bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of drought and UV radiation impacts on above-ground biomass of mountain grassland by spectral reflectance and thermal imaging techniques
Authors: Novotná Kateřina , Klem Karel , Holub Petr , Rapantová Barbora , Urban Otmar
Published: February 2017

Drought represents one of the major factors limiting productivity of managed and natural ecosystems. Under natural field conditions drought is often associated with other stress factors such as high temperature and UV radiation, which may result in enhancement or vice versa alleviation of drought impact. Remote sensing methods have a large potential to evaluate impacts of drought on plant production at regional scale. The main objective of this study was to analyse the potential of ground-based measurement of spectral reflectance and thermal imaging for monitoring the impacts of drought and UV radiation on above-ground biomass production of mountain grassland ecosystem. Experimental rain-out shelters were used to manipulate incident precipitation and UV radiation for 7 weeks (May–July). A canopy spectral reflectance, thermal images, and total above-ground biomass were determined at the end of drought and UV treatment. Results show that drought led to a significant reduction of above-ground biomass, particularly under ambient UV radiation. In contrary, UV had only negligible effect on biomass production. Canopy temperature as well as selected spectral reflectance indices showed significant response to drought stress and also significant relationships to above-ground biomass. However, the relationship between canopy temperature and above-ground biomass is modified by UV radiation. Best prediction of changes in biomass caused by drought stress was provided by vegetation index NDVI.
Requirement of extracellular Ca2+ binding to specific amino acids for heat‐evoked activation of TRPA1
Authors: Kurganov Erkin , Saito Shigeru , Tanaka Saito Claire , Tominaga Makoto
Published: February 2017

Key points

We found that extracellular Ca2+, but not other divalent cations (Mg2+ and Ba2+) or intracellular Ca2+, is involved in heat‐evoked activation of green anole (ga) TRPA1.

Heat‐evoked activation of chicken (ch) and rat snake (rs) TRPA1 does not depend solely on extracellular Ca2+.

Neutralization of acidic amino acids on the outer surface of TRPA1 by extracellular Ca2+ is important for heat‐evoked large activation of gaTRPA1, chTRPA1 and rsTRPA1.

Transient receptor potential ankyrin 1 (TRPA1) is a homotetrameric non‐selective cation‐permeable channel that has six transmembrane domains and cytoplasmic N‐ and C‐termini. The N‐terminus is characterized by an unusually large number of ankyrin repeats. Although the 3‐dimensional structure of human TRPA1 has been determined, and TRPA1 channels from insects to birds are known to be activated by heat stimulus, the mechanism for temperature‐dependent TRPA1 activation is unclear. We previously reported that extracellular Ca2+, but not intracellular Ca2+, plays an important role in heat‐evoked TRPA1 activation in green anole lizards (gaTRPA1). Here we focus on extracellular Ca2+‐dependent heat sensitivity of gaTRPA1 by comparing gaTRPA1 with heat‐activated TRPA1 channels from rat snake (rsTRPA1) and chicken (chTRPA1). In the absence of extracellular Ca2+, rsTRPA1 and chTRPA1 are activated by heat and generate small inward currents. A comparison of extracellular amino acids in TRPA1 identified three negatively charged amino acid residues (glutamate and aspartate) near the outer pore vestibule that are involved in heat‐evoked TRPA1 activation in the presence of extracellular Ca2+. These results suggest that neutralization of acidic amino acids by extracellular Ca2+ is important for heat‐evoked activation of gaTRPA1, chTRPA1, and rsTRPA1, which could clarify mechanisms of heat‐evoked channel activation.
Mass Optimization of a Supercritical CO2 Brayton Cycle Power Conversion System for a Mars Surface Fission Power Reactor
Authors: Harris Kurt E. , Schillo Kevin J. , Hew Yayu M. , Kumar Akansha , Howe Steven D.
Published: February 2017

In the National Aeronautics and Space Administration (NASA) Design Reference Architecture 5.0 (DRA 5.0), fission surface power systems (FSPS) are described as “enabling for the human exploration of Mars.” This study investigates the design of a power conversion system (PCS) based on supercritical carbon dioxide (sCO2) Brayton configurations for a growing Martian colony. Various configurations utilizing regeneration, intercooling (IC), and reheating are analyzed. A model to estimate the mass of the PCS is developed and used to obtain a realistic mass-optimized configuration. This mass model is conservative, being based on simple concentric tube counterflow heat exchangers and published data regarding turbomachinery masses. For load following and redundancy purposes, the FSPS consists of three 333 kWe reactors and PCS to provide a total of 1 MWe for 15 years. The optimal configuration is a sCO2 Brayton cycle with 60% regeneration and two stages of intercooling. The majority of the analyses are performed in matlab, with certain data provided by a comsol multiphysics model of part of a low-enriched uranium (LEU) ceramic metallic (CERMET) reactor core.
Two Circular-Hole Cracks of the Same Size in an Infinite Plate in Tension
Authors: Miao Changqing , Wei Yintao , Yan Xiangqiao
Published: February 2017

This note is concerned with two circular-hole cracks of the same size in an infinite plate in tension by means of the generation of Bueckner's principle and the hybrid displacement discontinuity method. Many numerical results which can reveal the interactions of two circular-hole cracks are given.
2. Jacob and Wilhelm Grimm: Kinder- und Hausmärchen
Authors: -- --
Published: February 2017

Parody Grimm Fairy Tales
4.1 James Thurber: 'The Little Girl and the Wolf'
Authors: -- --
Published: February 2017

Parody Grimm Thurber Rotkäppchen
5. Discussion
Authors: -- --
Published: February 2017

Parody Grimm Fairy Tales
6. Bibliography
Authors: -- --
Published: February 2017

Parody Grimm Fairy Tales
Karl Wolfskehls INRI-Zyklus
Authors: Franke Norman P.
Published: February 2017

Wolfskehl
Erinnerte "Wirklichkeit" und erzählte "Fiktion": Das Neuseeland der Otti Binswanger in den Jahren 1939-1948
Authors: Wittmann Livia Käthe
Published: February 2017

Wolfskehl, Otti Binswanger, Neuseeland
Vorbemerkung
Authors: -- --
Published: February 2017

Fontane
Vorwort
Authors: Obermayer August
Published: February 2017

Vorwort
Wien versus Österreich oder Die Spannung zwischen Hofmannsthal und Schnitzler
Authors: Nehring Wolfgang
Published: February 2017

Wien, Österreich, Hofmannsthal, Schnitzler
Using the 2016 Transit of Mercury to Find the Distance to the Sun
Authors: Pasachoff Jay M. , Gährken Bernd , Schneider Glenn
Published: February 2017

The May 9, 2016, transit of Mercury was observed simultaneously from the Big Bear Solar Observatory in California and from a site in Germany. From the measured displacement between the views from the two sites of Mercury’s disk silhouetted against the solar granulation, we were able to calculate the distance to the Sun in linear units (kilometers), not merely the proportionality given by Kepler’s third law.
An Easy Way to One-Dimensional Elastic Collisions
Authors: Sztrajman Jorge , Sztrajman Alejandro
Published: February 2017

The aim of this paper is to propose a method for solving head-on elastic collisions, without algebraic complications, to emphasize the use of the fundamental conservations laws. Head-on elastic collisions are treated in many physics textbooks as examples of conservation of momentum and kinetic energy:
Transition Matrices: A Tool to Assess Student Learning and Improve Instruction
Authors: Morris Gary A. , Walter Paul , Skees Spencer , Schwartz Samantha
Published: February 2017

This paper introduces a new spreadsheet tool for adoption by high school or college-level physics teachers who use common assessments in a pre-instruction/post-instruction mode to diagnose student learning and teaching effectiveness. The spreadsheet creates a simple matrix that identifies the percentage of students who select each possible pre-/post-test answer combination on each question of the diagnostic exam. Leveraging analysis of the quality of the incorrect answer choices, one can order the answer choices from worst to best (i.e., correct), resulting in “transition matrices” that can provide deeper insight into student learning and the success or failure of the pedagogical approach than traditional analyses that employ dichotomous scoring.
A Student View of Experimental Physics
Authors: Bu Frank , Marlowe Robert Lloyd , Whitson Kristin
Published: February 2017

This is the story of how an enterprising high school student came to my lab one afternoon, asking if there were any way that he could gain “hands-on” lab experience by working with me. While I had some doubts about allowing him to work in an area with an expensive 150-mW focused laser beam, I eventually said yes. I was well aware that a couple of weeks of lab work could lead to interesting investigations for him….
Significant Figures in Measurements with Uncertainty: A Working Criterion
Authors: Vilchis Abraham
Published: February 2017

Generally speaking, students have difficulty reporting out measurements and estimates of quantities used in the laboratory, and with handling the significant figures associated with them. When required to make calculation involving quantities with different numbers of significant figures, they have difficulty in assigning the corresponding digits to the final result. When in addition, the quantities have uncertainty, the operations entailed pose an even greater challenge. The article advocates for some working rules for students (and teachers) in an effort to combat this problem.
Entropic Damping of the Motion of a Piston
Authors: Mungan Carl E.
Published: February 2017

The concept of an “entropic force” can be introduced by considering a familiar setup, namely a horizontal cylinder enclosing an ideal monatomic gas by a piston of cross-sectional area A and mass m that can slide without friction. The surrounding atmospheric pressure Patm keeps the piston from flying out of the cylinder. The cylinder and piston have negligible heat capacity (compared to the gas), but the gas is not thermally insulated from the surroundings at room temperature TR. Ignore any viscosity or turbulence of the enclosed gas or surrounding air. Two specific and illustrative situations are analyzed here. In the first, the piston is massless, m = 0. The piston is temporarily held in place by a pin while the gas is quickly adjusted to initial pressure Pi = Patm and temperature slightly larger than that of the room, say Ti = 1.1TR, using a heater and regulator. The piston is then released from rest, vi = 0. In the second case, the piston has inertia, m > 0, and the gas is initially in both mechanical and thermal equilibrium with the surroundings so that Pi = Patm and Ti = TR. The piston is now given a quick inward push, vi < 0. In both situations, the aim is the same: Describe the subsequent evolution of the system.
Size of undergraduate physics & astronomy programs
Authors: White Susan C.
Published: February 2017

Last month we used the number of bachelor’s degrees awarded per fulltime equivalent (FTE) faculty member to examine PhD-granting physics departments. The Statistical Research Center has recently published a new report that provides these data for all departments that offer bachelor’s degrees. This graph shows the average number of degrees by FTE faculty for physics departments that do not offer any graduate degrees. Similar data are provided for departments that offer graduate degrees and for astronomy departments The report is available at .
Effects of linguistic experience on the perception of high-variability non-native tones
Authors: Chang Yung-hsiang Shawn , Yao Yao , Huang Becky H.
Published: February 2017

Whether tone language experience facilitates non-native tone perception is an area of research that previously yielded conflicting results, potentially because of the lack of systematical control of speaker normalization effects across studies. Under a high-variability testing condition with controlled speaker normalization cues, Cantonese (native controls), Mandarin (Cantonese-naive tone listeners), and English (non-tone listeners) listeners identified three Cantonese level tones. The results indicate a facilitatory effect of tone experience on non-native tone perception when normalization for inter-speaker variation is required.
Speech enhancement via two-stage dual tree complex wavelet packet transform with a speech presence probability estimator
Authors: Sun Pengfei , Qin Jun
Published: February 2017

In this paper, a two-stage dual tree complex wavelet packet transform (DTCWPT) based speech enhancement algorithm has been proposed, in which a speech presence probability (SPP) estimator and a generalized minimum mean squared error (MMSE) estimator are developed. To overcome the drawback of signal distortions caused by down sampling of wavelet packet transform (WPT), a two-stage analytic decomposition concatenating undecimated wavelet packet transform (UWPT) and decimated WPT is employed. An SPP estimator in the DTCWPT domain is derived based on a generalized Gamma distribution of speech, and Gaussian noise assumption. The validation results show that the proposed algorithm can obtain enhanced perceptual evaluation of speech quality (PESQ), and segmental signal-to-noise ratio (SegSNR) at low signal-to-noise ratio (SNR) nonstationary noise, compared with four other state-of-the-art speech enhancement algorithms, including optimally modified log-spectral amplitude (OM-LSA), soft masking using a posteriori SNR uncertainty (SMPO), a posteriori SPP based MMSE estimation (MMSE-SPP), and adaptive Bayesian wavelet thresholding (BWT).
Estimating Measurement Validity: A Tutorial
Authors: Yun Joonkoo , Ulrich Dale A.
Published: February 2017

The purposes of this tutorial are threefold: (a) to clarify the meaning of measurement validity, (b) to provide appropriate validation procedures for use by researchers in adapted physical activity, and (c) to raise the awareness of the limitations of the traditional views on measurement validity. Several validation procedures are described with specific examples from adapted physical activity research based on traditional approaches of providing validity evidence. Conceptual and empirical limitations of the traditional validity framework are discussed. We recommend that several categories of validity evidence should be reported in research studies. We encourage practicing the unified concept of measurement validity (Messick, 1993, 1995) in adapted physical activity research and practice.
Empowerment Through the Sport Context: A Model to Guide Research for Individuals with Disability
Authors: Pensgaard Anne Marte , Sorensen Marit
Published: February 2017

Our purpose is to propose a model of “Empowerment through the sport context” to guide psychosocial research in disability sport. We discuss the concept of empowerment in relation to sport for individuals with disabilities. Expanding upon the work of Hutzler (1990), we include three levels of empowerment (societal, group, and individual level) in our approach. Important moderators are age of onset of disability, gender, and type of disability. Important mediators are (a) at the individual level, achievement goals, identity, and self-efficacy; (b) at the group level, motivational climate, group identity, and collective efficacy; and finally, (c) at the societal level, the cultural context and political efficacy. Several methodological considerations are discussed, and various solutions are suggested. We also discuss the critiques that have emerged in relation to the use of the empowerment concept.
Underwater Weighing Familiarization Program for Adults with Prader-Willi Syndrome
Authors: Draheim Christopher C. , Bakke Bruce L. , Serfass Robert C. , Snyder Paul V. , Walker Ava J.
Published: February 2017

The purpose of the project was to evaluate an underwater weighing (UWW) and residual lung volume (RV) familiarization program developed for adults with Prader-Willi syndrome (PWS). UWW was conducted on 15 adults (10 men, 5 women) with PWS following a UWW familiarization program. Repeated measures ANOVA revealed no difference in percent body fat derived from UWW over the four sessions, F(3, 27) = 0.80, p = .505, with an intraclass reliability coefficient of R = .93. There was, however, a significant difference in RV, F(3, 27) = 5.25, p = .006, with an intraclass reliability coefficient of R = .65. The familiarization program is recommended for implementation prior to measuring percent body fat via UWW. However, predicting the RV may be an easier and more consistent alternative to measuring the RV in adults with PWS.
Free Throw Shooting Technique of Male Wheelchair Basketball Players
Authors: Goosey-Tolfrey Victoria , Butterworth Daniel , Morriss Calvin
Published: February 2017

Three-dimensional kinematic data were obtained from 15 male wheelchair basketball players performing a successful free throw. Players were divided into two groups, according to their International Wheelchair Basketball Federation (IWBF) classification (Group 1: 2-2.5 point players and Group 2: 4-4.5 point players). The angle of release of the ball was 58 for both groups. Group 2 released the ball from a significantly greater height than Group 1 (1.57 – 0.12m v 1.78 – 0.17m; p < .05). Although nonsignificant, the following trends were found: Group 1 showed greater ball release speeds and generated greater angular velocity of the wrist at release while Group 2 generated greater shoulder flexion angular velocity at release. In conclusion, players from different IWBF classes tend to rely on different kinematic strategies to produce successful release conditions.
The Consultation Process: Adapted Physical Education Specialists’ Perceptions
Authors: Lytle Rebecca K. , Collier Doug
Published: February 2017

The purpose was to examine adapted physical education (APE) specialists’ perceptions about consultation as a delivery model for individuals with disabilities. Six APE specialists (4 female, 2 male) from California participated in this phenomenological study. Data came from in-depth individual interviews, field observations, researcher notes, and focus group interactions. Analysis revealed distinct categories related to consultation: definition, contextual factors, effectiveness (benefits, barriers, documentation), competency, training, and consultation model preferences. Consultation interactions varied greatly because of the dynamic nature of the educational environment. The use of consultation was more prevalent with middle and high school students. Adapted physical education consultation occurred on a continuum from proximal to distal, dependent on the degree of interaction between the APE specialist, the general education (GE) teacher, and the student. The effectiveness of consultation was dependent upon the GE teacher’s attitude and the APE specialist’s communication skills and competencies.
Perceived Barriers to Including Students with Visual Impairments in General Physical Education
Authors: Lieberman Lauren J. , Houston-Wilson Cathy , Kozub Francis M.
Published: February 2017

The purpose of this study was to examine barriers perceived by teachers when including students with visual impairments in general physical education. Teachers (52 males, 96 females) who had children with visual impairments in their physical education classes were surveyed prior to in-service workshop participation. The most prevalent barriers were professional preparation, equipment, programming, and time. A logistic regression analysis, regressing gender, in-service training, number of students with visual impairments taught, masters degree attained, masters hours spent on visual impairments (yes or no), undergraduate hours spent on visual impairments (yes or no), and years of experience failed to indicate significant predictors of professional preparation as a barrier, Model χ2 (6, n = 148) = 4.48, p > .05.
Perceptions of Adapted Physical Education Graduates From Selected Universities on Attainment of Doctoral Competencies
Authors: Porretta David L. , Surburg Paul R. , Jansma Paul
Published: February 2017

Graduates from four adapted physical education doctoral programs (1980-1999) within the United States were surveyed to determine their perceptions on the extent to which they attained published competencies in the areas of research and adapted physical education. A survey was mailed to 109 doctoral program graduates. A total of 99 surveys (91%) were usable for data analysis. Competency data were analyzed separately across two 10-year time periods (1980-1989; 1990-1999). Respondents’ perceptions improved significantly in cumulative research competency scores from the first to the second time period. Responses for adapted physical education competencies were similar across both time periods. Follow-up analyses on responses for each of the separate 18 research and 20 adapted physical education competency statements resulted in significant improvement from 1980-1989 to 1990-1999 for eight research competencies and one adapted physical education competency. Results have implications for the future of adapted physical education doctoral training in the United States and beyond.
Sport Participation of Hong Kong Chinese Children with Disabilities in Special Schools
Authors: Sit Cindy H.P. , Lindner Koenraad J. , Sherrill Claudine
Published: February 2017

The purpose was to examine sport participation (excluding physical education classes) of school-aged Chinese children with disabilities attending special schools in Hong Kong. A sample of 237 children, ages 9 to 19, attending 10 special schools in Hong Kong, responded to a sport participation questionnaire in individual interviews. Data were analyzed by gender, two school levels, and five disability types. Results relating to participation frequency and extent indicated that girls were significantly less active than boys. Children with physical disability, visual impairment, and mental disability were less active than children with hearing impairment and maladjustment. Children with different types of disabilities varied in their participation patterns and choices of physical activities as well as their motives for sport participation, nonparticipation, and withdrawal. We concluded that disability type is more related to children’s participation behaviors in sport and physical activities than to gender and school level.
Friendship Quality in Youth Disability Sport: Perceptions of a Best Friend
Authors: Martin Jeffrey J. , Smith Kerry
Published: February 2017

The purpose of the current investigation was to examine friendship quality with a best friend in youth disability sport with an international sample of moderately experienced athletes with disabilities ages 9 to 18 years. Participants were 85 males and 65 females from four countries who competed in track and field and swimming. Data were collected with the Sport Friendship Quality Scale (Weiss & Smith, 1999). An exploratory factor analyses indicated that participants viewed their friendship quality with a best friend in disability sport as having both positive and negative dimensions. The latter focused exclusively on conflict experiences. Females reported stronger perceptions of the benefits of their friendships than males did; whereas no gender differences occurred in perceptions of the negative aspects to friendships. Item analyses indicated that females scored higher than males on questions reflecting loyalty, providing intimacy, self-esteem, supportiveness, having things in common, and playing together.
Physiological Responses of Endurance-Trained Male Wheelchair Athletes to a 10-Kilometer Treadmill Time Trial
Authors: Campbell Ian G. , Williams Clyde , Lakomy Henryk K.A.
Published: February 2017

The purpose was to examine selected physiological responses of endurance-trained male wheelchair athletes in different Paralympic racing classes (T2, n = 3; T3, n = 8; T4, n = 7) during a 10-km treadmill time trial (TM:10-km). Peak oxygen uptake (V̇O2 peak) was determined, and a TM:10-km was completed on a motorized treadmill. From this, % V̇O2peak utilized and the relationship between V̇O2peak and TM:10-km were established. During the TM:10-km, the following dependent variables were examined: propulsion speed, oxygen uptake, respiratory exchange ratio, and heart rate. The results showed athletes utilize a high % V̇O2peak (78.4 –13.6%) during the TM:10-km. There was a moderate correlation (r = -.57, p < .01) between VO2peak and TM:10-km. No physiological differences were found between the paraplegic racing classes (T3, T4), which suggests that there is some justification in amalgamating these racing classes for endurance events.
Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs
Authors: Gunsaru Bornface , Burgess Steven J. , Morrill Westin , Kelly Jane X. , Shomloo Shawheen , Smilkstein Martin J. , Liebman Katherine , Peyton David H.
Published: February 2017

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from
in vitro
heme binding and
β
-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against
Plasmodium falciparum
similar to those of CQ, although other mechanisms of action may be relevant to their activities.
Results from a Patient-Based Health Education Intervention in Reducing Antibiotic Use for Acute Upper Respiratory Tract Infections in the Private Sector Primary Care Setting in Singapore
Authors: Lee Magdalene Hui Min , Pan Darius Shaw Teng , Huang Joyce Huixin , Chen Mark I-Cheng , Chong Joash Wen Chen , Goh Ee Hui , Jiang Lili , Leo Yee Sin , Lee Tau Hong , Wong Chia Siong , Loh Victor Weng Keong , Lim Fong Seng , Poh Adrian Zhongxian , Tham Tat Yean , Wong Wei Mon , Yu Yue
Published: February 2017

We investigated the efficacy of patient-targeted education in reducing antibiotic prescriptions for upper respiratory tract infections (URTIs) among adults in the private primary care setting in Singapore. Our randomized controlled trial enrolled patients aged 21 years and above presenting at general practitioner (GP) clinics with URTI symptoms for 7 days or less. Intervention arm patients were verbally educated via pamphlets about the etiology of URTIs, the role of antibiotics in treating URTIs, and the consequences of inappropriate antibiotic use. Control arm patients were educated on influenza vaccinations. Both arms were compared regarding the proportions prescribed antibiotics and the patients' postconsultation views. A total of 914 patients consulting 35 doctors from 24 clinics completed the study (457 in each arm). The demographics of patients in both arms were similar, and 19.1% were prescribed an antibiotic, but this varied from 0% to 70% for individual GPs. The intervention did not significantly reduce antibiotic prescriptions (odds ratio [OR], 1.20; 95% confidence interval [CI], 0.83–1.73) except in patients of Indian ethnicity (OR, 0.28; 95% CI, 0.09–0.93). Positive associations between the intervention and the view that antibiotics were not needed most of the time for URTIs (
P
= 0.047) and on being worried about the side effects of antibiotics (
P
= 0.018) were restricted to the Indian subgroup. GPs in limited liability partnerships or clinic chains prescribed less (OR, 0.36; 95% CI, 0.14 to 0.92), while certain inappropriate patient responses were associated with the receipt of antibiotics. Follow-up studies to investigate differences in responses to educational programs between ethnicities and to explore GP-targeted interventions are recommended.
Towards Selective Mycobacterial ClpP1P2 Inhibitors with Reduced Activity against the Human Proteasome
Authors: Moreira Wilfried , Santhanakrishnan Sridhar , Ngan Grace J. Y. , Low Choon Bing , Sangthongpitag Kanda , Poulsen Anders , Dymock Brian W. , Dick Thomas
Published: February 2017

Mycobacterium tuberculosis
is responsible for the greatest number of deaths worldwide due to a bacterial agent. We recently identified bortezomib (Velcade; compound 1) as a promising antituberculosis (anti-TB) compound. We showed that compound 1 inhibits the mycobacterial caseinolytic proteases P1 and P2 (ClpP1P2) and exhibits bactericidal activity, and we established compound 1 and ClpP1P2 as an attractive lead/target couple. However, compound 1 is a human-proteasome inhibitor currently approved for cancer therapy and, as such, exhibits significant toxicity. Selective inhibition of the bacterial protease over the human proteasome is desirable in order to maintain antibacterial activity while reducing toxicity. We made use of structural data in order to design a series of dipeptidyl-boronate derivatives of compound 1. We tested these derivatives for whole-cell ClpP1P2 and human-proteasome inhibition as well as bacterial-growth inhibition and identified compounds that were up to 100-fold-less active against the human proteasome but that retained ClpP1P2 and mycobacterial-growth inhibition as well as bactericidal potency. The lead compound, compound 58, had low micromolar ClpP1P2 and anti-
M. tuberculosis
activity, good aqueous solubility, no cytochrome P450 liabilities, moderate plasma protein binding, and low toxicity in two human liver cell lines, and despite high clearance in microsomes, this compound was only moderately cleared when administered intravenously or orally to mice. Higher-dose oral pharmacokinetics indicated good dose linearity. Furthermore, compound 58 was inhibitory to only 11% of a panel of 62 proteases. Our work suggests that selectivity over the human proteasome can be achieved with a drug-like template while retaining potency against ClpP1P2 and, crucially, anti-
M. tuberculosis
activity.
Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections
Authors: Shah Ansal , Justo Julie Ann , Bookstaver P. Brandon , Kohn Joseph , Albrecht Helmut , Al-Hasan Majdi N.
Published: February 2017

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to
Escherichia coli
. Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8;
P
< 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4;
P
< 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.
Prevalence and Molecular Characterization of
mcr-1
-Positive Salmonella Strains Recovered from Clinical Specimens in China
Authors: Cui Mingquan , Zhang Jinfei , Gu Zhen , Li Ruichao , Chan Edward Wai-chi , Yan Meiyin , Wu Congming , Xu Xuebin , Chen Sheng
Published: February 2017

The recently discovered colistin resistance element,
mcr-1
, adds to the list of antimicrobial resistance genes that rapidly erode the antimicrobial efficacy of not only the commonly used antibiotics but also the last-line agents of carbapenems and colistin. This study investigated the prevalence of the mobile colistin resistance determinant
mcr-1
in
Salmonella
strains recovered from clinical settings in China and the transmission potential of
mcr-1
-bearing mobile elements harbored by such isolates. The
mcr-1
gene was recoverable in 1.4% of clinical isolates tested, with the majority of them belonging to
Salmonella enterica
serotype Typhimurium. These isolates exhibited diverse pulsed-field gel electrophoresis (PFGE) profiles and high resistance to antibiotics other than colistin and particularly to cephalosporins. Plasmid analysis showed that
mcr-1
was carried on a variety of plasmids with sizes ranging from ∼30 to ∼250 kb, among which there were conjugative plasmids of ∼30 kb, ∼60 kb, and ∼250 kb and nonconjugative plasmids of ∼140 kb, ∼180 kb, and ∼240 kb. Sequencing of representative
mcr-1
-carrying plasmids revealed that all conjugative plasmids belonged to the IncX4, IncI2, and IncHI2 types and were highly similar to the corresponding types of plasmids reported previously. Nonconjugative plasmids all belonged to the IncHI2 type, and the nontransferability of these plasmids was attributed to the loss of a region carrying partial or complete
tra
genes. Our data revealed that, similar to the situation in
Escherichia coli
,
mcr-1
transmission in
Salmonella
was accelerated by various plasmids, suggesting that transmission of
mcr-1
-carrying plasmids between different species of
Enterobacteriaceae
may be a common event.
A Redox-Responsive Transcription Factor Is Critical for Pathogenesis and Aerobic Growth of Listeria monocytogenes
Authors: Whiteley Aaron T. , Ruhland Brittany R. , Edrozo Mauna B. , Reniere Michelle L.
Published: February 2017

Bacterial pathogens have evolved sophisticated mechanisms to sense and adapt to redox stress in nature and within the host. However, deciphering the redox environment encountered by intracellular pathogens in the mammalian cytosol is challenging, and that environment remains poorly understood. In this study, we assessed the contributions of the two redox-responsive, Spx-family transcriptional regulators to the virulence of
Listeria monocytogenes
, a Gram-positive facultative intracellular pathogen. Spx-family proteins are highly conserved in
Firmicutes
, and the
L. monocytogenes
genome contains two paralogues,
spxA1
and
spxA2
. Here, we demonstrate that
spxA1
, but not
spxA2
, is required for the oxidative stress response and pathogenesis. SpxA1 function appeared to be conserved with the
Bacillus subtilis
homologue, and resistance to oxidative stress required the canonical CXXC redox-sensing motif. Remarkably,
spxA1
was essential for aerobic growth, demonstrating that
L. monocytogenes
SpxA1 likely regulates a distinct set of genes. Although the Δ
spxA1
mutant did not grow in the presence of oxygen in the laboratory, it was able to replicate in macrophages and colonize the spleens, but not the livers, of infected mice. These data suggest that the redox state of bacteria during infection differs significantly from that of bacteria growing
in vitro
. Further, the host cell cytosol may resemble an anaerobic environment, with tissue-specific variations in redox stress and oxygen concentration.
THE ADDED VALUE OF A MULTICOUNTRY NETWORK FOR PROMOTING ETHICAL AND REGULATORY STANDARDS IN CLINICAL TRIALS IN LOW- AND MIDDLE-INCOME COUNTRIES: THE EXPERIENCE OF THE ‘SWITCHING THE POLES NETWORK’
Authors: Ravinetto Raffaella , Tinto Halidou , Diro Ermias , Mahendrahata Yodi , Okebe Joseph , Rijal Suman , Garcia Coralith , Sundar Shyam , Ndayisaba Gilles , Sopheak Thai , Ngoduc Thang , Loen Harry Van , Jacobs Jan , D'Alessandro Umberto , Boelaert Marleen , Buvé Anne
Published: February 2017

Background

In 2008, we created the ‘Switching The Poles’ Clinical Research Network, by joining the forces of non-commercial clinical research groups in Benin, Burkina Faso, Cambodia, Cuba, the Democratic Republic of Congo, Ethiopia, India, Indonesia, Nepal, Peru, Rwanda, The Gambia and Vietnam. Our aim was to strengthen capacity to conduct non-commercial clinical trials that comply with ethical/regulatory standards.

Methods

Our capacity building initiatives were designed to directly benefit the implementation of clinical trials, including various EDCTP-sponsored projects, e.g. 4ABC (7 countries), PREGACT (4), Microbicide Safety Biomarkers (3) and Ring Plus (1). Our training, coaching and networking activities targeted young researchers from the South as well as research professionals who are traditionally ‘neglected’ in trainings, such as data managers and laboratory staff. There were several thematic packages: Good Clinical Practice (GCP), Good Clinical Laboratory Practice, data management (DM), monitoring, and informed consent.

Results

We developed a theoretical and practice-based GCP training that was adopted by WANETAM Plus in 2013, and a set of standardised DM procedures. Data managers used to working on their own, now benefit from an e-platform (admitnetwork.org) for collaboration and peer advice. We started coaching clinical monitors, for facilitating reciprocal monitoring schemes. We publicly spoke out about ethical issues, e.g. ethical review of externally-sponsored trials, voluntariness in informed consent in vulnerable populations, and provided recommendations to the International Conference of Harmonization in its revision of GCP Guidelines. The inclusion of partners from so many diverse countries and settings resulted in cross-fertilisation and mutual learning. The Networks' small size facilitated interpersonal collaboration.

Conclusions

Our experience shows that a relatively small, but focused international network provides an excellent platform for supporting young researchers across different professional disciplines and helps to strengthen capacity for clinical research. This approach has enabled partners in low- and middle-income countries to successfully conduct harmonised GCP-compliant clinical trials.
CYTOLOGICAL PROFILE OF RED BLOOD CELLS IN HIV-INFECTED PATIENTS: CASE OF THE DOUALA GENERAL HOSPITAL (CAMEROON)
Authors: Bidias Amel , Ndjonka Dieudonné , Olemba Clémence , Souleymanou Arabo
Published: February 2017

Background

Haematological abnormalities have been documented as strong independent predictors of morbidity and mortality in HIV-infected individuals. Those infected with HIV without antiretroviral treatment (ART) have a high prevalence of abnormal blood cells. HIV-1 induced dyserythropoiesis in conjunction with the effects of HIV-related inflammation and/or chronic immune activation. The objective of the study is to identify and characterise the different red cell morphological changes that occur during the evolution of HIV infection in patients according to clinical, biological and therapeutic variables.

Methods

A total of 232 patients infected by HIV were included in this cross-sectional and descriptive study conducted at the Douala General Hospital (Cameroon) from June to December 2015. All the patients were screened for red blood cells abnormalities. Blood samples were taken in EDTA tubes for full blood counts (FBC) and blood films. chi-square test was used to compare the variables, and the statistical significance level adopted was p-value under 0.05.

Results

Three quarters of patients in our study had abnormal quantitative or qualitative red blood cells, giving a prevalence of 77.5%. The mean value of haemoglobin was 11.9 g/dl with a prevalence of anemia at 61.2% for all participants. The main red blood cells abnormalities were the anisocytosis (43.1%), the anisochromia (34.5%), the macrocytosis (24.1%), the microcytosis (13.8%), the hypochromia (12.9%) and the poikilocytosis (12.5%). These abnormalities are statistically significant and are dependent on the severity of the anaemia the WHO clinical stage, the ART duration and the medication regime with all p< 0.05.

Conclusions

The frequency of cytological abnormalities of red blood cells is high during HIV infection and proportional to the severity of the anemia, the duration of antiretroviral therapy diet and its clinical evolution stage. We recommend that reading blood films is systematic of FBC prescription in the monitoring of HIV-infected patients.
CYP2B6 GENOTYPE BASED EFAVIRENZ DOSE RECOMMENDATIONS DURING RIFAMPICIN-BASED ANTITUBERCULOSIS CO-TREATMENT FOR A SUB-SAHARAN AFRICA POPULATION
Authors: Mukonzo Jackson , Kuteesa Ronald , Ogwal-Okeng Jasper , Gustafsson Lars L. , Owen Joel , Aklillu Eleni
Published: February 2017

Background

Pharmacogenetics is a major determinant of the EFV–rifampicin interaction during HIV-TB co-treatment. We assessed genetic factors that influence EFV PK, treatment outcomes and provide genotype-based EFV dose recommendations for adult TB-HIV-1 co-infected Ugandans receiving rifampicin based anti-tuberculosis co-treatment.

Methods

Steady state plasma EFV concentrations (n=1216) from 158 HIV-TB co-infected patients (76 females) treated with efavirenz/lamivudine/zidovidine and rifampicin-based TB treatment were analysed. Patient genotypes forCYP2B6(*6&*11),CYP3A5(*3,*6&*7) andABCB1c.4046A>G, baseline biochemistries and CD4 and viral load change from baseline were determined. A one-compartment population PK model with first-order absorption (NONMEMTM) was used to estimate genotype effects on EFV PK. Population genotype-frequency-based PK simulations predicted AUCs and trough concentrations were compared between the product label / known reference values and different dose simulations.

Results

Compared toCYP2B6*1/*1, EFV post-induction CL/F was 2.5 and 1.7 times higher inCYP2B6*6/*6 andCYP2B6*1*/6,respectively. A 23% increase in F1 was observed for the variant ABCB1 c.4046A>G. EFV mean AUC was significantly higher inCYP2B6*6/*6genotypes compared toCYP2B6*1/*1(p< 0.0001). Simulated AUCs for a 600 mg EFV dose were 1.2 and 2.4 times greater than the product label mean AUC for the Ugandan population in general andCYP2B6*6/*6genotypes, respectively. EFV daily doses of 450 mg and 250 mg for the general population andCYP2B6*6/*6genotypes respectively yielded simulated exposures that were comparable to the product label. Overall, only 8.9% patients had HIV RNA >40 copies/mL after 84 days of treatment.

Conclusions

During rifampicin co-treatment, daily doses of 450 mg and 250 mg might meet the EFV dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6 homozygous variants, respectively.
RELATIONSHIP OF HIV-HBV CO-INFECTION WITH CD4 CELL COUNT AND ALANINE TRANSAMINASE LEVELS IN ANTI-RETROVIRAL THERAPY-NAïVE PATIENTS
Authors: Musukuma Kalo , Chilengi Roma , Dambe Rosalia , Usadi Benjamin , Vinikoor Michael
Published: February 2017

Background

In sub-Saharan Africa, the prevalence of hepatitis B virus (HBV) is between 6–20%. In Zambia, prevalence of HIV and HBV co-infection has been reported to be between 7.1% and 31.1%. Patients infected with HBV are at increased risk of experiencing elevated alanine transaminase enzyme (ALT) and HIV-HBV co-infection may lead to further reduced CD4 cell count before initiating antiretroviral therapy (ART). We investigated the relation of HBV with CD4 cell count and ALT enzyme in HIV-positive antiretroviral therapy-naïve patients.

Methods

This was a cross-sectional study conducted in 15 government clinics in Lusaka. There were 5436 adult patients who initiated antiretroviral therapy between 2011 and 2013. Cases were described as HIV-positive patients who tested HBsAg-positive and controls as HIV-positive patients who tested HBsAg-negative. HIV-HBV co-infection was defined as the number of patients who tested HBsAg-positive divided by the total tested (with 95% CI). Laboratory measures of CD4 and ALT were categorised in the analysis. Elevated ALT was defined as ALT≥66 IU/ml. CD4 cell count was dichotomised CD4 of >200 cells/µl.

Results

The median age was 35 (29–41) years. The median CD4 cell count was 202 (102–305) cells/µl with the median ALT being 20 (14–30) IU/ml. HIV−HBV prevalence was 12.3% (95% CI: 11.4−13.1). Elevated ALT was reported in 11.1% cases and 4.7% in controls (p-value <0.001). The adjusted odds ratio (OR) of experiencing elevated ALT before ART initiation for HI-HBV patients was 2.4 (95% CI: 1.8−3.2) compared to their HIV-mono-infected counterparts. Of the cases, 53.5% had a CD4<200 while only 48.9% of controls had CD4 <200 before ART initiation (p-value 0.026).

Conclusions

Prevalence of HBV is high among HIV-infected persons in Zambia. There is need to explore the interactions of these co-infections and their impact on CD4 cell count and ALT.
GENOTYPIC DIVERSITY AND DRUG SUSCEPTIBILITY PATTERNS AMONGM. TUBERCULOSISCOMPLEX ISOLATES RESPONSIBLE OF EXTRAPULMONARY TUBERCULOSIS IN CAMEROON FROM 2006–2015
Authors: Ngom Justice Trésor , Koro Francioli , Godwe Celestin , Adande Clemence , Ateugieu Romaric , Onana Tatiana , Ngono Annie , Kamdem Yannick , Ngo-Niobe Sara , Etoa François-Xavier
Published: February 2017

Background

Extrapulmonary tuberculosis can cause major irreversible health complications if it is diagnosed late and not well treated. In Cameroon, it remains neglected with very few data concerning its different forms, causing species and their drug susceptibility, while these data may help to understand the global epidemiology of tuberculosis in Cameroon.

Methods

We have made a retrospective study on 215 clinical isolates stored in Centre Pasteur of Cameroon. Isolates were genotyped using spoligotyping to identify lineages and families, and the drug susceptibility patterns were determined through proportion method.

Results

The primary resistance rate of isolates was 12.5%, among which 3.12% were mono-resistant to isoniazid, 1.56% to rifampicin and 3.9% to streptomycin. No mono-resistance was recorded for ethambutol. Multidrug-resistance rate to at least isoniazid and rifampicin was 3.12%. Spoligotyping revealed that 97.67% (210/215) and 2.32% (5/215) of extrapulmonary tuberculosis was caused byMycobacterium tuberculosisand ofM. africanum,respectively. M. boviswas absent. Spoligotyping lineages identified among theM. tuberculosiscomplex (MTC) showed a dominance of Cameroon family (40.46%). The other families were the ubiquitous T (36.27%), Haarlem (13.95%), U (6.04%) and LAM (1.39%). Ten spoligotypes had no SIT numbers. OnlyM. tuberculosisstrains were associated to resistance. But there was no significant difference for drug resistance between MTC lineages.

Conclusions

To the best of our knowledge, this study is the first to give the population structure of MTC strains causing extrapulmonary tuberculosis (ETB) and their drug susceptibilities. That shows the predominance ofM. tuberculosisspecies and the very low contribution ofM. africanumandM. bovisas the causative agent of ETB. It also shows that the population structure of this MTC is similar to that observed in pulmonary tuberculosis suggesting the dissemination of the pulmonary tuberculosis.