agalliu, Ilir; Wang, Zhaoming; Wang, Tao; Dunn, Anne; Parikh, Hemang; Myers, Timothy

2013-01-01

Background Genome-wide association studies (GWAS) have identified multiple SNPs associated with prostate cancer (PrCa). Population isolates may have different sets of risk alleles for PrCa constituting unique population and individual risk profiles. Methods To test this hypothesis, associations between 31 GWAS SNPs of PrCa were examined among 979 PrCa cases and 1,251 controls of Ashkenazic descent using logistic regression. We also investigated risks by age at diagnosis, pathological features of PrCa, and family history of cancer. Moreover, we examined associations between cumulative number of risk alleles and PrCa and assessed the utility of risk alleles in PrCa risk prediction by comparing the area under the curve (AUC) for different logistic models. Results Of the 31 genotyped SNPs, 8 were associated with PrCa at p≤0.002 (corrected p-value threshold) with odds ratios (ORs) ranging from 1.22 to 1.42 per risk allele. Four SNPs were associated with aggressive PrCa, while three other SNPs showed potential interactions for PrCa by family history of PrCa (rs8102476; 19q13), lung cancer (rs17021918; 4q22), and breast cancer (rs10896449; 11q13). Men in the highest vs. lowest quartile of cumulative number of risk alleles had ORs of 3.70 (95% CI 2.76–4.97); 3.76 (95% CI 2.57–5.50), and 5.20 (95% CI 2.94–9.19) for overall PrCa, aggressive cancer and younger age at diagnosis, respectively. The addition of cumulative risk alleles to the model containing age at diagnosis and family history of PrCa yielded a slightly higher AUC (0.69 vs. 0.64). Conclusion These data define a set of risk alleles associated with PrCa in men of Ashkenazic descent and indicate possible genetic differences for PrCa between populations of European and Ashkenazic ancestry. Use of genetic markers might provide an opportunity to identify men at highest risk for younger age of onset PrCa; however, their clinical utility in identifying men at highest risk for aggressive cancer remains limited. PMID:23573233

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

USGS Publications Warehouse

Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

2013-01-01

Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human and macaque blood.

Gesture controlled human-computer interface for the disabled.

PubMed

Szczepaniak, Oskar M; Sawicki, Dariusz J

2017-02-28

The possibility of using a computer by a disabled person is one of the difficult problems of the human-computer interaction (HCI), while the professional activity (employment) is one of the most important factors affecting the quality of life, especially for disabled people. The aim of the project has been to propose a new HCI system that would allow for resuming employment for people who have lost the possibility of a standard computer operation. The basic requirement was to replace all functions of a standard mouse without the need of performing precise hand movements and using fingers. The Microsoft's Kinect motion controller had been selected as a device which would recognize hand movements. Several tests were made in order to create optimal working environment with the new device. The new communication system consisted of the Kinect device and the proper software had been built. The proposed system was tested by means of the standard subjective evaluations and objective metrics according to the standard ISO 9241-411:2012. The overall rating of the new HCI system shows the acceptance of the solution. The objective tests show that although the new system is a bit slower, it may effectively replace the computer mouse. The new HCI system fulfilled its task for a specific disabled person. This resulted in the ability to return to work. Additionally, the project confirmed the possibility of effective but nonstandard use of the Kinect device. Med Pr 2017;68(1):1-21. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Daily short message service surveys to measure sexual behavior and pre-exposure prophylaxis use among Kenyan men and women.

PubMed

Curran, Kathryn; Mugo, Nelly R; Kurth, Ann; Ngure, Kenneth; Heffron, Renee; Donnell, Deborah; Celum, Connie; Baeten, Jared M

2013-11-01

Pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy which requires high adherence. We tested the use of daily short message service (i.e., SMS/text message) surveys to measure sexual behavior and PrEP adherence in Kenya. Ninety-six HIV-uninfected adult individuals, taking daily oral PrEP in a clinical trial, received daily SMS surveys for 60 days. Most participants (96.9 %) reported taking PrEP on ≥80 % days, but 69.8 % missed at least one dose. Unprotected sex was reported on 4.9 % of days; however, 47.9 % of participants reported unprotected sex at least once. Unprotected sex was not correlated with PrEP use (OR = 0.95). Participants reporting more sex were less likely to report PrEP non-adherence and those reporting no sex were most likely to report missing a PrEP dose (adjusted OR = 1.87). PrEP adherence was high, missed doses were correlated with sexual abstinence, and unprotected sex was not associated with decreased PrEP adherence.

The pathological prion protein forms ionic conductance in lipid bilayer.

PubMed

Paulis, Daniele; Maras, Bruno; Schininà, M Eugenia; di Francesco, Laura; Principe, Serena; Galeno, Roberta; Abdel-Haq, Hanin; Cardone, Franco; Florio, Tullio; Pocchiari, Maurizio; Mazzanti, Michele

2011-08-01

Transmissible spongiform encephalopathies (TSEs) are neurodegenerative pathologies characterized by the accumulation of amyloid fibrils mainly composed of the pathological isoform of the prion protein (PrP(TSE)). PrP(TSE) pre-amyloid fibrils are supposed to induce neurodegenerative lesions possibly through the alteration of membrane permeability. The effect of PrP(TSE) on cellular membranes has been modeled in vitro by synthetic peptides that are, however, only partially representative of PrP(TSE) isoforms found in vivo. In the present work we show that a synthetic membrane exposed to PrP27-30 extracted from TSE-infected hamster brains changes its permeability because of the formation of molecular pores that alter the conductance of the synthetic lipid bilayer. Synthetic membrane challenged with the recombinant prion peptide PrP90-231 shows a much lower conductance. Elevation of calcium ion concentration not only increases the current amplitude due to the action of both PrP27-30 and PrP90-231 on the membrane, but also amplifies the interaction of PrP90-231 with the lipid bilayer. Copyright © 2011 Elsevier B.V. All rights reserved.

Enthalpies of formation of Cd–Pr intermetallic compounds and thermodynamic assessment of the Cd–Pr system

PubMed Central

Reichmann, Thomas L.; Richter, Klaus W.; Delsante, Simona; Borzone, Gabriella; Ipser, Herbert

2014-01-01

In the present study standard enthalpies of formation were measured by reaction and solution calorimetry at stoichiometric compositions of Cd2Pr, Cd3Pr, Cd58Pr13 and Cd6Pr. The corresponding values were determined to be −46.0, −38.8, −35.2 and −24.7 kJ/mol(at), respectively. These data together with thermodynamic data and phase diagram information from literature served as input data for a CALPHAD-type optimization of the Cd–Pr phase diagram. The complete composition range could be described precisely with the present models, both with respect to phase equilibria as well as to thermodynamic input data. The thermodynamic parameters of all intermetallic compounds were modelled following Neumann–Kopp rule. Temperature dependent contributions to the individual Gibbs energies were used for all compounds. Extended solid solubilities are well described for the low- and high-temperature modifications of Pr and also for the intermetallic compound CdPr. A quite good agreement with all viable data available from literature was found and is presented. PMID:25540475

Infectivity-associated PrP(Sc) and disease duration-associated PrP(Sc) of mouse BSE prions.

PubMed

Miyazawa, Kohtaro; Okada, Hiroyuki; Masujin, Kentaro; Iwamaru, Yoshifumi; Yokoyama, Takashi

2015-01-01

Disease-related prion protein (PrP(Sc)), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrP(Sc) in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrP(Sc) in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrP(Sc) was precipitated into the pellet, and the supernatant contained only a slight amount of PrP(Sc). Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrP(Sc) may be responsible for prion infectivity and that large, aggregated PrP(Sc) may contribute to determining prion disease duration.

Infectivity-associated PrPSc and disease duration-associated PrPSc of mouse BSE prions

PubMed Central

Miyazawa, Kohtaro; Okada, Hiroyuki; Masujin, Kentaro; Iwamaru, Yoshifumi; Yokoyama, Takashi

2015-01-01

ABSTRACT Disease-related prion protein (PrPSc), which is a structural isoform of the host-encoded cellular prion protein, is thought to be a causative agent of transmissible spongiform encephalopathies. However, the specific role of PrPSc in prion pathogenesis and its relationship to infectivity remain controversial. A time-course study of prion-affected mice was conducted, which showed that the prion infectivity was not simply proportional to the amount of PrPSc in the brain. Centrifugation (20,000 ×g) of the brain homogenate showed that most of the PrPSc was precipitated into the pellet, and the supernatant contained only a slight amount of PrPSc. Interestingly, mice inoculated with the obtained supernatant showed incubation periods that were approximately 15 d longer than those of mice inoculated with the crude homogenate even though both inocula contained almost the same infectivity. Our results suggest that a small population of fine PrPSc may be responsible for prion infectivity and that large, aggregated PrPSc may contribute to determining prion disease duration. PMID:26555211

A study of structure of phenomenology of consciousness in meditative and non-meditative states.

PubMed

Venkatesh, S; Raju, T R; Shivani, Y; Tompkins, G; Meti, B L

1997-04-01

Twelve senior Kundalini (Chakra) meditators were assessed during meditation session and non-meditation or control session using Phenomenology of Consciousness Inventory. The data has been analyzed using structural analysis to measure the altered state of consciousness and the identity state by comparing meditative state with non-meditative state. The structural analysis of pattern of consciousness during the meditative state revealed altered experience in perception (percentile rank PR = 90), meaning (PR = 82) and time sense (PR = 87), while positive affect dimension showed increased joy (PR = 73) and love (PR = 67). The imagery vividness (PR = 72), self-awareness (PR = 77), rationality (PR = 73) and arousal (PR = 69) were found to be structurally different from the ordinary state. With regards to identity state meditative experience was found to produce statistically significant changes in terms of intensity in meaning (P < 0.05), time sense (P < 0.05), joy (P < 0.05), love (P < 0.05) and state of awareness (P < 0.01). Our results indicate that long term practice of meditation appears to produce structural as well as intensity changes in phenomenological experiences of consciousness.

Heat and momentum transport scalings in vertical convection

NASA Astrophysics Data System (ADS)

Shishkina, Olga

2016-11-01

For vertical convection, where a fluid is confined between two differently heated isothermal vertical walls, we investigate the heat and momentum transport, which are measured, respectively, by the Nusselt number Nu and the Reynolds number Re . For laminar vertical convection we derive analytically the dependence of Re and Nu on the Rayleigh number Ra and the Prandtl number Pr from our boundary layer equations and find two different scaling regimes: Nu Pr 1 / 4 Ra 1 / 4 , Re Pr - 1 / 2 Ra 1 / 2 for Pr << 1 and Nu Pr0 Ra 1 / 4 , Re Pr-1 Ra 1 / 2 for Pr >> 1 . Direct numerical simulations for Ra from 105 to 1010 and Pr from 0.01 to 30 are in excellent ageement with our theoretical findings and show that the transition between the regimes takes place for Pr around 0.1. We summarize the results from and present new theoretical and numerical results for transitional and turbulent vertical convection. The work is supported by the Deutsche Forschungsgemeinschaft (DFG) under the Grant Sh 405/4 - Heisenberg fellowship.

Knowledge of Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Men Who Have Sex with Men in Denver, Colorado

PubMed Central

Al-Tayyib, Alia A.; Thrun, Mark W.; Haukoos, Jason S.; Walls, N. Eugene

2014-01-01

As part of the National HIV Behavioral Surveillance System among men who have sex with men (MSM) in Denver, Colorado, we assessed knowledge of pre-exposure prophylaxis (PrEP); willingness to use PrEP; and potential changes in risk behaviors among HIV-negative participants reporting sexual activity with a male partner in the preceding 12 months. We examined knowledge of PrEP before (2008) and after (2011) results of the iPrEx trial were available. Of the 425 participants in the 2008 sample, 91 (21 %) were aware of PrEP compared to 131 (28 %) of the 461 participants in the 2011 sample (adjusted prevalence ratio: 1.43, 95 % confidence interval: 1.18, 1.72). Despite the increase in 2011, few MSM in Denver were aware of PrEP. Educating high-risk MSM about the potential utility of PrEP as an adjunct to other effective prevention methods is needed when considering the addition of PrEP to the HIV prevention arsenal. PMID:23824227

Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity

PubMed Central

Nicoll, Andrew J.; Panico, Silvia; Freir, Darragh B.; Wright, Daniel; Terry, Cassandra; Risse, Emmanuel; Herron, Caroline E.; O’Malley, Tiernan; Wadsworth, Jonathan D. F.; Farrow, Mark A.; Walsh, Dominic M.; Saibil, Helen R.; Collinge, John

2013-01-01

Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-β protein (Aβ) have important roles in Alzheimer’s disease with toxicities mimicked by synthetic Aβ1–42. However, no defined toxic structures acting via specific receptors have been identified and roles of proposed receptors, such as prion protein (PrP), remain controversial. Here we quantify binding to PrP of Aβ1–42 after different durations of aggregation. We show PrP-binding and PrP-dependent inhibition of long-term potentiation (LTP) correlate with the presence of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain transient Aβ assemblies cause PrP-dependent toxicity explains conflicting reports regarding the involvement of PrP in Aβ-induced impairments. We show that these protofibrils contain a defined nanotubular structure with a previously unidentified triple helical conformation. Blocking the formation of Aβ nanotubes or their interaction with PrP might have a role in treatment of Alzheimer’s disease. PMID:24022506

History of dating violence and the association with late adolescent health

PubMed Central

2013-01-01

Background The present investigation expands upon prior studies by examining the relationship between health in late adolescence and the experience of physical/sexual and non-physical dating violence victimization, including dating violence types that are relevant to today’s adolescents (e.g., harassment via email and text messaging). We examined the relationship between physical/sexual and non-physical dating violence victimization from age 13 to 19 and health in late adolescence/early adulthood. Methods The sample comprised 585 subjects (ages 18 to 21; mean age, 19.8, SD = 1.0) recruited from The Ohio State University who completed an online survey to assess: 1) current health (depression, disordered eating, binge drinking, smoking, and frequent sexual behavior); and 2) dating violence victimization from age 13 to 19 (retrospectively assessed using eight questions covering physical, sexual, and non-physical abuse, including technology-related abuse involving stalking/harassment via text messaging and email). Multivariable models compared health indicators in never-exposed subjects to those exposed to physical/sexual or non-physical dating violence only. The multivariable models were adjusted for age and other non-dating abuse victimization (bullying; punched, kicked, choked by a parent/guardian; touched in a sexual place, forced to touch someone sexually). Results In adjusted analyses, compared to non-exposed females, females with physical/sexual dating violence victimization were at increased risk of smoking (prevalence ratio = 3.95); depressive symptoms (down/hopeless, PR = 2.00; lost interest, PR = 1.79); eating disorders (using diet aids, PR = 1.98; fasting, PR = 4.71; vomiting to lose weight, PR = 4.33); and frequent sexual behavior (5+ intercourse and oral sex partners, PR = 2.49, PR = 2.02; having anal sex, PR = 2.82). Compared to non-exposed females, females with non-physical dating violence only were at increased risk of smoking (PR = 3.61), depressive symptoms (down/hopeless, PR = 1.41; lost interest, PR = 1.36), eating disorders (fasting, PR = 3.37; vomiting, PR = 2.66), having 5+ intercourse partners (PR = 2.20), and having anal sex (PR = 2.18). For males, no health differences were observed for those experiencing physical/sexual dating violence compared to those who did not. Compared to non-exposed males, males with non-physical dating violence only were at increased risk of smoking (PR = 3.91) and disordered eating (fasting, using diet aids, vomiting, PR = 2.93). Conclusions For females, more pronounced adverse health was observed for those exposed to physical/sexual versus non-physical dating violence. For both females and males, non-physical dating violence victimization contributed to poor health. PMID:24015863

Process solutions for reducing PR residue over non-planar wafer

NASA Astrophysics Data System (ADS)

Lin, C. H.; Huang, C. H.; Yang, Elvis; Yang, T. H.; Chen, K. C.; Lu, Chih-Yuan

2011-03-01

SAS (Self-Aligned Source) process has been widely adopted on manufacturing NOR Flash devices. To form the SAS structure, the compromise between small space patterning and sufficiently removing photo resist residue in topographical substrate has been a critical challenge as the device scaling down. In this study, photo simulation, layout optimization, resist processing and tri-layer materials were evaluated to form defect-free and highly extendible SAS structure for NOR Flash devices. Photo simulation suggested more coherent light source allowed the incident light to reach the trench bottom that facilitates the removal of photo resist. Mask bias also benefited the process latitude extension for residue-free SAS printing. In the photo resist processing, both lowering the SB (Soft Bake) and raising PEB (Post-Exposure Bake) temperature of photo resist were helpful to broaden the process window but the final pattern profile was not good enough. Thermal flow for pos-exposure pattern shrinkage achieved small CD (Critical Dimension) patterning with residue-free, however the materials loading effect is another issue to be addressed at memory array boundary. Tri-layer scheme demonstrated good results in terms of free from residue, better substrate reflectivity control, enabling smaller space printing to loosen overlay specification and minimizing the poly gate clipping defect. It was finally proposed to combine with etch effort to from the SAS structure. Besides it is also promising to extend to even smaller technology nodes.

Dielectric Constant and Loss Data. Part 4

DTIC Science & Technology

1980-12-01

Fluorinated ethers, Organic Chemicals Dept., P.R.-194Dow Chemical "Dowtherm" A, P.R.-194 T ORg C a p - Dew Corning Corp., IV-26, 27, 41, 42, "HVITON...Esso "Teresso" oil, V-78; P.R.-195 and MFl16, V-15 "Estawax", IV-57 "Eccosorb" MFll7, V-15, 242 Ethers, fluorinated , P.R.-194 Eggwhite. P.R.-202 "Ethocel...PPG, 8-20 Flourglas laminate, 9-33 "Gafite" cast polymer, IV-34 Fluorinated ethers, P.R.-194 Gasoline, aviation, 100 and 91 octane, Fluorcarbon

The prion-ZIP connection: From cousins to partners in iron uptake

PubMed Central

Singh, Neena; Asthana, Abhishek; Baksi, Shounak; Desai, Vilok; Haldar, Swati; Hari, Sahi; Tripathi, Ajai K

2015-01-01

ABSTRACT Converging observations from disparate lines of inquiry are beginning to clarify the cause of brain iron dyshomeostasis in sporadic Creutzfeldt-Jakob disease (sCJD), a neurodegenerative condition associated with the conversion of prion protein (PrPC), a plasma membrane glycoprotein, from α-helical to a β-sheet rich PrP-scrapie (PrPSc) isoform. Biochemical evidence indicates that PrPC facilitates cellular iron uptake by functioning as a membrane-bound ferrireductase (FR), an activity necessary for the transport of iron across biological membranes through metal transporters. An entirely different experimental approach reveals an evolutionary link between PrPC and the Zrt, Irt-like protein (ZIP) family, a group of proteins involved in the transport of zinc, iron, and manganese across the plasma membrane. Close physical proximity of PrPC with certain members of the ZIP family on the plasma membrane and increased uptake of extracellular iron by cells that co-express PrPC and ZIP14 suggest that PrPC functions as a FR partner for certain members of this family. The connection between PrPC and ZIP proteins therefore extends beyond common ancestry to that of functional cooperation. Here, we summarize evidence supporting the facilitative role of PrPC in cellular iron uptake, and implications of this activity on iron metabolism in sCJD brains. PMID:26689487

Cryo-immunogold electron microscopy for prions: toward identification of a conversion site.

PubMed

Godsave, Susan F; Wille, Holger; Kujala, Pekka; Latawiec, Diane; DeArmond, Stephen J; Serban, Ana; Prusiner, Stanley B; Peters, Peter J

2008-11-19

Prion diseases are caused by accumulation of an abnormally folded isoform (PrP(Sc)) of the cellular prion protein (PrP(C)). The subcellular distribution of PrP(Sc) and the site of its formation in brain are still unclear. We performed quantitative cryo-immunogold electron microscopy on hippocampal sections from mice infected with the Rocky Mountain Laboratory strain of prions. Two antibodies were used: R2, which recognizes both PrP(C) and PrP(Sc); and F4-31, which only detects PrP(C) in undenatured sections. At a late subclinical stage of prion infection, both PrP(C) and PrP(Sc) were detected principally on neuronal plasma membranes and on vesicles resembling early endocytic or recycling vesicles in the neuropil. The R2 labeling was approximately six times higher in the infected than the uninfected hippocampus and gold clusters were only evident in infected tissue. The biggest increase in labeling density (24-fold) was found on the early/recycling endosome-like vesicles of small-diameter neurites, suggesting these as possible sites of conversion. Trypsin digestion of infected hippocampal sections resulted in a reduction in R2 labeling of >85%, which suggests that a high proportion of PrP(Sc) may be oligomeric, protease-sensitive PrP(Sc).

The role of the unusual threonine string in the conversion of prion protein.

PubMed

Abskharon, Romany; Wang, Fei; Vander Stel, Kayla J; Sinniah, Kumar; Ma, Jiyan

2016-12-16

The conversion of normal prion protein (PrP) into pathogenic PrP conformers is central to prion disease, but the mechanism remains unclear. The α-helix 2 of PrP contains a string of four threonines, which is unusual due to the high propensity of threonine to form β-sheets. This structural feature was proposed as the basis for initiating PrP conversion, but experimental results have been conflicting. We studied the role of the threonine string on PrP conversion by analyzing mouse Prnp a and Prnp b polymorphism that contains a polymorphic residue at the beginning of the threonine string, and PrP mutants in which threonine 191 was replaced by valine, alanine, or proline. The PMCA (protein misfolding cyclic amplification) assay was able to recapitulate the in vivo transmission barrier between PrP a and PrP b . Relative to PMCA, the amyloid fibril growth assay is less restrictive, but it did reflect certain properties of in vivo prion transmission. Our results suggest a plausible theory explaining the apparently contradictory results in the role of the threonine string in PrP conversion and provide novel insights into the complicated relationship among PrP stability, seeded conformational change, and prion structure, which is critical for understanding the molecular basis of prion infectivity.

Cuticle-degrading proteases produced by the entomopathogenic fungus Beauveria bassiana in the presence of coffee berry borer cuticle

PubMed Central

Dias, B.A.; Neves, P.M.O.J.; Furlaneto-Maia, L.; Furlaneto, M.C.

2008-01-01

A Brazilian isolate of Beauveria bassiana (CG425) that shows high virulence against the coffee berry borer (CBB) was examined for the production of subtilisin-like (Pr1) and trypsin-like (Pr2) cuticle-degrading proteases. Fungal growth was either in nitrate-medium or in CBB cuticle-containing medium under both buffered and unbuffered conditions. In unbuffered medium supplemented with cuticle, the pH of cultures dropped and Pr1 and Pr2 activities were detected in high amounts only at a pH of 5.5 or higher. In buffered cultures, Pr1 and Pr2 activities were higher in medium supplemented with cuticle compared to activities with nitrate-medium. The Pr1 and Pr2 activities detected were mostly in the culture supernatant. These data suggest that Pr1 and Pr2 proteases produced by strain CG425 are induced by components of CBB cuticle, and that the culture pH influences the expression of these proteases, indicating the occurrence of an efficient mechanism of protein secretion in this fungus. The results obtained in this study extend the knowledge about protease production in B. bassiana CG425, opening new avenues for studying the role of secreted proteases in virulence against the coffee berry borer during the infection process. PMID:24031220

The Importance of Sexual History Taking for PrEP Comprehension Among Young People of Color.

PubMed

Golub, Sarit A; Gamarel, Kristi E; Lelutiu-Weinberger, Corina

2017-05-01

Despite demonstrated efficacy, uptake of pre-exposure prophylaxis (PrEP) remains low, especially among highest priority populations. This study examined four PrEP messaging factors hypothesized to impact comprehension of PrEP educational information: (1) modality (video versus in-person message delivery); (2) frame (risk versus health focus); (3) specificity (gist versus verbatim efficacy information); and (4) sexual history (administered either before or after PrEP education). We examined message comprehension among 157 young people of color (YPoC) eligible for PrEP, using a series of multiple choice questions. Overall, 65.6 % (n = 103) got all message comprehension questions correct. In multivariate analyses, engaging in a sexual history before receiving PrEP education was associated with increased odds of message comprehension (aOR 2.23; 95 % CI 1.06-4.72). This effect was even stronger among those who received PrEP education via video (aOR 3.53; 95 % CI 1.16-10.81) compared to via health educator. This research underscores the importance of sexual history-taking as part of PrEP education and clinical practice for YPoC, and suggests that engaging patients in a sexual history prior to providing them with PrEP education may be key to increasing comprehension.

Analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides.

PubMed

Guichard, Cécile; Ivanyi-Nagy, Roland; Sharma, Kamal Kant; Gabus, Caroline; Marc, Daniel; Mély, Yves; Darlix, Jean-Luc

2011-10-01

Prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (PrP(C)) into the aggregated misfolded scrapie isoform, named PrP(Sc). Recent studies on the physiological role of PrP(C) revealed that this protein has probably multiple functions, notably in cell-cell adhesion and signal transduction, and in assisting nucleic acid folding. In fact, in vitro findings indicated that the human PrP (huPrP) possesses nucleic acid binding and annealing activities, similarly to nucleic acid chaperone proteins that play essential roles in cellular DNA and RNA metabolism. Here, we show that a peptide, representing the N-terminal domain of huPrP, facilitates nucleic acid annealing by two parallel pathways nucleated through the stem termini. We also show that PrP of human or ovine origin facilitates DNA strand exchange, ribozyme-directed cleavage of an RNA template and RNA trans-splicing in a manner similar to the nucleocapsid protein of HIV-1. In an attempt to characterize inhibitors of PrP-chaperoning in vitro we discovered that the thioaptamer 5'-GACACAAGCCGA-3' was extensively inhibiting the PrP chaperoning activities. At the same time a recently characterized methylated oligoribonucleotide inhibiting the chaperoning activity of the HIV-1 nucleocapsid protein was poorly impairing the PrP chaperoning activities.

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing

NASA Astrophysics Data System (ADS)

Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling

2016-10-01

Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.

High-affinity copper transport and Snq2 export permease of saccharomyces cerevisiae modulate cytotoxicity of PR-10 from Theobroma cacao.

PubMed

Pungartnik, Cristina; da Silva, Aline Clara; de Melo, Sarah Alves; Gramacho, Karina Peres; de Mattos Cascardo, Júlio Cézar; Brendel, Martin; Micheli, Fabienne; da Silva Gesteira, Abelmon

2009-01-01

A pathogenesis-related (PR) protein from Theobroma cacao (TcPR-10) was identified from a cacao-Moniliophthora perniciosa interaction cDNA library. Nucleotide and amino acid sequences showed homology with other PR-10 proteins having P loop motif and Betv1 domain. Recombinant TcPR-10 showed in vitro and in vivo ribonuclease activity, and antifungal activity against the basidiomycete cacao pathogen M. perniciosa and the yeast Saccharomyces cerevisiae. Fluorescein isothiocyanate-labeled TcPR-10 was internalized by M. perniciosa hyphae and S. cerevisiae cells and inhibited growth of both fungi. Energy and temperature-dependent internalization of the TcPR-10 suggested an active importation into the fungal cells. Chronical exposure to TcPR-10 of 29 yeast mutants with single gene defects in DNA repair, general membrane transport, metal transport, and antioxidant defenses was tested. Two yeast mutants were hyperresistant compared with their respective isogenic wild type: ctr3Delta mutant, lacking the high-affinity plasma membrane copper transporter and mac1Delta, the copper-sensing transcription factor involved in regulation of high-affinity copper transport. Acute exposure of exponentially growing yeast cells revealed that TcPR-10 resistance is also enhanced in the Snq2 export permease-lacking mutant which has reduced intracellular presence of TcPR-10.

A Ground Validation Network for the Global Precipitation Measurement Mission

NASA Technical Reports Server (NTRS)

Schwaller, Mathew R.; Morris, K. Robert

2011-01-01

A prototype Validation Network (VN) is currently operating as part of the Ground Validation System for NASA's Global Precipitation Measurement (GPM) mission. The VN supports precipitation retrieval algorithm development in the GPM prelaunch era. Postlaunch, the VN will be used to validate GPM spacecraft instrument measurements and retrieved precipitation data products. The period of record for the VN prototype starts on 8 August 2006 and runs to the present day. The VN database includes spacecraft data from the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) and coincident ground radar (GR) data from operational meteorological networks in the United States, Australia, Korea, and the Kwajalein Atoll in the Marshall Islands. Satellite and ground radar data products are collected whenever the PR satellite track crosses within 200 km of a VN ground radar, and these data are stored permanently in the VN database. VN products are generated from coincident PR and GR observations when a significant rain event occurs. The VN algorithm matches PR and GR radar data (including retrieved precipitation data in the case of the PR) by calculating averages of PR reflectivity (both raw and attenuation corrected) and rain rate, and GR reflectivity at the geometric intersection of the PR rays with the individual GR elevation sweeps. The algorithm thus averages the minimum PR and GR sample volumes needed to "matchup" the spatially coincident PR and GR data types. The result of this technique is a set of vertical profiles for a given rainfall event, with coincident PR and GR samples matched at specified heights throughout the profile. VN data can be used to validate satellite measurements and to track ground radar calibration over time. A comparison of matched TRMM PR and GR radar reflectivity factor data found a remarkably small difference between the PR and GR radar reflectivity factor averaged over this period of record in stratiform and convective rain cases when samples were taken from high in the atmosphere. A significant difference in PR and GR reflectivity was found in convective cases, particularly in convective samples from the lower part of the atmosphere. In this case, the mean difference between PR and corrected GR reflectivity was -1.88 dBZ. The PR-GR bias was found to increase with the amount of PR attenuation correction applied, with the PR-GR bias reaching -3.07 dBZ in cases where the attenuation correction applied is greater than 6 dBZ. Additional analysis indicated that the version 6 TRMM PR retrieval algorithm underestimates rainfall in case of convective rain in the lower part of the atmosphere by 30%-40%.

PrEP as a feature in the optimal landscape of combination HIV prevention in sub-Saharan Africa

PubMed Central

McGillen, Jessica B; Anderson, Sarah-Jane; Hallett, Timothy B

2016-01-01

Introduction The new WHO guidelines recommend offering pre-exposure prophylaxis (PrEP) to people who are at substantial risk of HIV infection. However, where PrEP should be prioritised, and for which population groups, remains an open question. The HIV landscape in sub-Saharan Africa features limited prevention resources, multiple options for achieving cost saving, and epidemic heterogeneity. This paper examines what role PrEP should play in optimal prevention in this complex and dynamic landscape. Methods We use a model that was previously developed to capture subnational HIV transmission in sub-Saharan Africa. With this model, we can consider how prevention funds could be distributed across and within countries throughout sub-Saharan Africa to enable optimal HIV prevention (that is, avert the greatest number of infections for the lowest cost). Here, we focus on PrEP to elucidate where, and to whom, it would optimally be offered in portfolios of interventions (alongside voluntary medical male circumcision, treatment as prevention, and behaviour change communication). Over a range of continental expenditure levels, we use our model to explore prevention patterns that incorporate PrEP, exclude PrEP, or implement PrEP according to a fixed incidence threshold. Results At low-to-moderate levels of total prevention expenditure, we find that the optimal intervention portfolios would include PrEP in only a few regions and primarily for female sex workers (FSW). Prioritisation of PrEP would expand with increasing total expenditure, such that the optimal prevention portfolios would offer PrEP in more subnational regions and increasingly for men who have sex with men (MSM) and the lower incidence general population. The marginal benefit of including PrEP among the available interventions increases with overall expenditure by up to 14% (relative to excluding PrEP). The minimum baseline incidence for the optimal offer of PrEP declines for all population groups as expenditure increases. We find that using a fixed incidence benchmark to guide PrEP decisions would incur considerable losses in impact (up to 7%) compared with an approach that uses PrEP more flexibly in light of prevailing budget conditions. Conclusions Our findings suggest that, for an optimal distribution of prevention resources, choices of whether to implement PrEP in subnational regions should depend on the scope for impact of other possible interventions, local incidence in population groups, and total resources available. If prevention funding were to become restricted in the future, it may be suboptimal to use PrEP according to a fixed incidence benchmark, and other prevention modalities may be more cost-effective. In contrast, expansions in funding could permit PrEP to be used to its full potential in epidemiologically driven prevention portfolios and thereby enable a more cost-effective HIV response across Africa. PMID:27760682

A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers

PubMed Central

Noble, Geoffrey P.; Wang, Daphne W.; Walsh, Daniel J.; Barone, Justin R.; Miller, Michael B.; Nishina, Koren A.; Li, Sheng; Supattapone, Surachai

2015-01-01

Infectious prions contain a self-propagating, misfolded conformer of the prion protein termed PrPSc. A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious. However, some autocatalytic recombinant PrPSc molecules have low or undetectable levels of specific infectivity in bioassays, and the essential determinants of recombinant prion infectivity remain obscure. To identify structural and functional features specifically associated with infectivity, we compared the properties of two autocatalytic recombinant PrP conformers derived from the same original template, which differ by >105-fold in specific infectivity for wild-type mice. Structurally, hydrogen/deuterium exchange mass spectrometry (DXMS) studies revealed that solvent accessibility profiles of infectious and non-infectious autocatalytic recombinant PrP conformers are remarkably similar throughout their protease-resistant cores, except for two domains encompassing residues 91-115 and 144-163. Raman spectroscopy and immunoprecipitation studies confirm that these domains adopt distinct conformations within infectious versus non-infectious autocatalytic recombinant PrP conformers. Functionally, in vitro prion propagation experiments show that the non-infectious conformer is unable to seed mouse PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor, including native PrPC. Taken together, these results indicate that having a conformation that can be specifically adopted by post-translationally modified PrPC molecules is an essential determinant of biological infectivity for recombinant prions, and suggest that this ability is associated with discrete features of PrPSc structure. PMID:26125623

Lipid Rafts and Clathrin Cooperate in the Internalization of PrPC in Epithelial FRT Cells

PubMed Central

Casanova, Philippe; Puri, Claudia; Paladino, Simona; Tivodar, Simona S.; Campana, Vincenza; Tacchetti, Carlo; Zurzolo, Chiara

2009-01-01

Background The cellular prion protein (PrPC) plays a key role in the pathogenesis of Transmissible Spongiform Encephalopathies in which the protein undergoes post-translational conversion to the infectious form (PrPSc). Although endocytosis appears to be required for this conversion, the mechanism of PrPC internalization is still debated, as caveolae/raft- and clathrin-dependent processes have all been reported to be involved. Methodology/Principal Findings We have investigated the mechanism of PrPC endocytosis in Fischer Rat Thyroid (FRT) cells, which lack caveolin-1 (cav-1) and caveolae, and in FRT/cav-1 cells which form functional caveolae. We show that PrPC internalization requires activated Cdc-42 and is sensitive to cholesterol depletion but not to cav-1 expression suggesting a role for rafts but not for caveolae in PrPC endocytosis. PrPC internalization is also affected by knock down of clathrin and by the expression of dominant negative Eps15 and Dynamin 2 mutants, indicating the involvement of a clathrin-dependent pathway. Notably, PrPC co-immunoprecipitates with clathrin and remains associated with detergent-insoluble microdomains during internalization thus indicating that PrPC can enter the cell via multiple pathways and that rafts and clathrin cooperate in its internalization. Conclusions/Significance These findings are of particular interest if we consider that the internalization route/s undertaken by PrPC can be crucial for the ability of different prion strains to infect and to replicate in different cell lines. PMID:19503793

Poppers and PrEP: Use of Pre-exposure Prophylaxis Among Men Who Have Sex with Men Who Use Inhaled Nitrites.

PubMed

Hambrick, H Rhodes; Park, Su Hyun; Schneider, John A; Mayer, Kenneth H; Carrico, Adam W; Sherman, Scott E; Duncan, Dustin T

2018-05-09

Men who have sex with men (MSM) commonly use inhaled nitrites, or poppers, though their use is a risk factor HIV seroconversion. Pre-exposure prophylaxis, or PrEP, is effective for HIV prevention, but is not widely used, and little is known regarding PrEP use and acceptability among MSM who use inhaled nitrites. We surveyed 580 MSM in Paris, France in 2016 about popper use, sexual behaviors including condomless anal intercourse (CAI), serosorting, and sexual positioning, PrEP use, PrEP candidacy, and interest in alternate PrEP delivery modalities. We included 444 HIV negative participants for the current study. 46.2% reported popper use in the prior 3 months. Using multivariate adjusted logistic regression, we found that popper users were more likely than non-users to consider themselves candidates for PrEP [adjusted relative risk ratio (aRRR) = 2.73; 95% CI 1.54-4.83], but they were not more likely to be current (aRRR = 1.54; 95% CI 0.71-3.33) or past (aRRR = 1.37; 95% CI 0.44-4.28) PrEP users. Mediation analyses indicated that increased CAI and serosorting partly explained the relationship between popper use and PrEP candidacy. There was considerable interest in alternate proposed PrEP delivery modalities, particularly long-acting injectable PrEP [adjusted risk ratio (aRR) = 1.43; 95% CI 1.15-1.79].

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis.

PubMed

Millet, Arnaud; Martin, Katherine R; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

2015-11-02

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology.

Progesterone receptor expression during prostate cancer progression suggests a role of this receptor in stromal cell differentiation.

PubMed

Yu, Yue; Yang, Ou; Fazli, Ladan; Rennie, Paul S; Gleave, Martin E; Dong, Xuesen

2015-07-01

The progesterone receptor, like the androgen receptor, belongs to the steroid receptor superfamily. Our previous studies have reported that the PR is expressed specifically in prostate stroma. PR inhibits proliferation of, and regulates cytokine secretion by stromal cells. However, PR protein expression in cancer-associated stroma during prostate cancer progression has not been profiled. Since the phenotypes of prostate stromal cells change dynamically as tumors progress, whether the PR plays a role in regulating stromal cell differentiation needs to be investigated. Immunohistochemistry assays measured PR protein levels on human prostate tissue microarrays containing 367 tissue cores from benign prostate, prostate tumors with different Gleason scores, tumors under various durations of castration therapy, and tumors at the castration-resistant stage. Immunoblotting assays determined whether PR regulated the expression of alpha smooth muscle actin (α-SMA), vimentin, and fibroblast specific protein (FSP) in human prostate stromal cells. PR protein levels decreased in cancer-associated stroma when compared with that in benign prostate stroma. This reduction in PR expression was not correlated with Gleason scores. PR protein levels were elevated by castration therapy, but reduced to pre-castration levels when tumors progressed to the castration-resistant stage. Enhanced PR expression in human prostate stromal cells increased α-SMA, but decreased vimentin and FSP protein levels ligand-independently. These results suggest that PR plays an active role in regulating stromal cell phenotypes during prostate cancer progression. © 2015 Wiley Periodicals, Inc.

The Amino-Terminal PrP Domain Is Crucial to Modulate Prion Misfolding and Aggregation

PubMed Central

Cordeiro, Yraima; Kraineva, Julia; Gomes, Mariana P. B.; Lopes, Marilene H.; Martins, Vilma R.; Lima, Luís M. T. R.; Foguel, Débora; Winter, Roland; Silva, Jerson L.

2005-01-01

The main hypothesis for prion diseases is that the cellular protein (PrPC) can be altered into a misfolded, β-sheet-rich isoform (PrPSc), which undergoes aggregation and triggers the onset of transmissible spongiform encephalopathies. Here, we investigate the effects of amino-terminal deletion mutations, rPrPΔ51–90 and rPrPΔ32–121, on the stability and the packing properties of recombinant murine PrP. The region lacking in rPrPΔ51–90 is involved physiologically in copper binding and the other construct lacks more amino-terminal residues (from 32 to 121). The pressure stability is dramatically reduced with decreasing N-domain length and the process is not reversible for rPrPΔ51–90 and rPrPΔ32–121, whereas it is completely reversible for the wild-type form. Decompression to atmospheric pressure triggers immediate aggregation for the mutants in contrast to a slow aggregation process for the wild-type, as observed by Fourier-transform infrared spectroscopy. The temperature-induced transition leads to aggregation of all rPrPs, but the unfolding temperature is lower for the rPrP amino-terminal deletion mutants. The higher susceptibility to pressure of the amino-terminal deletion mutants can be explained by a change in hydration and cavity distribution. Taken together, our results show that the amino-terminal region has a pivotal role on the development of prion misfolding and aggregation. PMID:16040743

[Estrogen and progesterone receptors in normal cervix and primary cervical carcinoma].

PubMed

Shen, K; Yueng, W; Ngan, H

1994-05-01

Estrogen and progesterone receptor levels (ER and PR) were measured in 21 specimens of cervical carcinoma and in 17 normal cervix by monoclonal enzyme immunoassay (ER-EIA and PR-EIA). In normal cervix, 88.2% of specimens were ER-positive (more than 15 fmol/mg protein), 74.5% were PR-positive (more than 15 fmol/mg protein) and 74.5% were both ER and PR-positive. In cervical cancer, 66.7% of malignancies were ER-positive, 42.9% were PR-positive and 38.1% were both ER and PR-positive. There was no significant difference in ER status between the normal cervix and cervical cancer (P > 0.05), but PR status and levels in normal cervix were significantly higher than those in cervical carcinoma (P < 0.05). ER levels in squamous cell carcinoma was not correlated to the tumor stage, histologic grade and menopausal status. PR levels in premenopausal patients with squamous cell carcinoma were significantly higher than those in postmenopausal patients (P < 0.01). Adenocarcinoma of the cervix contained significantly more ER and PR than squamous cell carcinoma (P < 0.01, P < 0.05). In addition, serum E2 level was also assayed in 21 patients with cervical cancer. There was significant difference in E2 levels between the premenopausal and postmenopausal patients (P < 0.01). Patients were stratified according to E2 levels, a significant difference in PR level and in ratio of PR/ER was noted (P < 0.05, P < 0.01).

The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1.

PubMed

Gabus, C; Derrington, E; Leblanc, P; Chnaiderman, J; Dormont, D; Swietnicki, W; Morillas, M; Surewicz, W K; Marc, D; Nandi, P; Darlix, J L

2001-06-01

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases associated with the accumulation of a protease-resistant form of the prion protein (PrP). Although PrP is conserved in vertebrates, its function remains to be identified. In vitro PrP binds large nucleic acids causing the formation of nucleoprotein complexes resembling human immunodeficiency virus type 1 (HIV-1) nucleocapsid-RNA complexes and in vivo MuLV replication accelerates the scrapie infectious process, suggesting possible interactions between retroviruses and PrP. Retroviruses, including HIV-1 encode a major nucleic acid binding protein (NC protein) found within the virus where 2000 NC protein molecules coat the dimeric genome. NC is required in virus assembly and infection to chaperone RNA dimerization and packaging and in proviral DNA synthesis by reverse transcriptase (RT). In HIV-1, 5'-leader RNA/NC interactions appear to control these viral processes. This prompted us to compare and contrast the interactions of human and ovine PrP and HIV-1 NCp7 with HIV-1 5'-leader RNA. Results show that PrP has properties characteristic of NCp7 with respect to viral RNA dimerization and proviral DNA synthesis by RT. The NC-like properties of huPrP map to the N-terminal region of huPrP. Interestingly, PrP localizes in the membrane and cytoplasm of PrP-expressing cells. These findings suggest that PrP is a multifunctional protein possibly participating in nucleic acid metabolism.

Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis

PubMed Central

Millet, Arnaud; Martin, Katherine R.; Bonnefoy, Francis; Saas, Philippe; Mocek, Julie; Alkan, Manal; Terrier, Benjamin; Kerstein, Anja; Tamassia, Nicola; Satyanarayanan, Senthil Kumaran; Ariel, Amiram; Ribeil, Jean-Antoine; Guillevin, Loïc; Cassatella, Marco A.; Mueller, Antje; Thieblemont, Nathalie; Lamprecht, Peter; Mouthon, Luc; Perruche, Sylvain; Witko-Sarsat, Véronique

2015-01-01

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis that is associated with granulomatous inflammation and the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). We previously determined that PR3 on the surface of apoptotic neutrophils interferes with induction of antiinflammatory mechanisms following phagocytosis of these cells by macrophages. Here, we demonstrate that enzymatically active membrane-associated PR3 on apoptotic cells triggered secretion of inflammatory cytokines, including granulocyte CSF (G-CSF) and chemokines. This response required the IL-1R1/MyD88 signaling pathway and was dependent on the synthesis of NO, as macrophages from animals lacking these pathways did not exhibit a PR3-associated proinflammatory response. The PR3-induced microenvironment facilitated recruitment of inflammatory cells, such as macrophages, plasmacytoid DCs (pDCs), and neutrophils, which were observed in close proximity within granulomatous lesions in the lungs of GPA patients. In different murine models of apoptotic cell injection, the PR3-induced microenvironment instructed pDC-driven Th9/Th2 cell generation. Concomitant injection of anti-PR3 ANCAs with PR3-expressing apoptotic cells induced a Th17 response, revealing a GPA-specific mechanism of immune polarization. Accordingly, circulating CD4+ T cells from GPA patients had a skewed distribution of Th9/Th2/Th17. These results reveal that PR3 disrupts immune silencing associated with clearance of apoptotic neutrophils and provide insight into how PR3 and PR3-targeting ANCAs promote GPA pathophysiology. PMID:26436651

Contraceptives with novel benefits.

PubMed

Su, Ying; Lian, Qing-Quan; Ge, Ren-Shan

2012-01-01

Progesterone receptor (PR) agonists (progestins) and antagonists are developed for female contraceptives. However, non-contraceptive applications of newer progestins and PR modulators are being given more attention. The newer PR agonists including drospirenone, nomegestrol, trimegestone, dienogest and nestorone are being evaluated as contraceptives with health benefits because of their unique pharmacological properties. The selective PR modulators (SPRM; PR antagonists with PR agonistic properties) are under development not only for emergency contraception but also for other health benefits such as the treatment of endometritis and leiomyoma. After searching the literature from PubMed, clinicaltrials.gov and patent database, this review focuses on the effects and mechanisms of these progestins, and SPRMs as contraceptives with other health benefits. PR agonists and antagonists that have novel properties may generate better contraceptive effects with other health benefits.

Laser action of Pr3+ in LiYF4 and spectroscopy of Eu2+-sensitized Pr in BaY2F8

NASA Astrophysics Data System (ADS)

Knowles, David S.; Gabbe, David; Jenssen, H. P.; Zhang, Z.

1988-06-01

Laser action in flashlamp-pumped Pr:LiYF4 at room temperature is observed at 640 nm with a 15-J threshold, but only about 0.01 percent slope efficiency. Increased efficiency from sensitizing the Pr with Eu2+ is explored in the system Eu,Pr:BaY2F8. Codoped samples have been grown by the Czochralski growth method, and energy transfer between 2+ and Pr3+ is observed to be very weak. This is probably due to the poor overlap of the Eu2+ emission with the Pr3+ absorption lines, leading to the conclusion that hosts with a stronger crystal field at the Eu2+ site need to be identified.

Positron annihilation study of Y 1- xPr xBa 2Cu 3O 7

NASA Astrophysics Data System (ADS)

Zhao, Y. G.; Cao, B. S.; Yu, W. Z.; Du, Z. H.; Wang, Y. J.; Luo, C. Y.; Hu, H.; Wang, S.; Yang, J. H.; He, A. S.; Gu, B. L.

1995-02-01

A positron annihilation study of Y 1- xPr xBa 2Cu 3O 7 was performed. The results showed that charge transfer between the CuO 2 planes and 1D CuO chains upon Pr doping, as proposed in the literature, did not occur. Pr doping suppressed the anomaly of positron annihilation lifetime near and below Tc which has been observed in YBa 2Cu 3O 7. The perfection of the 1D CuO chains was reduced by Pr doping and this may be partly responsible for the increase of resistivity with Pr doping, and finally the semiconducting behaviour of DC resistivity in Y 1- xPr xBa 2Cu 3O 7 with x > 0.6.

When the science fails and the ethics works: 'Fail-safe' ethics in the FEM-PrEP study.

PubMed

Kingori, Patricia

2015-12-01

This paper will explore the concept of 'fail safe' ethics in the FEM PrEP trial, and the practice of research and ethics on the ground. FEM-PrEP examined the efficacy of PrEP in African women after promising outcomes in research conducted with MSM. This was a hugely optimistic time and FEM-PrEP was mobilised using rights-based ethical arguments that women should have access to PrEP. This paper will present data collected during an ethnographic study of frontline research workers involved in FEM-PrEP. During our discussions, 'fail-safe' ethics emerged as concept that encapsulated their confidence that their ethics could not fail. However, in 2011, FEM-PrEP was halted and deemed a failure. The women involved in the study were held responsible because contrary to researcher's expectations they were not taking the oral PrEP being researched. This examination of FEM-PrEP will show that ethical arguments are increasingly deployed to mobilise, maintain and in some cases stop trials in ways which, at times, are superseded or co-opted by other interests. While promoting the interests of women, rights-based approaches are argued to indirectly justify the continuation of individualised, biomedical interventions which have been problematic in other women-centred trials. In this examination of FEM-PrEP, the rights-based approach obscured: ethical concerns beyond access to PrEP; the complexities of power relationships between donor and host countries; the operations of the HIV industry in research-saturated areas and the cumulative effect of unfilled expectations in HIV research and how this has shaped ideas of research and ethics.

Moss Pathogenesis-Related-10 Protein Enhances Resistance to Pythium irregulare in Physcomitrella patens and Arabidopsis thaliana

PubMed Central

Castro, Alexandra; Vidal, Sabina; Ponce de León, Inés

2016-01-01

Plants respond to pathogen infection by activating signaling pathways leading to the accumulation of proteins with diverse roles in defense. Here, we addressed the functional role of PpPR-10, a pathogenesis-related (PR)-10 gene, of the moss Physcomitrella patens, in response to biotic stress. PpPR-10 belongs to a multigene family and encodes a protein twice the usual size of PR-10 proteins due to the presence of two Bet v1 domains. Moss PR-10 genes are differentially regulated during development and inoculation with the fungal pathogen Botrytis cinerea. Specifically, PpPR-10 transcript levels increase significantly by treatments with elicitors of Pectobacterium carotovorum subsp. carotovorum, spores of B. cinerea, and the defense hormone salicylic acid. To characterize the role of PpPR-10 in plant defense against pathogens, we conducted overexpression analysis in P. patens and in Arabidopsis thaliana. We demonstrate that constitutive expression of PpPR-10 in moss tissues increased resistance against the oomycete Pythium irregulare. PpPR-10 overexpressing moss plants developed less symptoms and decreased mycelium growth than wild type plants. In addition, PpPR-10 overexpressing plants constitutively produced cell wall depositions in protonemal tissue. Ectopic expression of PpPR-10 in Arabidopsis resulted in increased resistance against P. irregulare as well, evidenced by smaller lesions and less cellular damage compared to wild type plants. These results indicate that PpPR-10 is functionally active in the defense against the pathogen P. irregulare, in both P. patens and Arabidopsis, two evolutionary distant plants. Thus, P. patens can serve as an interesting source of genes to improve resistance against pathogen infection in flowering plants. PMID:27200053

Mechanism of Scrapie Prion Precipitation with Phosphotungstate Anions

PubMed Central

2015-01-01

The phosphotungstate anion (PTA) is widely used to facilitate the precipitation of disease-causing prion protein (PrPSc) from infected tissue for applications in structural studies and diagnostic approaches. However, the mechanism of this precipitation is not understood. In order to elucidate the nature of the PTA interaction with PrPSc under physiological conditions, solutions of PTA were characterized by NMR spectroscopy at varying pH. At neutral pH, the parent [PW12O40]3– ion decomposes to give a lacunary [PW11O39]7– (PW11) complex and a single orthotungstate anion [WO4]2– (WO4). To measure the efficacy of each component of PTA, increasing concentrations of PW11, WO4, and mixtures thereof were used to precipitate PrPSc from brain homogenates of scrapie prion-infected mice. The amount of PrPSc isolated, quantified by ELISA and immunoblotting, revealed that both PW11 and WO4 contribute to PrPSc precipitation. Incubation with sarkosyl, PTA, or individual components of PTA resulted in separation of higher-density PrP aggregates from the neuronal lipid monosialotetrahexosylganglioside (GM1), as observed by sucrose gradient centrifugation. These experiments revealed that yield and purity of PrPSc were greater with polyoxometalates (POMs), which substantially supported the separation of lipids from PrPSc in the samples. Interaction of POMs and sarkosyl with brain homogenates promoted the formation of fibrillar PrPSc aggregates prior to centrifugation, likely through the separation of lipids like GM1 from PrPSc. We propose that this separation of lipids from PrP is a major factor governing the facile precipitation of PrPSc by PTA from tissue and might be optimized further for the detection of prions. PMID:25695325

Fluoride-induced thyroid dysfunction in rats: roles of dietary protein and calcium level.

PubMed

Wang, H; Yang, Z; Zhou, B; Gao, H; Yan, X; Wang, J

2009-02-01

To assess the roles of dietary protein (Pr) and calcium (Ca) level associated with excessive fluoride (F) intake and the impact of dietary Pr, Ca, and F on thyroid function, 144 30-day-old Wistar albino rats were randomly allotted to six groups of 24 (female:male = 1:1). The six groups were fed (1) a normal control (NC) diet (17.92% Pr, 0.85% Ca = NC group); (2) the NC diet and high F (338 mg NaF [=150 mg F ion]/L in their drinking water = NC+F group); (3) low Pr and low Ca diet (10.01% Pr, 0.24% Ca = LPrLCa group); (4) low Pr and low Ca diet plus high F = LPrLCa+F group; (5) high Pr and low Ca diet plus high F (25.52% Pr, 0.25% Ca = HPrLCa+F group); and (6) low Pr and high Ca diet plus high F (10.60% Pr, 1.93% Ca = LPrHCa+F group). The areas of thyroid follicles were determined by Image-Proplus 5.1, and triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) levels in serum were measured by radioimmunoassay. The histopathological study revealed obviously flatted follicular epithelia cells and hyperplastic nodules, consisting of thyroid parafollicular cells that appeared by excessive F ingestion, on the 120th day. Pr or Ca supplementation reverses the F-induced damage in malnutrition. The serum T3, FT3, T4, and FT4 levels in the NC+F group were significantly decreased and significantly increased in the LPrLCa+F group. Thus, excessive F administration induces thyroid dysfunction in rats; dietary Pr and Ca level play key roles in F-induced thyroid dysfunction.

Salicylic acid-dependent and -independent impact of an RNA-binding protein on plant immunity.

PubMed

Hackmann, Christian; Korneli, Christin; Kutyniok, Magdalene; Köster, Tino; Wiedenlübbert, Matthias; Müller, Caroline; Staiger, Dorothee

2014-03-01

Plants overexpressing the RNA-binding protein AtGRP7 (AtGRP7-ox plants) constitutively express the PR-1 (PATHOGENESIS-RELATED-1), PR-2 and PR-5 transcripts associated with salicylic acid (SA)-mediated immunity and show enhanced resistance against Pseudomonas syringae pv. tomato (Pto) DC3000. Here, we investigated whether the function of AtGRP7 in plant immunity depends on SA. Endogenous SA was elevated fivefold in AtGRP7-ox plants. The elevated PR-1, PR-2 and PR-5 levels were eliminated upon expression of the salicylate hydroxylase nahG in AtGRP7-ox plants and elevated PR-1 levels were suppressed by sid (salicylic acid deficient) 2-1 that is impaired in SA biosynthesis. RNA immunoprecipitation showed that AtGRP7 does not bind the PR-1 transcript in vivo, whereas it binds PDF1.2. Constitutive or inducible AtGRP7 overexpression increases PR-1 promoter activity, indicating that AtGRP7 affects PR-1 transcription. In line with this, the effect of AtGRP7 on PR-1 is suppressed by npr (non-expressor of PR genes) 1. Whereas AtGRP7-ox plants restricted growth of Pto DC3000 compared with wild type (wt), sid2-1 AtGRP7-ox plants allowed more growth than AtGRP7-ox plants. Furthermore, we show an enhanced hypersensitive response triggered by avirulent Pto DC3000 (AvrRpt2) in AtGRP7-ox compared with wt. In sid2-1 AtGRP7-ox, an intermediate phenotype was observed. Thus, AtGRP7 has both SA-dependent and SA-independent effects on plant immunity. © 2013 John Wiley & Sons Ltd.

Acceptability and willingness to use HIV pre-exposure prophylaxis among HIV-negative men who have sex with men in Switzerland.

PubMed

Gredig, Daniel; Uggowitzer, Franziska; Hassler, Benedikt; Weber, Patrick; Nideröst, Sibylle

2016-01-01

Pre-exposure prophylaxis (PrEP) is discussed as an additional HIV prevention method targeting men who have sex with men (MSM). So far, PrEP has not been approved in Switzerland and only little is known about the acceptability of PrEP among MSM living in Switzerland. Given the slow uptake of PrEP among MSM in the USA, the objectives of the study were to investigate the acceptability for PrEP and to identify factors influencing the acceptability for this prevention method and the willingness to adopt it. During a 4-month period we conducted five focus group discussions with 23 consecutively sampled HIV-negative MSM aged 22-60 years living in Switzerland. We analyzed the data according to qualitative content analysis. The acceptability of PrEP varied considerably among the participants. Some would use PrEP immediately after its introduction in Switzerland because it provides an alternative to condoms which they are unable or unwilling to use. Others were more ambivalent towards PrEP but still considered it (1) an additional or alternative protection to regular condom use, (2) an option to engage in sexual activities with less worries and anxieties or (3) a protection during receptive anal intercourse independently of the sexual partner's protective behaviour. Some participants would not consider using PrEP at all: they do not see any benefit in PrEP as they have adopted safer sex practices and did not mention any problems with condom use. Others are still undecided and could imagine using an improved form of PrEP. The results provide a valuable basis for a model explaining the acceptability of PrEP among MSM and suggest including the personal HIV protection strategy in the considerations adopted.

Markedly Increased Susceptibility to Natural Sheep Scrapie of Transgenic Mice Expressing Ovine PrP

PubMed Central

Vilotte, Jean-Luc; Soulier, Solange; Essalmani, Rachid; Stinnakre, Marie-George; Vaiman, Daniel; Lepourry, Laurence; Da Silva, Jose Costa; Besnard, Nathalie; Dawson, Mike; Buschmann, Anne; Groschup, Martin; Petit, Stephanie; Madelaine, Marie-Francoise; Rakatobe, Sabine; Le Dur, Annick; Vilette, Didier; Laude, Hubert

2001-01-01

The susceptibility of sheep to scrapie is known to involve, as a major determinant, the nature of the prion protein (PrP) allele, with the VRQ allele conferring the highest susceptibility to the disease. Transgenic mice expressing in their brains three different ovine PrPVRQ-encoding transgenes under an endogenous PrP-deficient genetic background were established. Nine transgenic (tgOv) lines were selected and challenged with two scrapie field isolates derived from VRQ-homozygous affected sheep. All inoculated mice developed neurological signs associated with a transmissible spongiform encephalopathy (TSE) disease and accumulated a protease-resistant form of PrP (PrPres) in their brains. The incubation duration appeared to be inversely related to the PrP steady-state level in the brain, irrespective of the transgene construct. The survival time for animals from the line expressing the highest level of PrP was reduced by at least 1 year compared to those of two groups of conventional mice. With one isolate, the duration of incubation was as short as 2 months, which is comparable to that observed for the rodent TSE models with the briefest survival times. No survival time reduction was observed upon subpassaging of either isolate, suggesting no need for adaptation of the agent to its new host. Overexpression of the transgene was found not to be required for transmission to be accelerated compared to that observed with wild-type mice. Conversely, transgenic mice overexpressing murine PrP were found to be less susceptible than tgOv lines expressing ovine PrP at physiological levels. These data argue that ovine PrPVRQ provided a better substrate for sheep prion replication than did mouse PrP. Altogether, these tgOv mice could be an improved model for experimental studies on natural sheep scrapie. PMID:11390599

Azole Functionalized Polyoxo-Titanium Clusters with Sunlight-Driven Dye Degradation Applications: Synthesis, Structure, and Photocatalytic Studies.

PubMed

Narayanam, Nagaraju; Chintakrinda, Kalpana; Fang, Wei-Hui; Kang, Yao; Zhang, Lei; Zhang, Jian

2016-10-06

Six polyoxo-titanium clusters (PTCs) with varying nuclearities containing Ti-N bonds and heteronuclearity, namely, [Ti 6 (μ 3 -O) 2 (μ 2 -O) 2 (O 3 P-Phen) 2 (OiPr) 10 (1-hbta) 2 ] (PTC-37), Ti 8 (μ 3 -O) 2 (μ 2 -O) 2 (O 3 P-Phen) 2 (OiPr) 16 (adn) 2 (NO 3 ) 2 ] (PTC-38), [Ti 4 (μ 3 -O)(μ 2 -O)(μ 2 -OiPr) 2 (OiPr) 4 (O 3 P-Phen) 3 (1,10-phn)](HOiPr) (PTC-39), [Ti 4 (μ 3 -O)(μ 2 -OiPr) 3 (OiPr) 5 (O 3 P-Phen) 3 (Im)] (PTC-40), [Ti 4 (μ 3 -O)(μ 2 -OiPr) 3 (OiPr) 5 (O 3 P-Phen) 3 (Im)][Ti 3 M(μ 3 -O)(μ 2 -OiPr) 3 (OiPr) 3 (O 3 P-Phen) 3 (Im)] (M = Co for PTC-41 and M = Zn for PTC-42; O 3 P-Phen = phenyl phosphonate, 1-hbta = 1-hydroxy benzotriazolate, adn = adenine, 1,10-phn = 1,10-phenanthroline, Im = imidazolate, and OiPr = isopropoxide) were prepared as crystalline samples and structurally characterized. Simultaneous doping of nitrogen and transition metal heteroatoms into the Ti-O clusters created complex chemical environments in the resulting hybrid materials. Thus, photocatalytic methylene blue degradation studies were performed to understand structure-property relationships in these Ti cluster-based materials. The complex chemical environment created in these novel molecular clusters had proved to exhibit ligand-dependent photocatalytic activities under normal sunlight. Adenine-functionalized PTC-38 presented moderate activities, while other PTCs all show rapid dye degradation.

The effect of oral preexposure prophylaxis on the progression of HIV-1 seroconversion

PubMed Central

Donnell, Deborah; Ramos, Eric; Celum, Connie; Baeten, Jared; Dragavon, Joan; Tappero, Jordan; Lingappa, Jairam R.; Ronald, Allan; Fife, Kenneth; Coombs, Robert W.

2017-01-01

Objective: To investigate whether oral preexposure prophylaxis (PrEP) alters timing and patterns of seroconversion when PrEP use continues after HIV-1 infection. Design: Retrospective testing of the timing of Fiebig stage HIV-1 seroconversion in the Partners PrEP Study, a randomized placebo-controlled clinical trial of PrEP conducted in Kenya and Uganda. Methods: Specimens from 138 seroconverters were collected every 3 months and when HIV-1 infection was suspected based on monthly rapid HIV-1 tests. Progression of seroconversion was compared between randomized groups (PrEP versus placebo) and per-protocol groups (placebo versus PrEP participants with detectable tenofovir during the seroconversion period) using laboratory assessment of Fiebig stage. Delay in site-detection of seroconversion and association with PrEP drug-regimen resistant virus were assessed using logistic regression. Analysis of time to each Fiebig stage used maximum likelihood estimation with a parametric model to accommodate the varying lengths of HIV-infection intervals. Results: There was a significant increase in delayed site detection of infection associated with PrEP (odds ratio = 3.49, P = 0.044). Delay in detection was not associated with increased risk of resistance in the PrEP arm (odds ratio = 0.93, P = 0.95). Estimated time to each Fiebig stage was elongated in seroconverters with evidence of ongoing PrEP use, significantly for only Stage 5 (28 versus 17 days, P = 0.05). Adjusted for Fiebig stage, viral RNA was ∼2/3 log lower in those assigned to PrEP compared with placebo; no differences were found in Architect signal to cut-off at any stage. Conclusion: Ongoing PrEP use in seroconverters may delay detection of infection and elongate seroconversion, although the delay does not increase risk of resistance. PMID:28692542

Pre-exposure prophylaxis for HIV prevention in women: current perspectives

PubMed Central

Flash, Charlene A; Dale, Sannisha K; Krakower, Douglas S

2017-01-01

There are ~900,000 new HIV infections among women every year, representing nearly half of all new HIV infections globally. In the US, nearly one-fifth of all new HIV infections occur among women, and women from racial and ethnic minority communities experience disproportionately high rates of new HIV infections. Thus, there is a need to develop and implement effective HIV prevention strategies for women in the US and internationally, with a specific need to advance strategies in minority communities. Previous studies have demonstrated that oral HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral medications by HIV-uninfected persons to prevent HIV acquisition, can reduce HIV incidence among women who are adherent to PrEP. However, to date, awareness and uptake of PrEP among women have been very limited, suggesting a need for innovative strategies to increase the knowledge of and access to PrEP among women in diverse settings. This narrative review summarizes the efficacy and safety data of PrEP in women, discusses considerations related to medication adherence for women who use PrEP, and highlights behavioral, social, and structural barriers to maximize the effectiveness of PrEP in women. It also reviews novel modalities for PrEP in women which are being developed and tested, including topical formulations and long-acting injectable agents that may offer advantages as compared to oral PrEP and proposes a community-oriented, social networking framework to increase awareness of PrEP among women. If women are provided with access to PrEP and support to overcome social and structural barriers to adhere to PrEP, this prevention strategy holds great promise to impact the HIV epidemic among women in the US and globally. PMID:28615975

Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

PubMed

Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie; Liao, Donghua; Gregersen, Hans; Krogh, Klaus; Drewes, Asbjørn Mohr

2017-11-01

Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

PubMed

Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

2010-08-01

Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.

Acceptability of HIV Pre-Exposure Prophylaxis (PrEP) and Implementation Challenges Among Men Who Have Sex with Men in India: A Qualitative Investigation.

PubMed

Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Mengle, Shruta; Varghese, Jarvis; Nelson, Ruban; Bharat, Shalini

2015-10-01

This qualitative study explored the acceptability of HIV pre-exposure prophylaxis (PrEP) among MSM in India, and identified facilitators and barriers to future PrEP uptake. In 2014, we conducted 10 focus groups (n=61) among a purposive sample of diverse MSM recruited through community-based organizations in Chennai and Mumbai, and 10 key informant interviews with community leaders and health care providers. Participants' mean age was 26.1 years (SD 4.8); 62% completed secondary education, and 42% engaged in sex work. No focus group participants had heard of PrEP, but once explained, most reported they would likely use it. PrEP was alternately perceived as a 'back-up plan', a condom substitute, or a burden with concurrent condom use. Facilitators were potential for covert use, sex without condoms, and anxiety-less sex. Potential barriers emerged around stigma associated with PrEP use, fear of disclosures to one's family, wife, or male steady partner, and being labeled as HIV-positive or promiscuous by peers. Preferences emerged for intermittent rather than daily PrEP use, injectable PrEP, and free or subsidized access through community organizations or government hospitals. Key informants expressed additional concerns about risk compensation, non-adherence, and impact on ART availability for treatment. Demonstration projects are needed in India to support PrEP implementation tailored for at-risk MSM. Educational interventions for MSM should address concerns about PrEP effectiveness, side effects, and mitigate risk compensation. Community engagement may facilitate broad acceptability and challenge stigma around PrEP use. Importantly, provision of free or subsidized PrEP is necessary to making implementation feasible among low socioeconomic status MSM in India.

The effect of Houttuynia cordata injection on pseudorabies herpesvirus (PrV) infection in vitro.

PubMed

Ren, Xiaofeng; Sui, Xiuwen; Yin, Jiechao

2011-02-01

Pseudorabies herpesvirus (PrV) belongs to the Alphaherpesvirinae. Piglets infected with PrV die within a few days. Development of effective antiviral agents is one alternative or complementary method to prevent PrV infection. Houttuynia cordata Thunb. (Saururaceae), H. cordata, a traditional Chinese medicine, is often used to relieve lung abnormal symptoms, infectious disease, refractory hemoptysis and malignant pleural effusion in China. The present study aimed to investigate the effect of H. cordata injection on cell infection by PrV using Vero cells (a monkey kidney cell line) and swine testis cells (ST) as models. The infectivity of PrV was determined by plaque assays when H. cordata was applied to the virus, to the virus infected cells, and to the cells prior to infection. The genomic DNA copies post-drug treatment were confirmed by PCR and reverse transcription PCR. The cell apoptosis caused by the virus was analyzed. H. cordata efficiently inhibited cell infection after incubating the drug with PrV. Nevertheless, H. cordata was more efficient in Vero cells than in ST cells in terms of its inhibitory effect. Low-dosage drug inhibited cell apoptosis induced by PrV; nevertheless, high-dosage drug alone resulted in cell apoptosis. H. cordata has a direct inhibitory activity against PrV in vitro. H. cordata may be used as an anti-PrV agent or combined with other anti-PrV agents. PrV infection induces cell apoptosis and H. cordata inhibits cell infection. The optimal administration dosage of H. cordata should be taken into account in the future, because high-dosage H. cordata alone causes cell apoptosis.

Evaluating the impact of prioritization of antiretroviral pre-exposure prophylaxis (PrEP) in New York City

PubMed Central

Kessler, Jason; Myers, Julie E.; Nucifora, Kimberly A.; Mensah, Nana; Toohey, Christopher; Khademi, Amin; Cutler, Blayne; Braithwaite, R. Scott

2015-01-01

Objective To compare the value and effectiveness of different prioritization strategies of pre-exposure prophylaxis (PrEP) in New York City (NYC). Design Mathematical modeling utilized as clinical trial is not feasible. Methods Using a model accounting for both sexual and parenteral transmission of HIV we compare different prioritization strategies (PPS) for PrEP to two scenarios—no PrEP and PrEP for all susceptible at-risk individuals. The PPS included PrEP for all MSM, only high-risk MSM, high-risk heterosexuals, and injection drug users, and all combinations of these four strategies. Outcomes included HIV infections averted, and incremental cost effectiveness (per-infection averted) ratios. Initial assumptions regarding PrEP included a 44% reduction in HIV transmission, 50% uptake in the prioritized population and an annual cost per person of $9,762. Sensitivity analyses on key parameters were conducted. Results Prioritization to all MSM results in a 19% reduction in new HIV infections. Compared to PrEP for all persons at-risk this PPS retains 79% of the preventative effect at 15% of the total cost. PrEP prioritized to only high-risk MSM results in a reduction in new HIV infections of 15%. This PPS retains 60% of the preventative effect at 6% of the total cost. There are diminishing returns when PrEP utilization is expanded beyond this group. Conclusions PrEP implementation is relatively cost-inefficient under our initial assumptions. Our results suggest that PrEP should first be promoted among MSM who are at particularly high-risk of HIV acquisition. Further expansion beyond this group may be cost-effective, but is unlikely to be cost-saving. PMID:25493594

Three-dimensional fusion of spaceborne and ground radar reflectivity data using a neural network-based approach

NASA Astrophysics Data System (ADS)

Kou, Leilei; Wang, Zhuihui; Xu, Fen

2018-03-01

The spaceborne precipitation radar onboard the Tropical Rainfall Measuring Mission satellite (TRMM PR) can provide good measurement of the vertical structure of reflectivity, while ground radar (GR) has a relatively high horizontal resolution and greater sensitivity. Fusion of TRMM PR and GR reflectivity data may maximize the advantages from both instruments. In this paper, TRMM PR and GR reflectivity data are fused using a neural network (NN)-based approach. The main steps included are: quality control of TRMM PR and GR reflectivity data; spatiotemporal matchup; GR calibration bias correction; conversion of TRMM PR data from Ku to S band; fusion of TRMM PR and GR reflectivity data with an NN method; interpolation of reflectivity data that are below PR's sensitivity; blind areas compensation with a distance weighting-based merging approach; combination of three types of data: data with the NN method, data below PR's sensitivity and data within compensated blind areas. During the NN fusion step, the TRMM PR data are taken as targets of the training NNs, and gridded GR data after horizontal downsampling at different heights are used as the input. The trained NNs are then used to obtain 3D high-resolution reflectivity from the original GR gridded data. After 3D fusion of the TRMM PR and GR reflectivity data, a more complete and finer-scale 3D radar reflectivity dataset incorporating characteristics from both the TRMM PR and GR observations can be obtained. The fused reflectivity data are evaluated based on a convective precipitation event through comparison with the high resolution TRMM PR and GR data with an interpolation algorithm.

A PR-4 gene identified from Malus domestica is involved in the defense responses against Botryosphaeria dothidea.

PubMed

Bai, Suhua; Dong, Chaohua; Li, Baohua; Dai, Hongyi

2013-01-01

Pathogenesis-related protein-4 (PR-4) family is a group of proteins with a Barwin domain in C-terminus and generally thought to be involved in plant defense responses. However, their detailed roles are poorly understood in defense of apple plant against pathogenic infection. In the present study, a new PR-4 gene (designated as MdPR-4) was identified from Malus domestica, and its roles in defense responses of apple were investigated. The open reading frame of MdPR-4 gene is of 447 bp encoding a protein of 148 amino acids with a Barwin domain in C-terminus and a signal peptide of 26 amino acids in N-terminus. Sequence and structural analysis indicated that MdPR-4 protein belongs to class II of PR-4 family. The high-level expression of MdPR-4 was observed in flowers and leaves as revealed by quantitative real time PCR. The temporal expression analysis demonstrated that MdPR-4 expression could be up-regulated by Botryosphaeria dothidea infection and salicylic acid (SA) or methyl jasmonate (MeJA) treatment, but suppressed by diethyldithiocarbamic acid (DIECA). In vitro assays, recombinant MdPR-4 protein exhibited ribonuclease activity specific for single strand RNA and significant inhibition to hyphal growth of three apple pathogenic fungi B. dothidea, Valsa ceratosperma and Glomerella cingulata. Moreover, the inhibition was reduced by the presence of 5'-ADP. Taken all together, the results indicate that MdPR-4 protein is involved in the defense responses of apple against pathogenic attack by directly inhibiting hyphal growth, and the inhibition is correlated with its ribonuclease activity, where as MdPR-4 expression is regulated by both SA and JA signaling pathway. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Adherence to Preexposure Prophylaxis: Current, Emerging, and Anticipated Bases of Evidence

PubMed Central

Amico, K. Rivet; Stirratt, Michael J.

2014-01-01

Despite considerable discussion and debate about adherence to preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV), scant data are available that characterize patterns of adherence to open-label PrEP. The current evidence base is instead dominated by research on adherence to placebo-controlled investigational drug by way of drug detection in active-arm participants of large randomized controlled trials (RCTs). Important differences between the context of blinded RCTs and open-label use suggest caution when generalizing from study product adherence to real-world PrEP use. Evidence specific to open-label PrEP adherence is presently sparse but will expand rapidly over the next few years as roll-out, demonstration projects, and more rigorous research collect and present findings. The current evidence bases established cannot yet predict uptake, adherence, or persistence with open-label effective PrEP. Emerging evidence suggests that some cohorts could execute better adherence in open-label use vs placebo-controlled research. Uptake of PrEP is presently slow in the United States; whether this changes as grassroots and community efforts increase awareness of PrEP as an effective HIV prevention option remains to be determined. As recommended by multiple guidelines for PrEP use, all current demonstration projects offer PrEP education and/or counseling. PrEP support approaches generally fall into community-based, technology, monitoring, and integrated sexual health promotion approaches. Developing and implementing research that moves beyond simple correlates of either study product use or open-label PrEP adherence toward more comprehensive models of sociobehavioral and socioecological adherence determinants would greatly accelerate progress. Intervention research is needed to identify effective models of support for open-label PrEP adherence. PMID:24926036

Alzheimer's amyloid-β oligomers rescue cellular prion protein induced tau reduction via the Fyn pathway.

PubMed

Chen, Rong-Jie; Chang, Wei-Wei; Lin, Yu-Chun; Cheng, Pei-Lin; Chen, Yun-Ru

2013-09-18

Amyloid-β (Aβ) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aβ oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aβ oligomers have been shown to specifically interact with cellular prion protein (PrP(C)) where the role of PrP(C) in AD is still not fully understood. To investigate the downstream mechanism of PrP(C) and Aβ oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP(C) and studied the effect under Aβ oligomer treatment. By Western blotting, we found that PrP(C) overexpression down-regulated tau protein and Aβ oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP(C), the high AD risk polymorphic allele in human prion gene. PrP(C) lacking the Aβ oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP(C) effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP(C)-induced tau reduction and Aβ oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aβ-PrP(C)-tau signaling. Overall, our results demonstrated that PrP(C) down-regulated tau via the Fyn pathway and the effect can be regulated by Aβ oligomers. Our study facilitated the understanding of molecular mechanisms among PrP(C), tau, and Aβ oligomers.

A Tale of Two Fleets: A Russian Perspective on the 1973 Naval Standoff in the Mediterranean

DTIC Science & Technology

2004-01-01

destroyers Reshitel’nyi (Kashin class/pr. 61) and Nakhodchivyi ( Kotlin class/pr. 56) out of Varna, Bulgaria, where they had helped commemorate Bul...cruiser Mikhail Kutuzov [Sverdlov class/pr. 68-A]), three SAM destroyers (Bravyi [converted Kotlin class], Bedovyi, Boikii [Krupnyi class/pr. 57bis... Kotlin class], Sereznyi, and Sovershennyi [both Skoryi class/pr. 30bis]), six escort vessels, six SSGs (conventionally powered cruise-missile submarines

Execution Time of Symmetric Eigensolvers

DTIC Science & Technology

1997-01-01

322 , 398,405 nP n0=1;nb (2n 0 nb pr +dlog2(pr)em nbpc +3 +2m nb 2 2 pc 3+2 vnbn0 nb pr 3 +2nn 0 nb p 3) n2 pr + nm pc dlog2(pr)e + n nb 3+ nm...Sci. Comput., pages 1331{1348, 1994. http://www.nws.e-technik. tu-muenchen.de/~ jugo /pub/SIAMjac.ps.Z. [86] A. Greenbaum and J. Dongarra. Experiments

Prion protein functions as a ferrireductase partner for ZIP14 and DMT1

PubMed Central

Qian, Juan; Beserra, Amber; Suda, Srinivas; Singh, Ajay; Hopfer, Ulrich; Chen, Shu G.; Garrick, Michael D.; Turner, Jerrold R.; Knutson, Mitchell D.; Singh, Neena

2015-01-01

Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI) and transferrin (Tf)-iron at the plasma membrane and endosomes respectively by ferrireductase (FR) proteins for transport across biological membranes through divalent metal transporters. Here, we report that prion-protein (PrPC), a ubiquitously expressed glycoprotein most abundant on neuronal cells, functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14. Thus, absence of PrPC in PrP-knock-out (PrP−/−) mice resulted in markedly reduced liver iron stores, a deficiency that was not corrected by chronic or acute administration of iron by the oral or intra-peritoneal routes. Likewise, preferential radiolabeling of circulating NTBI with 59Fe revealed significantly reduced uptake and storage of NTBI by the liver of PrP−/− mice relative to matched PrP+/+ controls. However, uptake, storage, and utilization of ferritin-bound iron that does not require reduction for uptake was increased in PrP−/− mice, indicating a compensatory response to the iron-deficiency. Expression of exogenous PrPC in HepG2-cells increased uptake and storage of ferric-iron (Fe3+), not ferrous-iron (Fe2+) from the medium, supporting the function of PrPC as a plasma membrane FR. Co-expression of PrPC with ZIP14 and DMT1 in HepG2 cells increased uptake of Fe3+ significantly, and surprisingly, increased the ratio of N-terminally truncated PrPC forms lacking the FR domain relative to full-length PrPC. Together, these observations indicate that PrPC promotes, and possibly regulates the uptake of NTBI through DMT1 and Zip14 via its FR activity. Implications of these observations for neuronal iron homeostasis under physiological and pathological conditions are discussed. PMID:25862412

Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice

PubMed Central

Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg

2017-01-01

Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1–4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain. PMID:29220360

[Regulatory effect and mechanism of RNA binding motif protein 38 on the expression of progesterone receptor in human breast cancer ZR-75-1 cells].

PubMed

Lou, P P; Li, C L; Xia, T S; Shi, L; Wu, J; Zhou, X J; Wang, Y; Ding, Q

2016-06-23

To investigate the regulatory mechanism of RNA binding motif protein 38 (RNPC1) on the expression of progesterone receptor (PR) in breast cancer cell line ZR-75-1. Lentiviral vector was used to induce overexpression of RNPC1 in ZR-75-1 cells. qRT-PCR and Western blot were used to assess the regulatory effect of RNPC1 on PR expression. Actinomycin was used to detect the regulatory mechanism involved. Immunohistochemical (IHC) staining was used to determine the protein expression of RNPC1 and PR in 80 breast cancer tissues. IHC staining showed that the expression of RNPC1 was significantly higher in the PR positive breast cancer tissues than that in the PR negative breast cancer tissues (P<0.05). The qRT-PCR results showed that overexpression of RNPC1 in ZR-75-1 cells significantly upregulated the mRNA level of PR (1.764±0.028 vs. 1.001±0.037, P<0.01), whereas knockdown of RNPC1 did the opposite (0.579± 0.007 vs. 1.000±0.002, P<0.01). The Western blot results also showed that overexpression of RNPC1 up-regulated PR levels, while knockdown of RNPC1 resulted in down-regulation of PR levels in the ZR-75-1 cells.The actinomycin assay showed that overexpression of RNPC1 increased the mRNA stability of PR. The half-life of PR mRNA was increased from 4.0 h to 6.5 h. Knockdown of RNPC1 decreased the mRNA stability of PR and the half-life of PR transcript was decreased from 4.1 h to 3.0 h. RNPC1 plays a crucial role in regulating the expression of PR in breast cancer ZR-75-1 cells.

HIV Pre-Exposure Prophylaxis Interest among Female Sex Workers in Guangxi, China

PubMed Central

Zou, Yunfeng; Yang, Xiaobo; Abdullah, Abu S.; Zhong, Xiaoni; Ruan, Yuhua; Lin, Xinqin; Li, Mingqiang; Wu, Deren; Jiang, Junjun; Xie, Peiyan; Huang, Jiegang; Liang, Bingyu; Zhou, Bo; Su, Jinming; Liang, Hao; Huang, Ailong

2014-01-01

Objectives Acceptability of pre-exposure prophylaxis (PrEP) and willingness to participate in a clinical trial for both safety and efficacy of PrEP were investigated among female sex workers (FSWs) in Guangxi, China. Methods A cross-sectional study was performed in three cities in Guangxi. Structured, self-administered questionnaires were used to assess the acceptability of PrEP and the willingness to participate in a clinical trial. Multivariable logistic regression models were fitted to identify predictors. Results Among 405 participants, 15.1% had heard of PrEP. If PrEP was deemed to be effective, safe and provided for free, 85.9% reported that they would accept it, and 54.3% of those who accepted PrEP said that they would participate in a clinical trial. The increased acceptability of PrEP was associated with working in male dominated venues, higher income, a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, not being forced to use condoms by the gatekeepers, consistent use of condoms, and use of drugs to prevent STD infection. The increased willingness to participate in a clinical trial was associated with a poor family relationship, better HIV/AIDS knowledge, not realizing HIV risk from unfamiliar clients, a willingness to adhere to daily PreP use, and not being concerned about discrimination by others. The main reason for rejecting PrEP or participating in a clinical trial was the concern about the side effects of PrEP. Conclusions Acceptability of PrEP among Guangxi FSWs is relatively high, indicating that PrEP intervention programs may be feasible for Chinese FSWs. Given the fact that most of the participants had never heard of PrEP before, and that family, gatekeepers, and social discrimination could significantly affect its acceptability, a comprehensive mix of multiple interventions is necessary for the successful implementation of a PrEP program among this population in Guangxi. PMID:24465956

Pepper pathogenesis-related protein 4c is a plasma membrane-localized cysteine protease inhibitor that is required for plant cell death and defense signaling.

PubMed

Kim, Nak Hyun; Hwang, Byung Kook

2015-01-01

Xanthomonas campestris pv. vesicatoria (Xcv) type III effector AvrBsT triggers programmed cell death (PCD) and activates the hypersensitive response (HR) in plants. Here, we isolated and identified the plasma membrane localized pathogenesis-related (PR) protein 4c gene (CaPR4c) from pepper (Capsicum annuum) leaves undergoing AvrBsT-triggered HR cell death. CaPR4c encodes a protein with a signal peptide and a Barwin domain. Recombinant CaPR4c protein expressed in Escherichia coli exhibited cysteine protease-inhibitor activity and ribonuclease (RNase) activity. Subcellular localization analyses revealed that CaPR4c localized to the plasma membrane in plant cells. CaPR4c expression was rapidly and specifically induced by avirulent Xcv (avrBsT) infection. Transient expression of CaPR4c caused HR cell death in pepper leaves, which was accompanied by enhanced accumulation of H2 O2 and significant induction of some defense-response genes. Deletion of the signal peptide from CaPR4c abolished the induction of HR cell death, indicating a requirement for plasma membrane localization of CaPR4c for HR cell death. CaPR4c silencing in pepper disrupted both basal and AvrBsT-triggered resistance responses, and enabled Xcv proliferation in infected leaves. H2 O2 accumulation, cell-death induction, and defense-response gene expression were distinctly reduced in CaPR4c-silenced pepper. CaPR4c overexpression in transgenic Arabidopsis plants conferred greater resistance against infection by Pseudomonas syringae pv. tomato and Hyaloperonospora arabidopsidis. These results collectively suggest that CaPR4c plays an important role in plant cell death and defense signaling. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Falls among the elderly: risk factors in a population-based study.

PubMed

Rodrigues, Iara Guimarães; Fraga, Gustavo Pereira; Barros, Marilisa Berti de Azevedo

2014-01-01

The aim of the present study was to identify factors associated with the occurrence of falls among elderly adults in a population-based study (ISACamp 2008). A population-based cross-sectional study was carried out with two-stage cluster sampling. The sample was composed of 1,520 elderly adults living in the urban area of the city of Campinas, São Paulo, Brazil. The occurrence of falls was analyzed based on reports of the main accident occurred in the previous 12 months. Data on socioeconomic/demographic factors and adverse health conditions were tested for possible associations with the outcome. Prevalence ratios (PR) were estimated and adjusted for gender and age using the Poisson multiple regression analysis. Falls were more frequent, after adjustment for gender and age, among female elderly participants (PR = 2.39; 95% confidence interval (95% CI) 1.47 - 3.87), elderly adults (80 years old and older) (PR = 2.50; 95% CI 1.61 - 3.88), widowed (PR = 1.74; 95% CI 1.04 - 2.89) and among elderly adults who had rheumatism/arthritis/arthrosis (PR = 1.58; 95% CI 1.00 - 2.48), osteoporosis (PR = 1.71; 95% CI 1.18 - 2.49), asthma/bronchitis/emphysema (PR = 1,73; 95% CI 1.09 - 2.74), headache (PR = 1.59; 95% CI 1.07 - 2.38), mental common disorder (PR = 1.72; 95% CI 1.12 - 2.64), dizziness (PR = 2.82; 95% CI 1.98 - 4.02), insomnia (PR = 1.75; 95% CI 1.16 - 2.65), use of multiple medications (five or more) (PR = 2.50; 95% CI 1.12 - 5.56) and use of cane/walker (PR = 2.16; 95% CI 1.19 - 3,93). The present study shows segments of the elderly population who are more prone to falls through the identification of factors associated with this outcome. The findings can contribute to the planning of public health policies and programs addressed to the prevention of falls.

United States family planning providers' knowledge of and attitudes towards preexposure prophylaxis for HIV prevention: a national survey.

PubMed

Seidman, Dominika; Carlson, Kimberly; Weber, Shannon; Witt, Jacki; Kelly, Patricia J

2016-05-01

The Centers for Disease Control and Prevention defines HIV prevention as a core family planning service. The HIV community identified family planning visits as key encounters for women to access preexposure prophylaxis (PrEP) for HIV prevention. No studies explore US family planning providers' knowledge of and attitudes towards PrEP. We conducted a national survey of clinicians to understand barriers and facilitators to PrEP implementation in family planning. Family planning providers recruited via website postings, national meetings, and email completed an anonymous survey in 2015. Descriptive statistics were performed. Among 604 respondents, 495 were eligible for analysis and 342 were potential PrEP prescribers (physicians, nurse practitioners, midwives or physicians assistants). Among potential prescribers, 38% correctly defined PrEP [95% confidence interval (CI): 32.5-42.8], 37% correctly stated the efficacy of PrEP (95% CI: 32.0-42.4), and 36% chose the correct HIV test after a recent exposure (95% CI: 30.6-40.8). Characteristics of those who answered knowledge questions correctly included age less than 35 years, practicing in the Northeast or West, routinely offering HIV testing, providing rectal sexually transmitted infection screening or having seen any PrEP guidelines. Even among providers in the Northeast and West, the proportion of respondents answering questions correctly was less than 50%. Thirty-six percent of respondents had seen any PrEP guidelines. Providers identified lack of training as the main barrier to PrEP implementation; 87% wanted PrEP education. To offer comprehensive HIV prevention services, family planning providers urgently need training on PrEP and HIV testing. US family planning providers have limited knowledge about HIV PrEP and HIV testing, and report lack of provider training as the main barrier to PrEP provision. Provider education is needed to ensure that family planning clients access comprehensive HIV prevention methods. Copyright © 2016 Elsevier Inc. All rights reserved.

The pathogenesis-related protein PR-4b from Theobroma cacao presents RNase activity, Ca(2+) and Mg(2+) dependent-DNase activity and antifungal action on Moniliophthora perniciosa.

PubMed

Pereira Menezes, Sara; de Andrade Silva, Edson Mario; Matos Lima, Eline; Oliveira de Sousa, Aurizângela; Silva Andrade, Bruno; Santos Lima Lemos, Livia; Peres Gramacho, Karina; da Silva Gesteira, Abelmon; Pirovani, Carlos Priminho; Micheli, Fabienne

2014-06-11

The production and accumulation of pathogenesis-related proteins (PR proteins) in plants in response to biotic or abiotic stresses is well known and is considered as a crucial mechanism for plant defense. A pathogenesis-related protein 4 cDNA was identified from a cacao-Moniliophthora perniciosa interaction cDNA library and named TcPR-4b. TcPR-4b presents a Barwin domain with six conserved cysteine residues, but lacks the chitin-binding site. Molecular modeling of TcPR-4b confirmed the importance of the cysteine residues to maintain the protein structure, and of several conserved amino acids for the catalytic activity. In the cacao genome, TcPR-4b belonged to a small multigene family organized mainly on chromosome 5. TcPR-4b RT-qPCR analysis in resistant and susceptible cacao plants infected by M. perniciosa showed an increase of expression at 48 hours after infection (hai) in both cacao genotypes. After the initial stage (24-72 hai), the TcPR-4b expression was observed at all times in the resistant genotypes, while in the susceptible one the expression was concentrated at the final stages of infection (45-90 days after infection). The recombinant TcPR-4b protein showed RNase, and bivalent ions dependent-DNase activity, but no chitinase activity. Moreover, TcPR-4b presented antifungal action against M. perniciosa, and the reduction of M. perniciosa survival was related to ROS production in fungal hyphae. To our knowledge, this is the first report of a PR-4 showing simultaneously RNase, DNase and antifungal properties, but no chitinase activity. Moreover, we showed that the antifungal activity of TcPR-4b is directly related to RNase function. In cacao, TcPR-4b nuclease activities may be related to the establishment and maintenance of resistance, and to the PCD mechanism, in resistant and susceptible cacao genotypes, respectively.

TRMM Precipitation Radar Reflectivity Profiles Compared to High-Resolution Airborne and Ground-Based Radar Measurements

NASA Technical Reports Server (NTRS)

Heymsfield, G. M.; Geerts, B.; Tian, L.

1999-01-01

In this paper, TRMM (Tropical Rainfall Measuring Mission Satellite) Precipitation Radar (PR) products are evaluated by means of simultaneous comparisons with data from the high-altitude ER-2 Doppler Radar (EDOP), as well as ground-based radars. The comparison is aimed primarily at the vertical reflectivity structure, which is of key importance in TRMM rain type classification and latent heating estimation. The radars used in this study have considerably different viewing geometries and resolutions, demanding non-trivial mapping procedures in common earth-relative coordinates. Mapped vertical cross sections and mean profiles of reflectivity from the PR, EDOP, and ground-based radars are compared for six cases. These cases cover a stratiform frontal rainband, convective cells of various sizes and stages, and a hurricane. For precipitating systems that are large relative to the PR footprint size, PR reflectivity profiles compare very well to high-resolution measurements thresholded to the PR minimum reflectivity, and derived variables such as bright band height and rain types are accurate, even at high PR incidence angles. It was found that for, the PR reflectivity of convective cells small relative to the PR footprint is weaker than in reality. Some of these differences can be explained by non-uniform beam filling. For other cases where strong reflectivity gradients occur within a PR footprint, the reflectivity distribution is spread out due to filtering by the PR antenna illumination pattern. In these cases, rain type classification may err and be biased towards the stratiform type, and the average reflectivity tends to be underestimated. The limited sensitivity of the PR implies that the upper regions of precipitation systems remain undetected and that the PR storm top height estimate is unreliable, usually underestimating the actual storm top height. This applies to all cases but the discrepancy is larger for smaller cells where limited sensitivity is compounded by incomplete beam filling. Users of level three TRMM PR products should be aware of this scale dependency.

Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer

PubMed Central

Dai, Donghai; Meng, Xiangbing; Thiel, Kristina W.; Leslie, Kimberly K.; Yang, Shujie

2016-01-01

Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR). However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term “molecularly enhanced progestin therapy.” What remained unclear was the mechanism of action and if estrogen receptor α (ERα), the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERα at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi) was sufficient to restore functional PR expression, even in cells devoid of ERα. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data reveal a previously unanticipated inverse relationship between the tumor suppressor PR and the oncogene Myc in endometrial cancer. PMID:26859414

Preexposure prophylaxis-related stigma: strategies to improve uptake and adherence - a narrative review.

PubMed

Haire, Bridget G

2015-01-01

Despite high levels of efficacy, the implementation of preexposure prophylaxis (PrEP) as a strategy to prevent new HIV infection has been slow. Studies show that PrEP works so long as it is taken, making adherence one of the great challenges of effective PrEP implementation alongside issues of access and uptake. Given that effective PrEP use requires ongoing self-administration of pills by people at high risk of HIV acquisition, it is a strategy best understood not as simply biomedical, but as biobehavioral or biopsychosocial, meaning that that social, psychological, cultural, and structural factors all contribute to the success or failure of the intervention. The willingness of people at risk of HIV to take up and adhere to PrEP depends greatly upon social understandings - whether it is seen as effective, as a healthy option, and a socially acceptable strategy for preventing HIV. Stigma - unfavorable associations - can negatively influence the implementation of PrEP. Because it is associated with high-risk sexual activity, PrEP risks multiple stigmas that can differ according to specific cultural conditions. This includes the stigma of being related to HIV (which may also relate to other stigmas, such as homosexuality, sex work, and/or drug use) and the stigma of PrEP being an alternative to condoms (as condom use is associated with responsible sexual activity). PrEP-related stigma has emerged as a significant social harm that can arise from PrEP research participation, reported by trial participants from a range of different trial sites, different trial populations, and spanning different continents. Social marketing needs to redress PrEP-related stigmas through health promotion campaigns aimed at clinicians, HIV-affected communities, and people at high risk of HIV who might benefit from PrEP access. PrEP access needs to be reframed as a positive and responsible option to help people remain HIV-negative.

Implementation and Operational Research: A Cost-Effective, Clinically Actionable Strategy for Targeting HIV Preexposure Prophylaxis to High-Risk Men Who Have Sex With Men.

PubMed

Ross, Eric L; Cinti, Sandro K; Hutton, David W

2016-07-01

Preexposure prophylaxis (PrEP) is effective at preventing HIV infection among men who have sex with men (MSM), but there is uncertainty about how to identify high-risk MSM who should receive PrEP. We used a mathematical model to assess the cost-effectiveness of using the HIV Incidence Risk Index for MSM (HIRI-MSM) questionnaire to target PrEP to high-risk MSM. We simulated strategies of no PrEP, PrEP available to all MSM, and eligibility thresholds set to HIRI-MSM scores between 5 and 45, in increments of 5 (where a higher score predicts greater HIV risk). Based on the iPrEx, IPERGAY, and PROUD trials, we evaluated PrEP efficacies from 44% to 86% and annual costs from $5900 to 8700. We designate strategies with incremental cost-effectiveness ratio (ICER) ≤$100,000/quality-adjusted life-year (QALY) as "cost-effective." Over 20 years, making PrEP available to all MSM is projected to prevent 33.5% of new HIV infections, with an ICER of $1,474,000/QALY. Increasing the HIRI-MSM score threshold reduces the prevented infections, but improves cost-effectiveness. A threshold score of 25 is projected to be optimal (most QALYs gained while still being cost-effective) over a wide range of realistic PrEP efficacies and costs. At low cost and high efficacy (IPERGAY), thresholds of 15 or 20 are optimal across a range of other input assumptions; at high cost and low efficacy (iPrEx), 25 or 30 are generally optimal. The HIRI-MSM provides a clinically actionable means of guiding PrEP use. Using a score of 25 to determine PrEP eligibility could facilitate cost-effective use of PrEP among high-risk MSM who will benefit from it most.

PrP{sup C} displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrP{sup C} knockout mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertuchi, Fernanda R.; Bourgeon, Dominique M.G.; Landemberger, Michele C.

2012-02-03

Highlights: Black-Right-Pointing-Pointer PrP{sup C} in solution acts as a radical scavenger. Black-Right-Pointing-Pointer PrP{sup C} reduces hydrogen peroxide toxicity in astrocytes. Black-Right-Pointing-Pointer Increase in ROS disrupted the cell cycle in the PrP{sup C}-knockout astrocytes. Black-Right-Pointing-Pointer PrP{sup C} prevents the cell death independently of an SOD-like activity. -- Abstract: The PrP{sup C} protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP{sup C} in solution and its participation as a cell protector in astrocytes that weremore » subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP{sup C} decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu{sup 2+}/ascorbate/H{sub 2}O{sub 2}), which was demonstrated by approximately 70% less DMPO/OH{sup {center_dot}}. In cultured PrP{sup C}-knockout astrocytes from mice, the absence of PrP{sup C} caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H{sub 2}O{sub 2} treatment. This rapid increase in ROS disrupted the cell cycle in the PrP{sup C}-knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP{sup C} in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.« less

The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection.

PubMed

Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna

2017-05-01

People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

Semiautomated cell-free conversion of prion protein: applications for high-throughput screening of potential antiprion drugs.

PubMed

Breydo, Leonid; Bocharova, Olga V; Baskakov, Ilia V

2005-04-01

Transmissible spongiform encephalitis (TSE) is a lethal illness with no known treatment. Conversion of the cellular prion protein (PrP(C)) into the infectious isoform (PrP(Sc)) is believed to be the central event in the development of this disease. Recombinant PrP (rPrP) protein folded into the amyloid conformation was shown to cause the transmissible form of prion disease in transgenic mice and can be used as a surrogate model for PrP(Sc). Here, we introduced a semiautomated assay of in vitro conversion of rPrP protein to the amyloid conformation. We have examined the effect of known inhibitors of prion propagation on this conversion and found good correlation between their activity in this assay and that in other in vitro assays. We thus propose that the conversion of rPrP to the amyloid isoform can serve as a high-throughput screen for possible inhibitors of PrP(Sc) formation and potential anti-TSE drugs.

Evaluation of critical distances for energy transfer between Pr{sup 3+} and Ce{sup 3+} in yttrium aluminium garnet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, Peng; Wei, Xiantao; Yin, Min

A series of Pr{sup 3+}/Ce{sup 3+} doped yttrium aluminium garnet (Y{sub 3}Al{sub 5}O{sub 12} or simply YAG) phosphors were synthesized to investigate the energy transfer between Pr{sup 3+} and Ce{sup 3+} for their potential application in a white light-emitting diode and quantum information storage and processing. The excitation and emission spectra of YAG:Pr{sup 3+}/Ce{sup 3+} were measured and analyzed, and it revealed that the reabsorption between Pr{sup 3+} and Ce{sup 3+} was so weak that it can be ignored, and the energy transfer from Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{submore » 2}) did occur. By analyzing the excitation and the emission spectra, the energy transfer from Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{sub 2}) was examined in detail with an original strategy deduced from fluorescence dynamics and the Dexter energy transfer theory, and the critical distances of energy transfer were derived to be 7.9 Å and 4.0 Å for Pr{sup 3+} (5d) to Ce{sup 3+} (5d) and Ce{sup 3+} (5d) to Pr{sup 3+} ({sup 1}D{sub 2}), respectively. The energy transfer rates of the two processes of various concentrations were discussed and evaluated. Furthermore, for the purpose of sensing a single Pr{sup 3+} state with a Ce{sup 3+} ion, the optimal distance of Ce{sup 3+} from Pr{sup 3+} was evaluated as 5.60 Å, where the probability of success reaches its maximum value of 78.66%, and meanwhile the probabilities were evaluated for a series of Y{sup 3+} sites in a YAG lattice. These results will be of valuable reference for achievement of the optimal energy transfer efficiency in Pr{sup 3+}/Ce{sup 3+} doped YAG and other similar systems.« less

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection

PubMed Central

Di Biagio, Antonio; Signori, Alessio; Maserati, Renato; Nozza, Silvia; Gori, Andrea; Bonora, Stefano; Borderi, Marco; Ripamonti, Diego; Rossi, Maria Cristina; Orofino, Giancarlo; Quirino, Tiziana; Nunnari, Giuseppe; Celesia, Benedetto Maurizio; Martini, Salvatore; Sagnelli, Caterina; Mazzola, Giovanni; Colletti, Pietro; Bartolozzi, Dario; Bini, Teresa; Ladisa, Nicoletta; Castelnuovo, Filippo; Saracino, Annalisa; Lo Caputo, Sergio

2017-01-01

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice. PMID:28727818

Perceived HIV risk, actual sexual HIV risk and willingness to take pre-exposure prophylaxis among men who have sex with men in Toronto, Canada.

PubMed

Kesler, Maya A; Kaul, Rupert; Myers, Ted; Liu, Juan; Loutfy, Mona; Remis, Robert S; Gesink, Dionne

2016-11-01

Pre-exposure prophylaxis (PrEP) reduces HIV acquisition. Our goal was to determine the willingness of men who have sex with men (MSM) to take PrEP given perceived and actual HIV risk. HIV-negative MSM were recruited from September 2010 to June 2012 and asked about PrEP willingness and perceived HIV risk. Actual sexual HIV risk was measured by three condom-use components generated through principal components analysis. General HIV risk was measured using the HIV Incidence Risk Index for MSM (HIRI-MSM). Model 1 measured PrEP willingness given perceived and actual sexual HIV risk. Model 2 included actual HIV sexual risk, perceived HIV risk and general HIV risk. Model 3 removed actual sexual HIV risk. We recruited 150 HIV-negative MSM. About 55% were willing to take PrEP. Reasons for PrEP unwillingness were: low perceived risk (64%), side-effect concerns (44%), daily pill burden (16%) and efficacy concerns (4%). Model 1: MSM with high compared to low actual sexual HIV risk were more willing to use PrEP (OR 27.11, 95% CI 1.33-554.43) after adjusting for perceived risk, which was not significantly associated with PrEP willingness (OR 4.79, 95% CI 0.72-31.96). Model 2: MSM with high compared to low actual sexual HIV risk were more willing to use PrEP (OR 29.85, 95% CI 1.39-640.53) after adjusting for perceived and general HIV risk, neither of which was significantly associated with PrEP willingness (OR 5.07, 95% CI 0.73-35.09) and (OR 1.58, 95% CI 0.37-6.79), respectively. Model 3: After removing actual sexual HIV risk, MSM with high compared to low perceived risk were more willing to use PrEP (OR 6.85, 95% CI 1.23-38.05), and the HIRI-MSM general risk index was not associated with PrEP willingness (OR 1.87, 95% CI 0.54-6.54). Therefore, actual sexual HIV risk was the best predictor of PrEP willingness and general HIV risk did not inform PrEP willingness.

Willingness to use pre-exposure prophylaxis for HIV prevention among men who have sex with men in Malaysia: Findings from an online survey

PubMed Central

Pang, Joselyn; Wei, Clayton Koh Thuan; Yee, Ilias Adam; Wang, Bangyuan; Cassolato, Matteo

2017-01-01

Objective We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia. Methods An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants’ demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP. Results Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals. Conclusions Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services. PMID:28902857

Willingness to use pre-exposure prophylaxis for HIV prevention among men who have sex with men in Malaysia: Findings from an online survey.

PubMed

Lim, Sin How; Mburu, Gitau; Bourne, Adam; Pang, Joselyn; Wickersham, Jeffrey A; Wei, Clayton Koh Thuan; Yee, Ilias Adam; Wang, Bangyuan; Cassolato, Matteo; Azwa, Iskandar

2017-01-01

We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia. An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants' demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP. Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals. Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.

The cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men and transgender women at high risk of HIV infection in Brazil.

PubMed

Luz, Paula M; Osher, Benjamin; Grinsztejn, Beatriz; Maclean, Rachel L; Losina, Elena; Stern, Madeline E; Struchiner, Claudio J; Parker, Robert A; Freedberg, Kenneth A; Mesquita, Fabio; Walensky, Rochelle P; Veloso, Valdilea G; Paltiel, A David

2018-03-01

Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre-exposure prophylaxis (PrEP) programme in these populations. We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50. Mean age (31 years, SD 8.4 years), age-stratified annual HIV incidence (age ≤ 40 years: 4.3/100 PY; age > 40 years: 1.0/100 PY), PrEP effectiveness (43% HIV incidence reduction) and PrEP drug costs ($23/month) were from Brazil-based sources. The analysis focused on direct medical costs of HIV care. We measured the comparative value of PrEP in 2015 United States dollars (USD) per year of life saved (YLS). Willingness-to-pay threshold was based on Brazil's annual per capita gross domestic product (GDP; 2015: $8540 USD). Lifetime HIV infection risk among high-risk MSM and TGW was 50.5% with No PrEP and decreased to 40.1% with PrEP. PrEP increased per-person undiscounted (discounted) life expectancy from 36.8 (20.7) years to 41.0 (22.4) years and lifetime discounted HIV-related medical costs from $4100 to $8420, which led to an incremental cost-effectiveness ratio (ICER) of $2530/YLS. PrEP remained cost-effective (<1x GDP) under plausible variation in key parameters, including PrEP effectiveness and cost, initial cohort age and HIV testing frequency on/off PrEP. Daily tenofovir/emtracitabine PrEP among MSM and TGW at high risk of HIV infection in Brazil would increase life expectancy and be highly cost-effective. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

The L76V Drug Resistance Mutation Decreases the Dimer Stability and Rate of Autoprocessing of HIV-1 Protease by Reducing Internal Hydrophobic Contacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louis, John M.; Zhang, Ying; Sayer, Jane M.

2011-09-06

The mature HIV-1 protease (PR) bearing the L76V drug resistance mutation (PR{sub L76V}) is significantly less stable, with a >7-fold higher dimer dissociation constant (K{sub d}) of 71 {+-} 24 nM and twice the sensitivity to urea denaturation (UC{sub 50} = 0.85 M) relative to those of PR. Differential scanning calorimetry showed decreases in T{sub m} of 12 C for PR{sub L76V} in the absence of inhibitors and 5-7 C in the presence of inhibitors darunavir (DRV), saquinavir (SQV), and lopinavir (LPV), relative to that of PR. Isothermal titration calorimetry gave a ligand dissociation constant of 0.8 nM for DRV,more » {approx}160-fold higher than that of PR, consistent with DRV resistance. Crystal structures of PR{sub L76V} in complexes with DRV and SQV were determined at resolutions of 1.45-1.46 {angstrom}. Compared to the corresponding PR complexes, the mutated Val76 lacks hydrophobic interactions with Asp30, Lys45, Ile47, and Thr74 and exhibits closer interactions with Val32 and Val56. The bound DRV lacks one hydrogen bond with the main chain of Asp30 in PR{sub L76V} relative to PR, possibly accounting for the resistance to DRV. SQV shows slightly improved polar interactions with PR{sub L76V} compared to those with PR. Although the L76V mutation significantly slows the N-terminal autoprocessing of the precursor TFR-PR{sub L76V} to give rise to the mature PR{sub L76V}, the coselected M46I mutation counteracts the effect by enhancing this rate but renders the TFR-PRM46I/L76V precursor less responsive to inhibition by 6 {micro}M LPV while preserving inhibition by SQV and DRV. The correlation of lowered stability, higher K{sub d}, and impaired autoprocessing with reduced internal hydrophobic contacts suggests a novel molecular mechanism for drug resistance.« less

The Relationship of Adverse Childhood Events To Smoking, Overweight, Obesity and Binge Drinking Among Women In Hawaii

PubMed Central

Remigio-Baker, Rosemay A.; Hayes, Donald K.; Reyes-Salvail, Florentina

2016-01-01

OBJECTIVES To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). METHODS The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3,354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. RESULTS Overall, 54.9% reported at least 1 ACE. The prevalence of smoking (Prevalence Ratio [PR]=1.40 [1 ACE] to PR=2.55 [5+ ACEs]), overweight (PR=1.22 [1 ACE] to PR=1.31 [5+ ACEs]) and obesity (PR=1.00 [1 ACE] to PR=1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR=1.67, CI=1.26–2.22), and physical (PR=2.04, CI=1.50–2.78) and verbal (PR=1.62, CI=1.25–2.10) abuse. Obesity was also significantly related to household dysfunction (PR=1.22, CI=1.01–1.48), and physical (PR=1.36, CI=1.10–1.70), verbal (PR=1.35, CI=1.11–1.64) and sexual (PR=1.53, CI=1.25–1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR=0.26, CI=0.07, 0.93), which was significantly different from the null association among Whites (interaction p=0.02). CONCLUSION Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs. PMID:27449778

Using data from a behavioural survey of men who have sex with men (MSM) to estimate the number likely to present for HIV pre-exposure prophylaxis (PrEP) in Ireland, 2017.

PubMed

Nic Lochlainn, Laura; O'Donnell, Kate; Hurley, Caroline; Lyons, Fiona; Igoe, Derval

2017-11-01

In Ireland, men who have sex with men (MSM) have increased HIV risk. Pre-exposure prophylaxis (PrEP), combined with safe sex practices, can reduce HIV acquisition. We estimated MSM numbers likely to present for PrEP by applying French PrEP criteria to Irish MSM behavioural survey data. We adjusted for survey bias, calculated proportions accessing testing services and those likely to take PrEP. We estimated 1-3% of MSM in Ireland were likely to present for PrEP.

Unraveling Pr3+ 5d-4f emission in LiLa9(SiO4)6O2 crystals doped with Pr3+ ions

NASA Astrophysics Data System (ADS)

Ivanovskikh, Konstantin V.; Shi, Qiufeng; Bettinelli, Marco; Pustovarov, Vladimir A.

2018-05-01

LiLa9(SiO4)6O2 (LLSO) crystals doped with Pr3+ ions were grown using the slow cooling flux method. The crystals were characterized by means of luminescence and optical spectroscopy and luminescence decay measurements upon excitation in UV, VUV and X-ray range including using synchrotron radiation sources. The spectroscopic data revealed the presence Pr3+ 5d↔4f emission and excitation bands related to Pr3+ ions replacing La3+ in two nonequivalent positions, and features related Pr3+ 4f→4f emission. The photon cascade emission is not observed in LLSO:Pr3+, since Pr3+1S0 state is above the bottom of 4fn-15d mixed-states band. Apart from the emission features related to Pr3+, a defect-related emission was observed upon UV, VUV, and ionizing radiation excitation. Presence of the defects was shown with thermoluminescence measurements and suggested to be the main reason for suppression the 5d→4f emission. Peculiarities of host-to-impurity energy transfer are analyzed and discussed.

Saccharomyces cerevisiae proteinase A excretion and wine making.

PubMed

Song, Lulu; Chen, Yefu; Du, Yongjing; Wang, Xibin; Guo, Xuewu; Dong, Jian; Xiao, Dongguang

2017-11-09

Proteinase A (PrA), the major protease in Saccharomyces cerevisiae, plays an essential role in zymogen activation, sporulation, and other physiological processes in vivo. The extracellular secretion of PrA often occurs during alcoholic fermentation, especially in the later stages when the yeast cells are under stress conditions, and affects the quality and safety of fermented products. Thus, the mechanism underlying PrA excretion must be explored to improve the quality and safety of fermented products. This paper briefly introduces the structure and physiological function of PrA. Two transport routes of PrA, namely, the Golgi-to-vacuole pathway and the constitutive Golgi-to-plasma membrane pathway, are also discussed. Moreover, the research history and developments on the mechanism of extracellular PrA secretion are described. In addition, it is briefly discussed that calcium homeostasis plays an important role in the secretory pathway of proteins, implying that the regulation of PrA delivery to the plasma membrane requires the involvement of calcium ion. Finally, this review focuses on the effects of PrA excretion on wine making (including Chinese rice wine, grape wine, and beer brewage) and presents strategies to control PrA excretion.

Preferences for Long-Acting Pre-Exposure Prophylaxis (PrEP), Daily Oral PrEP, or Condoms for HIV Prevention among U.S. Men Who Have Sex with Men

PubMed Central

Greene, George J.; Swann, Greg; Fought, Angela J.; Carballo-Diéguez, Alex; Hope, Thomas J.; Kiser, Patrick F.; Mustanski, Brian; D’Aquila, Richard T.

2016-01-01

HIV prevention method preferences were evaluated among 512 U.S. men who have sex with men (MSM; median age: 22 years). Approximately 90% consistently preferred one option across pairwise comparisons of condoms, daily oral pre-exposure prophylaxis (PrEP), and long-acting PrEP delivered via either an injectable or one of two types of PrEP implants differing in visibility. Condoms were most frequently preferred (33.8%), followed by non-visible implants (21.5%), and oral PrEP (17.0%); HIV risk was reported by more choosing implants. In a follow-up question comparing the four PrEP options only, daily oral pills and non-visible implants were most frequently preferred (35.5% and 34.3%, respectively), followed by injections (25.2%) and visible implants (4.3%). An inductive, open-coding approach determined that convenience, duration of protection, and privacy were the most commonly cited reasons for a PrEP method choice, and associated with self-report of HIV risk. Tailoring PrEP product development to privacy and other concerns important to those at highest HIV risk may improve HIV prevention. PMID:27770215

Synthesis and characterization of physical properties of Gd2O2S:Pr3+ semi-nanoflower phosphor

NASA Astrophysics Data System (ADS)

Bagheri, A.; Rezaee Ebrahim Saraee, Kh.; Shakur, H. R.; Zamani Zeinali, H.

2016-05-01

Pure gadolinium oxysulfide phosphor (Gd2O2S) and trivalent praseodymium-doped gadolinium oxysulfide phosphor (Gd2O2S:Pr3+) scintillators with semi-nanoflower crystalline structures were successfully synthesized through a precipitation method and subsequent calcination treatment as a converter for X-ray imaging detectors. The characterization such as the crystal structures and nanostructure of Gd2O2S:Pr3+ scintillator measured by XRD and FeE-SEM experiment. The optical properties of Gd2O2S:Pr3+ scintillator were studied. Luminescence spectra of Gd2O2S:Pr3+ under 320 nm UV excitation show a green emission at near 511 nm corresponding to the 3P0-3H4 of Pr ions. After scintillation properties of synthesized Gd2O2S:Pr3+ scintillator investigated, Gd2O2S:Pr3+ scintillating film fabricated on a glass substrate by a sedimentation method. X-ray imaging of the fabricated scintillators confirmed that the Gd2O2S:Pr3+ scintillator could be used for radiography applications in which good spatial resolution is needed.

Genetic Determinants of Differential Oral Infection Phenotypes of West Nile and St. Louis Encephalitis Viruses in Culex spp. Mosquitoes

PubMed Central

Maharaj, Payal D.; Bolling, Bethany G.; Anishchenko, Michael; Reisen, William K.; Brault, Aaron C.

2014-01-01

St. Louis encephalitis virus (SLEV) has shown greater susceptibility to oral infectivity than West Nile virus (WNV) in Culex mosquitoes. To identify the viral genetic elements that modulate these disparate phenotypes, structural chimeras (WNV–pre-membrane [prM] and envelope [E] proteins [prME]/SLEV.IC (infectious clone) and SLEV-prME/WNV.IC) were constructed in which two of the structural proteins, the prM and E, were interchanged between viruses. Oral dose–response assessment with the chimeric/parental WNV and SLEV was performed to characterize the infection phenotypes in Culex mosquitoes by artificial blood meals. The median infectious dose required to infect 50% of Cx. quinquefasciatus with WNV was indistinguishable from that of the SLEV-prME/WNV.IC chimeric virus. Similarly, SLEV and WNV-prME/SLEV.IC virus exhibited an indistinguishable oral dose–response relationship in Cx. quinquefasciatus. Infection rates for WNV.IC and SLEV-prME/WNV.IC were significantly lower than SLEV.IC and WNV-prME/SLEV.IC infection rates. These results indicated that WNV and SLEV oral infectivities are not mediated by genetic differences within the prM and E proteins. PMID:25157120

Octarepeat region flexibility impacts prion function, endoproteolysis and disease manifestation

PubMed Central

Lau, Agnes; McDonald, Alex; Daude, Nathalie; Mays, Charles E; Walter, Eric D; Aglietti, Robin; Mercer, Robert CC; Wohlgemuth, Serene; van der Merwe, Jacques; Yang, Jing; Gapeshina, Hristina; Kim, Chae; Grams, Jennifer; Shi, Beipei; Wille, Holger; Balachandran, Aru; Schmitt-Ulms, Gerold; Safar, Jiri G; Millhauser, Glenn L; Westaway, David

2015-01-01

The cellular prion protein (PrPC) comprises a natively unstructured N-terminal domain, including a metal-binding octarepeat region (OR) and a linker, followed by a C-terminal domain that misfolds to form PrPSc in Creutzfeldt-Jakob disease. PrPC β-endoproteolysis to the C2 fragment allows PrPSc formation, while α-endoproteolysis blocks production. To examine the OR, we used structure-directed design to make novel alleles, ‘S1’ and ‘S3’, locking this region in extended or compact conformations, respectively. S1 and S3 PrP resembled WT PrP in supporting peripheral nerve myelination. Prion-infected S1 and S3 transgenic mice both accumulated similar low levels of PrPSc and infectious prion particles, but differed in their clinical presentation. Unexpectedly, S3 PrP overproduced C2 fragment in the brain by a mechanism distinct from metal-catalysed hydrolysis reported previously. OR flexibility is concluded to impact diverse biological endpoints; it is a salient variable in infectious disease paradigms and modulates how the levels of PrPSc and infectivity can either uncouple or engage to drive the onset of clinical disease. PMID:25661904

In Vitro Approach To Identify Key Amino Acids in Low Susceptibility of Rabbit Prion Protein to Misfolding

PubMed Central

Eraña, Hasier; Fernández-Borges, Natalia; Elezgarai, Saioa R.; Harrathi, Chafik; Charco, Jorge M.; Chianini, Francesca; Dagleish, Mark P.; Ortega, Gabriel; Millet, Óscar

2017-01-01

ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of rare progressive neurodegenerative disorders caused by an abnormally folded prion protein (PrPSc). This is capable of transforming the normal cellular prion protein (PrPC) into new infectious PrPSc. Interspecies prion transmissibility studies performed by experimental challenge and the outbreak of bovine spongiform encephalopathy that occurred in the late 1980s and 1990s showed that while some species (sheep, mice, and cats) are readily susceptible to TSEs, others are apparently resistant (rabbits, dogs, and horses) to the same agent. To study the mechanisms of low susceptibility to TSEs of certain species, the mouse-rabbit transmission barrier was used as a model. To identify which specific amino acid residues determine high or low susceptibility to PrPSc propagation, protein misfolding cyclic amplification (PMCA), which mimics PrPC-to-PrPSc conversion with accelerated kinetics, was used. This allowed amino acid substitutions in rabbit PrP and accurate analysis of misfolding propensities. Wild-type rabbit recombinant PrP could not be misfolded into a protease-resistant self-propagating isoform in vitro despite seeding with at least 12 different infectious prions from diverse origins. Therefore, rabbit recombinant PrP mutants were designed to contain every single amino acid substitution that distinguishes rabbit recombinant PrP from mouse recombinant PrP. Key amino acid residue substitutions were identified that make rabbit recombinant PrP susceptible to misfolding, and using these, protease-resistant misfolded recombinant rabbit PrP was generated. Additional studies characterized the mechanisms by which these critical amino acid residue substitutions increased the misfolding susceptibility of rabbit PrP. IMPORTANCE Prion disorders are invariably fatal, untreatable diseases typically associated with long incubation periods and characteristic spongiform changes associated with neuronal loss in the brain. Development of any treatment or preventative measure is dependent upon a detailed understanding of the pathogenesis of these diseases, and understanding the mechanism by which certain species appear to be resistant to TSEs is critical. Rabbits are highly resistant to naturally acquired TSEs, and even under experimental conditions, induction of clinical disease is not easy. Using recombinant rabbit PrP as a model, this study describes critical molecular determinants that confer this high resistance to transmissible spongiform encephalopathies. PMID:28978705

Sensitivity of Spaceborne and Ground Radar Comparison Results to Data Analysis Methods and Constraints

NASA Technical Reports Server (NTRS)

Morris, Kenneth R.; Schwaller, Mathew

2011-01-01

With the availability of active weather radar observations from space from the Precipitation Radar (PR) on board the Tropical Rainfall Measuring Mission (TR.MM) satellite, numerous studies have been performed comparing PR reflectivity and derived rain rates to similar observations from ground-based weather radars (GR). These studies have used a variety of algorithms to compute matching PR and GR volumes for comparison. Most studies have used a fixed 3-dimensional Cartesian grid centered on the ground radar, onto which the PR and GR data are interpolated using a proprietary approach and/or commonly available GR analysis software (e.g., SPRINT, REORDER). Other studies have focused on the intersection of the PR and GR viewing geometries either explicitly or using a hybrid of the fixed grid and PR/GR common fields of view. For the Dual-Frequency Precipitation Radar (DPR) of the upcoming Global Precipitation Measurement (GPM) mission, a prototype DPR/GR comparison algorithm based on similar TRMM PR data has been developed that defines the common volumes in terms of the geometric intersection of PR and GR rays, where smoothing of the PR and GR data are minimized and no interpolation is performed. The PR and GR volume-averaged reflectivity values of each sample volume are accompanied by descriptive metadata, for attributes including the variability and maximum of the reflectivity within the sample volume, and the fraction of range gates in the sample average having reflectivity values above an adjustable detection threshold (typically taken to be 18 dBZ for the PR). Sample volumes are further characterized by rain type (Stratiform or Convective), proximity to the melting layer, underlying surface (land/water/mixed), and the time difference between the PR and GR observations. The mean reflectivity differences between the PR and GR can differ between data sets produced by the different analysis methods; and for the GPM prototype, by the type of constraints and categorization applied to the data. In this paper, we will show results comparing the 3-D gridded analysis "black box" approach to the GPM prototype volume-matching approach, using matching TRMM PR and WSR-88D ground radar data. The affects of applying data constraints and data categorizations on the volume-matched data to the results will be shown, and explanations of the differences in terms of data and analysis algorithm characteristics will be presented. Implications of the differences to the determination of PR/DPR calibration differences and use of ground radar data to evaluate the PR and DPR attenuation correction algorithms will be discussed.

Survey of reproduction management on Canadian dairy farms.

PubMed

Denis-Robichaud, J; Cerri, R L A; Jones-Bitton, A; LeBlanc, S J

2016-11-01

The objectives of this study were to (1) quantify current reproduction management practices, and (2) assess the association between these practices and herd reproductive performance on dairy farms in Canada. A bilingual survey was developed, validated, and administered from March to May 2014 to collect general and reproduction management and performance measures [annual 21-d pregnancy rate (PR), 21-d insemination rate (IR), and conception risk (CR)]. Associations between management practices and reproductive performance measures were tested using linear regression models. A total of 832 questionnaires were completed online and by mail, representing a response rate of 9%. On average, farms had 77 lactating cows (median=50) and 13 dry cows (median=10), and Holstein was the most common breed (92% of herds). Lactating cow housing was tiestall on 61% of the farms, freestall on 37%, and bedded pack on 2%. The average voluntary waiting period was 58 d in milk (DIM). The main reproduction management practice per farm was defined as the means employed for >50% of inseminations. Farms reported their main reproduction management practice for first and subsequent inseminations, respectively, as visual estrus detection (51 and 44% of herds), timed AI (21 and 23% of herds), automated activity monitoring (AAM; 10 and 10% of herds), other management practice (bulls; 2 and 2% of herds), and a combination of management practices (16 and 21% of herds). On farms using visual estrus detection, cows were observed for signs of estrus on average 3.5 times per day, for an average total of 36 min/d. The most common use of reproductive hormones was to synchronize ovulation using Ovsynch (58% of the farms). Average PR, IR, and CR were 17.6, 44.1, and 40.5%, respectively. In linear regression analyses adjusted for confounders, pregnancy rate was significantly associated with geographic region, housing (tiestall: PR=15.4%, freestall: PR=17.6%), herd size (<50 lactating cows: PR=16.2%, 50-100 cows: PR=16.5%, >100 cows: PR=17.8%), voluntary waiting period (≤60 DIM: PR=17.6%, >60 DIM: PR=15.9%), and frequency of insemination per day (once daily: PR=16.6%, twice or more daily: PR=18.1%). The main reproduction management practice at first and subsequent inseminations was divergently associated with IR and CR, but not with PR (visual heat detection: PR=17.4%, timed AI: PR=18.4%, AAM: PR=17.1%, combined practices: PR=18.2%). Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Oral Pre-Exposure Prophylaxis (PrEP) for Prevention of HIV in Serodiscordant Heterosexual Couples in the United States: Opportunities and Challenges

PubMed Central

Myers, Julie E.; Kurth, Ann E.; Cohen, Stephanie E.; Mannheimer, Sharon B.; Simmons, Janie; Pouget, Enrique R.; Trabold, Nicole; Haberer, Jessica E.

2014-01-01

Abstract Oral HIV pre-exposure prophylaxis (PrEP) is a promising new biomedical prevention approach in which HIV-negative individuals are provided with daily oral antiretroviral medication for the primary prevention of HIV-1. Several clinical trials have demonstrated efficacy of oral PrEP for HIV prevention among groups at high risk for HIV, with adherence closely associated with level of risk reduction. In the United States (US), three groups have been prioritized for initial implementation of PrEP—injection drug users, men who have sex with men at substantial risk for HIV, and HIV-negative partners within serodiscordant heterosexual couples. Numerous demonstration projects involving PrEP implementation among MSM are underway, but relatively little research has been devoted to study PrEP implementation in HIV-serodiscordant heterosexual couples in the US. Such couples face a unique set of challenges to PrEP implementation at the individual, couple, and provider level with regard to PrEP uptake and maintenance, adherence, safety and toxicity, clinical monitoring, and sexual risk behavior. Oral PrEP also provides new opportunities for serodiscordant couples and healthcare providers for primary prevention and reproductive health. This article provides a review of the critical issues, challenges, and opportunities involved in the implementation of oral PrEP among HIV-serodiscordant heterosexual couples in the US. PMID:25045996

Prion Protein Does Not Confer Resistance to Hippocampus-Derived Zpl Cells against the Toxic Effects of Cu2+, Mn2+, Zn2+ and Co2+ Not Supporting a General Protective Role for PrP in Transition Metal Induced Toxicity

PubMed Central

Cingaram, Pradeep Kumar Reddy; Nyeste, Antal; Dondapati, Divya Teja; Fodor, Elfrieda; Welker, Ervin

2015-01-01

The interactions of transition metals with the prion protein (PrP) are well-documented and characterized, however, there is no consensus on their role in either the physiology of PrP or PrP-related neurodegenerative disorders. PrP has been reported to protect cells from the toxic stimuli of metals. By employing a cell viability assay, we examined the effects of various concentrations of Cu2+, Zn2+, Mn2+, and Co2+ on Zpl (Prnp -/-) and ZW (Prnp +/+) hippocampus-derived mouse neuronal cells. Prnp -/- Zpl cells were more sensitive to all four metals than PrP-expressing Zw cells. However, when we introduced PrP or only the empty vector into Zpl cells, we could not discern any protective effect associated with the presence of PrP. This observation was further corroborated when assessing the toxic effect of metals by propidium-iodide staining and fluorescence activated cell sorting analysis. Thus, our results on this mouse cell culture model do not seem to support a strong protective role for PrP against transition metal toxicity and also emphasize the necessity of extreme care when comparing cells derived from PrP knock-out and wild type mice. PMID:26426582

Pressure ulcer treatment in pediatric patients.

PubMed

Schlüer, Anna-Barbara; Schols, Jos M G A; Halfens, Ruud J G

2013-11-01

To assess pressure ulcer (PrU) treatment in Swiss hospitalized pediatric patients and to determine whether there are differences in PrU treatment, according to demographic characteristics of the patients. A descriptive multicenter point prevalence study was conducted in June 2009 in all German-speaking pediatric hospitals in Switzerland. All hospitalized patients from birth up to 17 years or younger in 14 Swiss pediatric hospitals, including all pediatric departments, were assessed. A total of 412 patients participated in this study. The instrument and method of the Dutch National Prevalence Measurement of Care Problems were used. Thirty-five percent of the patients had a PrU. Almost all of these PrUs (94.1%) were of category 1. The most severe PrUs occurred in patients older than 8 years. Age of the patient and department were the only characteristics that significantly influenced the occurrence of PrU categories 2 to 4. Pressure ulcer categories 2 to 4 were mostly covered with hydrocolloid or polyurethane foam dressings. No pediatric-specific guideline regarding PrU treatment is used in the involved hospitals. Most patients had category 1 PrUs, so appropriate prevention to decrease any further trauma in these patients was necessary. Severe PrUs (categories 2-4) are mostly limited to older pediatric (aged >8 years) patients with chronic conditions or after surgery intervention. A PrU treatment guideline adapted for pediatric needs is recommended.

De novo generation of infectious prions with bacterially expressed recombinant prion protein.

PubMed

Zhang, Zhihong; Zhang, Yi; Wang, Fei; Wang, Xinhe; Xu, Yuanyuan; Yang, Huaiyi; Yu, Guohua; Yuan, Chonggang; Ma, Jiyan

2013-12-01

The prion hypothesis is strongly supported by the fact that prion infectivity and the pathogenic conformer of prion protein (PrP) are simultaneously propagated in vitro by the serial protein misfolding cyclic amplification (sPMCA). However, due to sPMCA's enormous amplification power, whether an infectious prion can be formed de novo with bacterially expressed recombinant PrP (rPrP) remains to be satisfactorily resolved. To address this question, we performed unseeded sPMCA with rPrP in a laboratory that has never been exposed to any native prions. Two types of proteinase K (PK)-resistant and self-perpetuating recombinant PrP conformers (rPrP-res) with PK-resistant cores of 17 or 14 kDa were generated. A bioassay revealed that rPrP-res(17kDa) was highly infectious, causing prion disease in wild-type mice with an average survival time of about 172 d. In contrast, rPrP-res(14kDa) completely failed to induce any disease. Our findings reveal that sPMCA is sufficient to initiate various self-perpetuating PK-resistant rPrP conformers, but not all of them possess in vivo infectivity. Moreover, generating an infectious prion in a prion-free environment establishes that an infectious prion can be formed de novo with bacterially expressed rPrP.

Estrogen and progesterone receptors in normal cervix and primary cervical carcinoma.

PubMed

Shen, K; Yueng, W; Ngan, H

1994-09-01

Estrogen and progesterone receptors (ER, PR) were measured in 21 specimens of cervical cancer and in 17 specimens of normal cervix by monoclonal enzyme immunoassay (EIA). In normal cervix, 88.2% of specimens were ER-positive ( > 15 fmol/mg protein), 74.5% were PR-positive ( > 15 fmol/mg protein) and 74.5% were both ER- and PR-positive. In cervical cancer, 66.7% were ER-positive, 42.9% were PR-positive and 38.1% were both ER- and PR- positive. There was no significant difference in ER status between the normal cervix and cervical cancer (P > 0.05), but PR status and levels in normal cervix were significantly higher than those in cervical carcinoma (P < 0.05). ER levels in squamous cell carcinoma was not correlated to the tumor stage, histologic grade and menopausal status. PR levels in premenopausal patients with squamous cell carcinoma were significantly higher than those in postmenopausal patients (P < 0.01). Adenocarcinoma of the cervix contained significantly more ER and PR than squamous cell carcinoma (P < 0.01, P < 0.05). In addition, serum E2 level was also assayed in 21 patients with cervical cancer. There was significant difference in E2 levels between the premenopausal and postmenopausal patients (P < 0.01). Patients were stratified according to E2 levels, a significant difference in PR levels and in the ratio of PR/ER was noted (P < 0.05, P < 0.01).

Minimal Awareness and Stalled Uptake of Pre-Exposure Prophylaxis (PrEP) Among at Risk, HIV-Negative, Black Men Who Have Sex with Men

PubMed Central

Driffin, Daniel D.; Bauermeister, Jose; Smith, Harlan; Conway-Washington, Christopher

2015-01-01

Abstract In the United States, rates of HIV infection are highest among black men who have sex with men (BMSM). Pre-exposure prophylaxis (PrEP) is a highly effective form of HIV prevention, but the uptake of this strategy has been slow since FDA approval in 2012, and it is unknown whether information about PrEP is reaching BMSM. Four hundred and thirty-six BMSM in Atlanta, GA were surveyed from January 2012 (6 months prior to PrEP approval) to March 2014 (20 months after approval). Analyses revealed no association between date of survey assessment and awareness of PrEP (20.5% were aware of PrEP before approval and 23.4% were aware after approval; OR=0.99 [0.98–1.02], p=0.952). In a multivariate model, BMSM unaware of PrEP reported lower rates of HIV testing knowledge, fewer experiences with HIV testing, and higher rates of transactional sex than BMSM who were aware of PrEP. Our findings suggest that there is limited understanding of PrEP and that there is considerable groundwork that needs to be achieved in order to reap the full benefits of PrEP. The current findings call attention to the need to both prioritize and better understand how to strengthen the bridge between medical advances and community uptake. PMID:26083143

Analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides

PubMed Central

Guichard, Cécile; Ivanyi-Nagy, Roland; Sharma, Kamal Kant; Gabus, Caroline; Marc, Daniel; Mély, Yves; Darlix, Jean-Luc

2011-01-01

Prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (PrPC) into the aggregated misfolded scrapie isoform, named PrPSc. Recent studies on the physiological role of PrPC revealed that this protein has probably multiple functions, notably in cell–cell adhesion and signal transduction, and in assisting nucleic acid folding. In fact, in vitro findings indicated that the human PrP (huPrP) possesses nucleic acid binding and annealing activities, similarly to nucleic acid chaperone proteins that play essential roles in cellular DNA and RNA metabolism. Here, we show that a peptide, representing the N-terminal domain of huPrP, facilitates nucleic acid annealing by two parallel pathways nucleated through the stem termini. We also show that PrP of human or ovine origin facilitates DNA strand exchange, ribozyme-directed cleavage of an RNA template and RNA trans-splicing in a manner similar to the nucleocapsid protein of HIV-1. In an attempt to characterize inhibitors of PrP-chaperoning in vitro we discovered that the thioaptamer 5′-GACACAAGCCGA-3′ was extensively inhibiting the PrP chaperoning activities. At the same time a recently characterized methylated oligoribonucleotide inhibiting the chaperoning activity of the HIV-1 nucleocapsid protein was poorly impairing the PrP chaperoning activities. PMID:21737432

Pinoresinol reductase 1 impacts lignin distribution during secondary cell wall biosynthesis in Arabidopsis

DOE PAGES

Zhao, Qiao; Zeng, Yining; Yin, Yanbin; ...

2014-08-05

In this paper, pinoresinol reductase (PrR) catalyzes the conversion of the lignan (-)-pinoresinol to (-)-lariciresinol in Arabidopsis thaliana, where it is encoded by two genes, PrR1 and PrR2, that appear to act redundantly. PrR1 is highly expressed in lignified inflorescence stem tissue, whereas PrR2 expression is barely detectable in stems. Co-expression analysis has indicated that PrR1 is co-expressed with many characterized genes involved in secondary cell wall biosynthesis, whereas PrR2 expression clusters with a different set of genes. The promoter of the PrR1 gene is regulated by the secondary cell wall related transcription factors SND1 and MYB46. The loss-of-function mutantmore » of PrR1 shows, in addition to elevated levels of pinoresinol, significantly decreased lignin content and a slightly altered lignin structure with lower abundance of cinnamyl alcohol end groups. Stimulated Raman scattering (SRS) microscopy analysis indicated that the lignin content of the prr1-1 loss-of-function mutant is similar to that of wild-type plants in xylem cells, which exhibit a normal phenotype, but is reduced in the fiber cells. Finally, together, these data suggest an association of the lignan biosynthetic enzyme encoded by PrR1 with secondary cell wall biosynthesis in fiber cells.« less