bluuebunny/crossref_metadata_2025 huggingface dataset:
Shaped Seamless Woven Garments
Authors: Seyam Abdel-Fattah M. , Saleh Sanaa S. , Sharkas Mamdouh Y. , AbouHashish Heba Z.
Published: March 2016

A range of intricate finished seamless shaped garments have been developed with the aim to fit predetermined sizes. The shape is created by using woven tubular fabrics with differential shrinkage in the same garment. The differential shrinkage is obtained by altering the fabric construction parameters at strategic locations along the length of the garment. The construction arameters include different weaves (plain, 2/2 basket, 1/3 twill, 2/2 twill, and crowfoot), weft densities, weft yarn counts, and weft yarns with different shrinkages (cotton, cotton that contains spandex, and cotton/polyester yarns). The weft yarn tension is used as an additional parameter to influence fabric shrinkage. A total of thirty-three woven fabrics are formed to establish the relationship between the construction parameters, weft tension, and shrinkage of the finished woven fabric. The relationship is used to produce a range of intricate garments with inherent shapes and predetermined sizes.
Preparation and Characterization of Methylcellulose Derivatives from Cellulosic Wastes
Authors: Haggag K. , El-Sayad H. S. , El-Moez Sh. Abd , El-Thalouth I. Abd
Published: March 2016

Cellulosic wastes from El-Nasr Co. for Intermediate Chemicals are used as a starting material for the preparation of methylcellulose with tailored properties. The wastes are first purified, followed by alkali ageing for different intervals of time. This is done to control the molecular weight of the cellulose molecules, thereby obtaining cellulosics with different degrees of polymerization (DP). These samples along with the original purified cellulose are methylated under similar conditions and the obtained methylcellulose samples are examined for solubility, degree of substitution (DS) and rheological properties. The results obtained from these investigations are summarized as follows. It is found that the DP of the starting cellulose progressively decreases by prolonging the duration of alkali ageing, while the carboxyl content increases. The DS of the methyl groups increases as the DP of the starting substrate decreases. The rheological properties as well as the apparent viscosity at various rates of shear for the prepared derivatives are thoroughly investigated.
Factors Contributing to Absorbency Behaviour of Pile Fabrics
Authors: Behera B.K. , Singh J.P.
Published: March 2016

The objective of this research paper is to investigate the important factors that contribute to the absorbency characteristics of terry fabric in order to produce highly absorbent terry towels by using suitable raw materials and changing the fabric constructional parameters. Yarns produced from two varieties of cotton (100% J-34 and MCU-5) and their blends with bamboo and poly vinyl alcohol (PVA) with different counts, twist and number of plies are used to prepare terry fabric of varying loop densities, loop lengths and loop shape factors. The water absorption rate and the total amount of water absorbed are measured by a gravimetric absorbency testing system (GATS). It is found that loop density is the most important parameter for water absorption rate followed by loop length and yarn twist. For the total amount of water absorbed, loop density is again the most important parameter followed by yarn twist, loop shape factor and number of ply in the pile yarn. Furthermore, a Box-Behnken statistical design with 3 factors and 3 levels is used to determine the optimum construction parameters to obtain the desired absorbency characteristics of terry towels and also to see the interaction effect of the various factors.
Antecedents and Consequences of Fashion Consciousness: An Empirical Study in Hong Kong
Authors: Lam Yuki W.K. , Yee Rachel W.Y.
Published: March 2016

Over the years, it has been without doubt that appearance consciousness is the privilege of women. In the past two decades, gender has become equivocal due to the diffusion of sexual boundaries. This has induced changes in male consciousness on fashion. However, there has been limited research that investigates the antecedents and consequences of fashion consciousness. This research aims to explore the potential factors that influence fashion consciousness and their impacts on the buying intention and behavior of men. We have conducted an empirical study on Generation Y male fashion consumers in Hong Kong. Our findings show that advancement of information technology, self-identity ambiguity, changing work practices of men, and media influence are four key factors that affect male fashion consciousness. Our results also reveal that fashion consciousness has a positive impact on the buying intention and behaviors of men. We recommend that fashion retailers allocate organizational resources on advertising and promotions to attract the interest of men towards their products
Threadless seaming - Application of Ultrasonic Technology in Fashion
Authors: Seram Niromi , Cabon Darron
Published: March 2016

Fashion is something beyond a normal approach with no limits to the permutations that one can think in terms of designing. Fashion, which represents the innovations of designers, brings forth revolution to the fashion world. The development of new technologies that are then applied to fashion offer opportunities for the industry to adapt to the multiple and ever changing lifestyles that redefine how we think about a design, and the manufacture and consumption of fashion. In the fashion world, not only designers but also scientists are experimenting and exploring with new ways to replace the traditional methods of garment construction with the use of sewing machines, and needle and thread. This paper will produce strong evidence to support the use of ultrasonic technology as an alternative for seaming.
Towards a positive youth justice
Authors: Byrne Ben , Case Stephen
Published: March 2016

Purpose

– The purpose of this paper is to consider and explore the principles that should inform a positive and progressive approach to conceptualising and delivering youth justice.

Design/methodology/approach

– Critical literature review, incorporating primary research and evaluation conducted by the authors.

Findings

– A children first model of positive youth justice should cohere around the promotion of four key principles: children’s rights and adults’ responsibilities; desistance and inclusion; diversion and systems management; relationship-based partnerships between children and practitioners.

Practical implications

– The child-friendly, child-appropriate and legitimacy-focused nature of the Children first, offender second (CFOS) model can encourage diversion from formal system contact, can enhance levels of participation and engagement with formal youth justice interventions and promotes positive behaviours and outcomes for children in trouble.

Originality/value

– The principles outlined progress youth justice into positive forms antithetical to the negative elements of the “new youth justice” and will have relevance to other jurisdictions, rooted as they are in universality, child development and children’s rights.
Sex offender registration and notification laws: thoughts from registered sex offenders in three states
Authors: Bowen Kendra , Frenzel Erika , Spraitz Jason D.
Published: March 2016

Purpose

– In the USA, sex offender policy research has focussed on demographic characteristics of registrants, recidivism rates of registrants, accuracy and completeness of listed information, and the collateral consequences experienced by registrants. This growing body of research demonstrates the need to explore offender perceptions of sex offender registration and notification (SORN) laws. The purpose of this paper is to assess whether registration related variables influenced sex offenders’ opinions about the registry, compliance with the registry, self-worth, and deterrence perceptions.

Design/methodology/approach

– This paper utilized a sample of 286 male registered sex offenders (RSO) in Pennsylvania, Texas, and Wisconsin. Four multivariate regression models were run to examine registration related variables impact on sex offender opinions of the registry, registry compliance, feelings of self-worth, and perceptions of deterrence.

Findings

– The multivariate regression results suggest registration related variables have a significant impact on RSO opinion of the registry, compliance with the registry, and opinions of self. Specifically, the number of collateral consequences that one experienced, police contacts that RSOs had, and being recognized as a sex offender were significantly related to the dependent variables in the regression models.

Originality/value

– This study adds to the body of research that indicates sex offenders experience a myriad of consequences that are outside the scope of the registered sex offender laws. Policy implications and societal consequences of these findings are discussed, as well as a future research agenda.
Theory and experimental research for the double ended tuning fork in MEMS
Authors: Guo Zhanshe , Li Boyu , Gao Yanshuai , Cheng Fucheng , Cao Le
Published: April 2016

Purpose

Being the key sensitive elements of the micro-electromechanical systems (MEMS) resonant sensors, performance of the double-ended tuning fork (DETF) will affect precision of the whole sensor greatly. Currently, most of the research on DETF is concentrated on ideal theory or simply mentioned as part of the sensor. But, in most engineering occasions, there exists many factors such as the additional mass, air damping and fabrication process, etc. However, few references are individually aimed at the mechanical characters of DETF. To choose the suitable DETF, it is important to solely research and measure the performance of this element.

Design/methodology/approach

In this paper, the authors combine the practical engineering applications and deduce the calculation method of sensitive element’s resonant frequency under various circumstances. The authors also design a force-generating system to make the loading simulation and verify the correctness of theory.

Findings

On the basis of Euler–Bernoulli theory and Rayleigh’s equation, frequency theories of DETF under four different situations have been deduced. A force-generating device is designed and fabricated to measure the mechanical characters of the DETF. The experiments using force-generating system, DETF, the high performance laser vibrometer and oscillograph are carried out. It verifies the correctness of theory.

Originality/value

Currently, most of the research on DETF is concentrated on ideal theory or simply mentioned as part of the sensor, and few references are individually aimed at the mechanical characters of DETF. Combining the practical engineering applications, the authors deduced the frequency theories of DETF. A force-generating system is designed and fabricated to measure the mechanical characters of the DETF, and the experiment results match the theoretical results very well.
Use of selective serotonin reuptake inhibitors reduces fertility in men
Authors: Nørr L. , Bennedsen B. , Fedder J. , Larsen E. R.
Published: March 2016

Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included. Use of SSRIs negatively affects semen parameters in most studies. In some studies, SSRIs are also shown to reduce DNA integrity. SSRIs can also delay ejaculation. Depression and anxiety can cause reduced libido, erectile dysfunction and delayed ejaculation as well. The use of SSRIs seems to reduce male fertility by affecting semen parameters, although most studies have a degree of confounding by indication caused by the underlying depression.
Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets
Authors: Shibata Hiroko , Yoshida Hiroyuki , Izutsu Ken-Ichi , Goda Yukihiro
Published: March 2016

Objectives

The aim of this study was to assess the effects of buffer systems (bicarbonate or phosphate at different concentrations) on the in vitro dissolution profiles of commercially available enteric-coated tablets.

Methods

In vitro dissolution tests were conducted using an USP apparatus II on 12 enteric-coated omeprazole and rabeprazole tablets, including innovator and generic formulations in phosphate buffers, bicarbonate buffers and a media modified Hanks (mHanks) buffer.

Key findings

Both omeprazole and rabeprazole tablets showed similar dissolution profiles among products in the compendial phosphate buffer system. However, there were large differences between products in dissolution lag time in mHanks buffer and bicarbonate buffers. All formulations showed longer dissolution lag times at lower concentrations of bicarbonate or phosphate buffers. The dissolution rank order of each formulation differed between mHanks buffer and bicarbonate buffers. A rabeprazole formulation coated with a methacrylic acid copolymer showed the shortest lag time in the high concentration bicarbonate buffer, suggesting varied responses depending on the coating layer and buffer components.

Conclusion

Use of multiple dissolution media during in vitro testing, including high concentration bicarbonate buffer, would contribute to the efficient design of enteric-coated drug formulations.
Assessment of transfusion utilization and patient outcomes at the largest referral and university hospital in Addis Ababa, Ethiopia
Authors: Tamene M. , Tsegaye A. , Birhanu A. , Taye B. , Birhaneselassie M.
Published: March 2016

Background

Assessment of blood and blood component utilization is an important tool to reduce inappropriate transfusions and to identify the frequency of blood and blood component utilization. However, in Ethiopia, the regular audit and assessment of transfusion practice is not routinely performed.

Objective

To characterize blood transfusion practices and monitor blood expiry and patient improvement status as an outcome at Black Lion Specialized Hospital (BLSH), Addis Ababa, Ethiopia.

Methods

A 1‐year hospital‐based audit was conducted to analyse utilization of blood components and patient outcomes at the Black Lion Specialized Hospital blood transfusion service. The study was conducted between October 2010 and January 2011 on data of patients transfused from September 2009 to August 2010. Information on blood and blood component utilization was collected from the blood bank log book on 373 subjects. Data were analysed for descriptive statistics and univariate and multivariate analyses using SPSS version 15.0 (SPSS INC., Chicago, IL, USA).

Results

Of 361 transfused study subjects, 856 units of blood were transfused with the mean of 2·37 units per recipient. Whole blood was most commonly transfused to 307 (85%) patients, and the combination of two blood products was administered to 27 (7·5%) patients. Plasma was transfused only for a single patient (0·3%). For patients who did not clinically improve, 45 (66·2%) were those transfused with whole blood. Significant associations were found between the overall improvement status of patients with the health professional who ordered the transfusion and the type of blood and blood product administered.

Conclusion

Transfusion of blood components was very low, and there was a high rate of whole blood transfusions. When component therapy was used, the rate of patient improvement status after transfusion was high. Therefore, blood transfusion service programmes in Ethiopia should focus on component transfusion and the need to strengthen guidelines for the appropriate use of blood and blood components as clinical therapy.
CLIMATE CHANGE AND ROAD SAFETY: A REVIEW TO ASSESS IMPACTS IN MALAYSIA
Authors: Shahid Shamsuddin , Minhans Anil
Published: March 2016

Climate change is very likely to cause a sharp increase in temperature, which in turn is likely to affect atmospheric water storage, and thereby the magnitudes, frequencies and intensities of rainfall. The road environment, including the weather factors is one of the major causes of accident across the world. Therefore, it is very certain that climate change induced changes in weather factors will affect road safety, if proper adaptation measures are not taken. The major objective of this article is to review the existing literatures on the influence of climatic variables on road accident in order to assess the possible impacts of climate change on road safety in Malaysia. The analysis of exiting literatures reveals that most imminent and certain impacts of climate change on road safety will be due to increase of temperature and rainfall related extremes. However, the impacts may not be very high in Malaysia due to moderate changes of those extremes over a long time. Any potential risk would be possible to mitigate by educating the people on possible impacts of climatic extremes on road environment and motivating them to change their driving behaviour during extreme weather events.
DETERMINATION OF GROOVE AND MECHANICAL PROPERTIES OF UNDERSIDE SHAPED CONCRETE PAVER
Authors: Mohamed Azman , A.Khalid Nur Hafizah , Md Nor Hasanan , Hainin Mohd Rosli , Jaya Ramadhansyah Putra , Mohd Sam Abdul Rahman , Ismail Che Ros
Published: March 2016

This paper presents an innovative paver with groove beneath the normal rectangular paver, named as the Underside Shaped Concrete Paver (USCP). A known fact, there is less friction between surface at beneath of paver and bedding sand. Therefore, USCP provide their own grip to bedding sand especially during compaction process. The process of groove determination was first performed before the USCP were tested for compression and flexural strength. The groove was determined based on the theory of bending stress. Combined with several factors, the basic groove shapes chosen were rectangular and triangular. Results indicated that some groove shapes are better in compression, but have weak flexural strength and vice versa. In fact, the relationship between mechanical properties and groove shape is indisputable. It is hoped that the outcomes can be considered in the future to design desirable paver.
CHARACTERIZATION OF THE PERFORMANCE OF ALUMINUM OXIDE NANOPARTICLES MODIFIED ASPHALT BINDER
Authors: Albrka Ali Shaban Imael , Ismail Amiruddin , Md. Yusoff Nur Izzi , Abdul Hassan Norhidayah , Ibrahim Ahmad Nazrul Hakimi
Published: March 2016

This study investigates the physical and rheological properties of asphalt binders modified by nano aluminum oxide (AL2O3). Several conventional tests were conducted, including penetration, softening point and ductility, rotational viscosity and dynamic shear rheometer (DSR). Based on the results of the tests, it was found that the hardness of modified asphalt binders increased with the addition of nano AL2O3 up to 5%. As a result of the increased hardness, the softening point of modified asphalt improved compared with base asphalt binders. The rheological property of modified binders was enhanced at low and high temperatures. The results of a DSR test revealed that the G* were improved, whereas the δ decreased slightly. The addition of a different percentage of AL2O3 to base binder had a remarkable influence on resistance to permanent deformation (high temperature rutting and low temperature fatigue). Results recognize 5 wt.% as the optimum content of the modifier. Therefore, nano AL2O3 can be considered as a proper alternative additive to modify the properties of asphalt cement.
Optimizing a Functionally Graded Metal-Matrix Heat Sink Through Growth of a Constructal Tree of Convective Fins
Authors: Kephart Jacob , Jones G. F.
Published: March 2016

Optimal material utilization in metal-matrix heat sink is investigated using constructal design (CD) in combination with fin theory to develop a constructal tree of optimally shaped convective fins. The structure is developed through systematic growth of constructs, consisting initially of a single convective fin enveloped in a convective medium. Increasingly complex convective fin structures are created and optimized at each level of complexity to determine optimal fin shapes, aspect ratios, and fin-base thickness ratios. One result of the optimized structures is a functional grading of porosity. The porosity increases as a function of distance from the heated surface in a manner ranging from linear to a power function of distance with exponent of about 2. The degree of nonlinearity in this distribution varies depending on the volume of the heat sink and average packing density and approaches a parabolic shape for large volume. For small volume, porosity approaches a linear function of distance. Thus, a parabolic (or least-material) fin shape at each construct level would not necessarily be optimal. Significant improvements in total heat transfer, up to 55% for the cases considered in this work, were observed when the fin shape is part of the optimization in a constructal tree of convective fins. The results of this work will lead to better understanding of the role played by the porosity distribution in a metal-matrix heat sink and may be applied to the analysis, optimization, and design of more effective heat sinks for electronics cooling and related areas.
Simulation of Deep Surge in a Turbocharger Compression System
Authors: Dehner Rick , Selamet Ahmet , Keller Philip , Becker Michael
Published: April 2016

Large-amplitude deep surge instabilities are studied in a turbocharger compression system with a one-dimensional (1D) engine simulation code. The system consists of an upstream compressor duct open to ambient, a centrifugal compressor, a downstream compressor duct, a large plenum, and a throttle valve exhausting to ambient. As the compressor mass flow rate is reduced below the peak pressure ratio for a given speed, mild surge oscillations occur at the Helmholtz resonance of the system, and a further reduction in flow rate results in deep surge considerably below the Helmholtz resonance. At the boundary with mild surge, the deep surge cycles exhibit, for the particular system considered, a long cycle period containing four distinct flow phases, including quiet (stable), instability growth (mild surge), blowdown (reversal), and recovery. Further reductions in flow rate decrease the deep surge cycle period, eliminate the quiet flow phase, and shorten the duration of the instability growth phase. Simulated oscillations of nondimensional flow rate, pressure, and speed parameters show good agreement with the experimental results available in literature, in terms of deep surge cycle flow phases along with the amplitude and frequency of the resulting fluctuations. The predictions illustrate that the quiet and instability growth phases, exhibited by this compression system, disappear as the plenum volume is substantially reduced.
Modeling the voice source in terms of spectral slopes
Authors: Garellek Marc , Samlan Robin , Gerratt Bruce R. , Kreiman Jody
Published: March 2016

A psychoacoustic model of the voice source spectrum is proposed. The model is characterized by four spectral slope parameters: the difference in amplitude between the first two harmonics (H1–H2), the second and fourth harmonics (H2–H4), the fourth harmonic and the harmonic nearest 2 kHz in frequency (H4–2 kHz), and the harmonic nearest 2 kHz and that nearest 5 kHz (2 kHz–5 kHz). As a step toward model validation, experiments were conducted to establish the acoustic and perceptual independence of these parameters. In experiment 1, the model was fit to a large number of voice sources. Results showed that parameters are predictable from one another, but that these relationships are due to overall spectral roll-off. Two additional experiments addressed the perceptual independence of the source parameters. Listener sensitivity to H1–H2, H2–H4, and H4–2 kHz did not change as a function of the slope of an adjacent component, suggesting that sensitivity to these components is robust. Listener sensitivity to changes in spectral slope from 2 kHz to 5 kHz depended on complex interactions between spectral slope, spectral noise levels, and H4–2 kHz. It is concluded that the four parameters represent non-redundant acoustic and perceptual aspects of voice quality.
Cause-effect relationship between vocal fold physiology and voice production in a three-dimensional phonation model
Authors: Zhang Zhaoyan
Published: April 2016

The goal of this study is to better understand the cause-effect relation between vocal fold physiology and the resulting vibration pattern and voice acoustics. Using a three-dimensional continuum model of phonation, the effects of changes in vocal fold stiffness, medial surface thickness in the vertical direction, resting glottal opening, and subglottal pressure on vocal fold vibration and different acoustic measures are investigated. The results show that the medial surface thickness has dominant effects on the vertical phase difference between the upper and lower margins of the medial surface, closed quotient, H1-H2, and higher-order harmonics excitation. The main effects of vocal fold approximation or decreasing resting glottal opening are to lower the phonation threshold pressure, reduce noise production, and increase the fundamental frequency. Increasing subglottal pressure is primarily responsible for vocal intensity increase but also leads to significant increase in noise production and an increased fundamental frequency. Increasing AP stiffness significantly increases the fundamental frequency and slightly reduces noise production. The interaction among vocal fold thickness, stiffness, approximation, and subglottal pressure in the control of F0, vocal intensity, and voice quality is discussed.
A Cross-Sectional Study of the Relationship of Physical Activity with Depression and Cognitive Deficit in Older Adults
Authors: Paulo Thais R.S. , Tribess Sheilla , Sasaki Jeffer Eidi , Meneguci Joilson , Martins Cristiane A. , Freitas Ismael F. , Romo-Perez Vicente , Virtuoso Jair S.
Published: March 2016

The aim of this study was to examine the association of physical activity with depression and cognition deficit, separately and combined, in Brazilian older adults. We analyzed data from 622 older adults. Physical activity was assessed using the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale, while cognitive deficit was assessed using the Mini-Mental State Examination. Multinomial logistic regressions were used to assess associations of depression and cognitive deficit with sociodemographic, health, and behavioral variables. Prevalence of physical inactivity (< 150 min of moderate-to-vigorous physical activity/week), depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical inactivity was associated with depression (OR: 1.83, 95% CI: 1.14–2.94) and with depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01–8.91). Physically inactive participants were also more likely to present limitations in orientation and language functions. Physical inactivity was associated with depression and also with depression and cognitive deficit combined in older adults.
JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors
Authors: Gao Sizhi P. , Chang Qing , Mao Ninghui , Daly Laura A. , Vogel Robert , Chan Tyler , Liu Shu Hui , Bournazou Eirini , Schori Erez , Zhang Haiying , Red Brewer Monica , Pao William , Morris Luc , Ladanyi Marc , Arcila Maria , Manova-Todorova Katia , de Stanchina Elisa , Norton Larry , Levine Ross L. , Altan-Bonnet Gregoire , Solit David , Zinda Michael , Huszar Dennis , Lyden David , Bromberg Jacqueline F.
Published: March 2016

JAK2 inhibitors increase the abundance of EGFR in lung cancer cells, thereby restoring the efficacy of EGFR inhibitors in resistant tumors.
PLIF: A rapid, accurate method to detect and quantitatively assess protein-lipid interactions
Authors: Ceccato Laurie , Chicanne Gaëtan , Nahoum Virginie , Pons Véronique , Payrastre Bernard , Gaits-Iacovoni Frédérique , Viaud Julien
Published: March 2016

A fluorescence-based technique for detecting protein-lipid interactions may aid development of drugs that disrupt these regulatory interactions.
Papers of note in
Science
Authors: Gough Nancy R.
Published: March 2016

This week’s articles highlight how disruption of gene neighborhoods contributes to cancer, the development of tumor neoantigens, and the evolution and visualization of transcriptional regulation.
PP2A to Alzheimer’s rescue
Authors: Prabakaran Sudhakaran , Gough Nancy R.
Published: March 2016

Transgenic mice with altered methylation of PP2A reveal a new strategy for treating Alzheimer’s disease.
Making cancer cells dependent on EGFR
Authors: Ferrarelli Leslie K.
Published: March 2016

Counterintuitively, alleviating negative regulation of EGFRs sensitizes cells to EGFR inhibition.
Papers of note in
Science Translational Medicine
Authors: Ferrarelli Leslie K.
Published: March 2016

This week’s articles describe new therapeutic targets in the signaling pathways underlying inflammatory diseases.
Activity of Fusidic Acid Tested against Staphylococci Isolated from Patients in U.S. Medical Centers in 2014
Authors: Farrell David J. , Mendes Rodrigo E. , Castanheira Mariana , Jones Ronald N.
Published: March 2016

Fusidic acid (FA) activity was evaluated against 2,002 clinical staphylococcal isolates collected in U.S. hospitals during 2014. FA (MIC
50/90
, 0.12/0.12 μg/ml) inhibited 99.8% of
Staphylococcus aureus
isolates at ≤1 μg/ml. Only four
S. aureus
isolates displayed FA values of >2 μg/ml (three strains with
fusC
and one with an L461K substitution in
fusA
), and they were isolated from patients in four states. In conclusion, FA demonstrated sustained, potent activity against this recent collection of U.S. staphylococci.
A Replicative
In Vitro
Assay for Drug Discovery against Leishmania donovani
Authors: Tegazzini Diana , Díaz Rosario , Aguilar Fernando , Peña Imanol , Presa Jesús L. , Yardley Vanessa , Martin Julio J. , Coteron Jose M. , Croft Simon L. , Cantizani Juan
Published: March 2016

The protozoan parasite
Leishmania donovani
is the causative agent of visceral leishmaniasis, a disease potentially fatal if not treated. Current available treatments have major limitations, and new and safer drugs are urgently needed. In recent years, advances in high-throughput screening technologies have enabled the screening of millions of compounds to identify new antileishmanial agents. However, most of the compounds identified
in vitro
did not translate their activities when tested in
in vivo
models, highlighting the need to develop more predictive
in vitro
assays. In the present work, we describe the development of a robust replicative, high-content,
in vitro
intracellular
L. donovani
assay. Horse serum was included in the assay media to replace standard fetal bovine serum, to completely eliminate the extracellular parasites derived from the infection process. A novel phenotypic
in vitro
infection model has been developed, complemented with the identification of the proliferation of intracellular amastigotes measured by EdU incorporation.
In vitro
and
in vivo
results for miltefosine, amphotericin B, and the selected compound 1 have been included to validate the assay.
Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp
Authors: da Silva Anderson Ramos , de Andrade Neto João Batista , da Silva Cecília Rocha , Campos Rosana de Sousa , Costa Silva Rose Anny , Freitas Daniel Domingues , do Nascimento Francisca Bruna Stefany Aires , de Andrade Larissa Nara Dantas , Sampaio Letícia Serpa , Grangeiro Thalles Barbosa , Magalhães Hemerson Iury Ferreira , Cavalcanti Bruno Coêlho , de Moraes Manoel Odorico , Nobre Júnior Hélio Vitoriano
Published: March 2016

The incidence of fungal infections and, in particular, the incidence of fungal antibiotic resistance, which is associated with biofilm formation, have significantly increased, contributing to morbidity and mortality. Thus, new therapeutic strategies need to be developed. In this context, natural products have emerged as a major source of possible antifungal agents. Berberine is a protoberberine-type isoquinoline alkaloid isolated from the roots, rhizomes, and stem bark of natural herbs, such as
Berberis aquifolium
,
Berberis vulgaris
,
Berberis aristata
, and
Hydrastis canadensis
, and of
Phellodendron amurense
. Berberine has been proven to have broad antibacterial and antifungal activity. In the present study, the potential antifungal effect of berberine against fluconazole-resistant
Candida
and
Cryptococcus neoformans
strains, as well as against the biofilm form of
Candida
spp., was assessed. The antifungal effect of berberine was determined by a broth microdilution method (the M27-A3 method of the Clinical and Laboratory Standards Institute) and flow cytometry techniques, in which the probable mechanism of action of the compound was also assessed. For biofilm assessment, a colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the susceptibility of sessile cells. The isolates used in the study belonged to the Laboratory of Bioprospection and Experiments in Yeast (LABEL) of the Federal University of Ceará. After 24 and 72 h, fluconazole-resistant
Candida
and
Cryptococcus neoformans
strains showed berberine MICs equal to 8 μg/ml and 16 μg/ml, respectively. Cytometric analysis showed that treatment with berberine caused alterations to the integrity of the plasma and mitochondrial membranes and DNA damage, which led to cell death, probably by apoptosis. Assessment of biofilm-forming isolates after treatment showed statistically significant reductions in biofilm cell activity (
P
< 0.001).
Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans
Authors: Badrane Hassan , Nguyen M. Hong , Clancy Cornelius J.
Published: March 2016

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P
2
] activates the yeast cell wall integrity pathway.
Candida albicans
exposure to caspofungin results in the rapid redistribution of PI(4,5)P
2
and septins to plasma membrane foci and subsequent fungicidal effects. We studied
C. albicans
PI(4,5)P
2
and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5)P
2
and septins were visualized by live imaging of
C. albicans
cells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5)P
2
was also visualized in GFP-PH domain-expressing
C. albicans mkc1
mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5)P
2
and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5)P
2
levels increased in a dose-response manner at caspofungin concentrations of ≤4× MIC and progressively decreased at concentrations of ≥8× MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5)P
2
and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4× MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5)P
2
redistribution remained apparent in
mkc1
mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at ≤4× and ≥8× MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H
2
O
2
did not impact the PI(4,5)P
2
or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5)P
2
-septin and PKC-Mkc1 responses that correlate with the extent of
C. albicans
killing, and the responses are not induced by other antifungal agents. PI(4,5)P
2
-septin regulation is crucial in early caspofungin responses and PKC-Mkc1 activation.
The LABCG2 Transporter from the Protozoan Parasite Leishmania Is Involved in Antimony Resistance
Authors: Perea Ana , Manzano José Ignacio , Castanys Santiago , Gamarro Francisco
Published: March 2016

Treatment for leishmaniasis, which is caused by
Leishmania
protozoan parasites, currently relies on a reduced arsenal of drugs. However, the significant increase in the incidence of drug therapeutic failure and the growing resistance to first-line drugs like antimonials in some areas of Northern India and Nepal limit the control of this parasitic disease. Understanding the molecular mechanisms of resistance in
Leishmania
is now a matter of urgency to optimize drugs used and to identify novel drug targets to block or reverse resistant mechanisms. Some members of the family of ATP-binding cassette (ABC) transporters in
Leishmania
have been associated with drug resistance. In this study, we have focused our interest to characterize LABCG2's involvement in drug resistance in
Leishmania. Leishmania major
parasites overexpressing the ABC protein transporter LABCG2 were generated in order to assess how LABCG2 is involved in drug resistance. Assays of susceptibility to different leishmanicidal agents were carried out. Analysis of the drug resistance profile revealed that
Leishmania
parasites overexpressing LABCG2 were resistant to antimony, as they demonstrated a reduced accumulation of Sb
III
due to an increase in drug efflux. Additionally, LABCG2 was able to transport thiols in the presence of Sb
III
. Biotinylation assays using parasites expressing LABCG2 fused with an N-terminal green fluorescent protein tag revealed that LABCG2 is partially localized in the plasma membrane; this supports data from previous studies which suggested that LABCG2 is localized in intracellular vesicles that fuse with the plasma membrane during exocytosis. In conclusion,
Leishmania
LABCG2 probably confers antimony resistance by sequestering metal-thiol conjugates within vesicles and through further exocytosis by means of the parasite's flagellar pocket.
Rapid Flow Cytometry Test for Identification of Different Carbapenemases in Enterobacteriaceae
Authors: Silva Ana P. , Faria-Ramos Isabel , Ricardo Elisabete , Miranda Isabel M. , Espinar Maria J. , Costa-de-Oliveira Sofia , Cantón Rafael , Rodrigues Acácio G. , Pina-Vaz Cidália
Published: March 2016

A flow cytometry test was developed to identify carbapenemase production by
Enterobacteriaceae
and to discriminate between the different types of carbapenemases (classes A, B, and D). It is based on the detection of meropenem activity against bacteria, coupled with different carbapenemase inhibitors, which is assessed by flow cytometry. It represents a convenient, fast, and reliable approach (100% sensitivity and 100% specificity) for the detection and characterization of different carbapenemases.
Biofilm Production and Antibiofilm Activity of Echinocandins and Liposomal Amphotericin B in Echinocandin-Resistant Yeast Species
Authors: Marcos-Zambrano Laura Judith , Gómez-Perosanz Marta , Escribano Pilar , Zaragoza Oscar , Bouza Emilio , Guinea Jesús
Published: March 2016

The echinocandins and liposomal amphotericin B are active against biofilm produced by echinocandin-susceptible
Candida
strains. However, few data have been reported on the production of biofilm by echinocandin-resistant isolates and their antifungal susceptibility. We studied the production of biofilm by
fks
mutant
Candida
strains and intrinsically echinocandin-resistant non-
Candida
isolates and the susceptibility of both entities to liposomal amphotericin B and echinocandins. We analyzed the production of biofilm by isolates from patients with fungemia (
fks
mutant
Candida
,
n
= 5; intrinsically echinocandin-resistant non-
Candida
,
n
= 12; and
Candida
wild type,
n
= 10). Biofilm formation was measured to classify strains according to biomass (crystal violet assay) and metabolic activity (XTT reduction assay). Preformed biofilms were tested against liposomal amphotericin B, caspofungin, micafungin, and anidulafungin. The sessile MIC was defined as the antifungal concentration yielding a 50% or 80% reduction in the metabolic activity of the biofilm compared to that of the growth control (SMIC
50
and SMIC
80
, respectively).
fks
mutant
Candida
isolates formed biofilms in a fashion similar to that of
Candida
wild-type strains. The echinocandins had the highest activity against biofilms formed by wild-type
Candida
isolates, followed by
fks
mutant
Candida
isolates and non-
Candida
isolates. Liposomal amphotericin B had the highest activity against
fks
mutant
Candida
biofilms. The formation of biofilm by echinocandin-resistant strains was similar to that of wild-type strains, although resistance to echinocandins remained high.
Draft Genome Sequence of the Dimorphic Fungus
Sporothrix pallida
, a Nonpathogenic Species Belonging to
Sporothrix,
a Genus Containing Agents of Human and Feline Sporotrichosis
Authors: D'Alessandro Enrico , Giosa Domenico , Huang Lilin , Zhang Jing , Gao Wenchao , Brankovics Balazs , Oliveira Manoel Marques Evangelista , Scordino Fabio , Lo Passo Carla , Criseo Giuseppe , van Diepeningen Anne D. , Huang Huaiqiu , de Hoog G. Sybren , Romeo Orazio
Published: April 2016

Sporothrix pallida
is considered to be a mostly avirulent environmental fungus, phylogenetically closely related to the well-known pathogen
Sporothrix schenckii
. Here, we present the first assembly of its genome, which provides a valuable resource for future comparative genomic studies between nonpathogenic and pathogenic
Sporothrix
spp.
Whole-Genome Sequencing of Two Latin American–Mediterranean Extensively Drug-Resistant
Mycobacterium tuberculosis
Clinical Isolates from Medellín, Colombia
Authors: Alvarez N. , Haft D. , Hurtado U. A. , Robledo J. , Rouzaud F.
Published: April 2016

Colombia, with a tuberculosis incidence of 33 cases per 100,000 population, is one of the countries that have reported extensively drug-resistant 
Mycobacterium tuberculosis
 (XDR-TB). We report the high-quality draft genome sequences of two Latin American–Mediterranean XDR-TB clinical isolates (TBR-152 and TBR-175), comprising 4,303,775 bp and 4,330,115 bp, respectively.
Draft Genome Sequence of
Paenibacillus
sp. Strain DMB5, Acclimatized and Enriched for Catabolizing Anthropogenic Compounds
Authors: Johnson Jenny , Shah Binal , Jain Kunal , Parmar Nidhi , Hinsu Ankit , Patel Namrata , Joshi Chaitanya G. , Madamwar Datta
Published: April 2016

Here, we present the draft genome sequence of
Paenibacillus
sp. strain DMB5, isolated from polluted sediments of the Kharicut Canal, Vatva, India, having a genome size of 7.5 Mbp and 7,077 coding sequences. The genome of this dye-degrading bacterium provides valuable information on the microbe-mediated biodegradation of anthropogenic compounds.
Meningococcal Factor H Binding Protein Vaccine Antigens with Increased Thermal Stability and Decreased Binding of Human Factor H
Authors: Rossi Raffaella , Konar Monica , Beernink Peter T.
Published: March 2016

Neisseria meningitidis
causes cases of bacterial meningitis and sepsis. Factor H binding protein (FHbp) is a component of two licensed meningococcal serogroup B vaccines. FHbp recruits the complement regulator factor H (FH) to the bacterial surface, which inhibits the complement alternative pathway and promotes immune evasion. Binding of human FH impairs the protective antibody responses to FHbp, and mutation of FHbp to decrease binding of FH can increase the protective responses. In a previous study, we identified two amino acid substitutions in FHbp variant group 2 that increased its thermal stability by 21°C and stabilized epitopes recognized by protective monoclonal antibodies (MAbs). Our hypothesis was that combining substitutions to increase stability and decrease FH binding would increase protective antibody responses in the presence of human FH. In the present study, we generated four new FHbp single mutants that decreased FH binding and retained binding of anti-FHbp MAbs and immunogenicity in wild-type mice. From these mutants, we selected two, K219N and G220S, to combine with the stabilized double-mutant FHbp antigen. The two triple mutants decreased FH binding >200-fold, increased the thermal stability of the N-terminal domain by 21°C, and bound better to an anti-FHbp MAb than the wild-type FHbp. In human-FH-transgenic mice, the FHbp triple mutants elicited 8- to 15-fold-higher protective antibody responses than the wild-type FHbp antigen. Collectively, the data suggest that mutations to eliminate binding of human FH and to promote conformational stability act synergistically to optimize FHbp immunogenicity.
Single-Cell Analysis of the Dps Response to Oxidative Stress
Authors: De Martino Michela , Ershov Dmitry , van den Berg Peter J. , Tans Sander J. , Meyer Anne S.
Published: March 2016

Microorganisms have developed an elaborate spectrum of mechanisms to respond and adapt to environmental stress conditions. Among these is the expression of
dps
, coding for the
D
NA-binding
p
rotein from
s
tarved cells. Dps becomes the dominant nucleoid-organizing protein in stationary-phase
Escherichia coli
cells and is required for robust survival under stress conditions, including carbon or nitrogen starvation, oxidative stress, metal exposure, and irradiation. To study the complex regulation of Dps in
E. coli
, we utilized time-lapse fluorescence microscopy imaging to examine the kinetics, input encoding, and variability of the Dps response in single cells. In the presence of an oxidative stressor, we observed a single pulse of activation of Dps production. Increased concentrations of H
2
O
2
led to increased intensity and duration of the pulse. While lower concentrations of H
2
O
2
robustly activated the Dps response with little effect on the growth rate, higher concentrations of H
2
O
2
resulted in dramatically lower and highly varied growth rates. A comparison of cells exposed to the same concentration of H
2
O
2
revealed that increased levels of Dps expression did not confer a growth advantage, indicating that recovery from stress may rely primarily upon variation in the amount of damage caused to individual cells.

IMPORTANCE
We show for the first time the response of the DNA-binding protein from starved cells (Dps) to oxidative stress in single cells of
E. coli
. Through time-lapse fluorescence microscopy, a single pulse of Dps production is observed in cells exposed to H
2
O
2
, with a duration and intensity of induction proportional to the concentration of the applied stress. More intense Dps expression did not provide a growth benefit to the bacteria, suggesting that healing from oxidative stress may largely depend upon the amount of damage in each individual cell.