bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Series of Fluorescent Indicators for Super Acids
Authors: Shih I‐Chih , Yeh Yu‐Shan , Wu I‐Che , Chen You‐Hua , Shen Jiun‐Yi , Chen Yi‐An , Ho Mei‐Lin , Chou Pi‐Tai 
Published: August 2014

AbstractThe photophysical properties of fluorescent Hammett acidity indicator derived from 3,4,5,6‐tetrahydrobis(pyrido[3,2‐g]indolo)[2,3‐a:3′,2′‐j]acridine (1a), 6‐bis(pyrido[3,2‐g]indol‐2′‐yl)pyridine (1b) and their analogues have been investigated in sulfuric acid solutions by means of absorption, fluorimetry, relaxation dynamics and computational approach. These new indicators undergo a reversible protonation process in the Hammett acidity range of H0 < 0, accompanied by a drastic increase of the bright blue‐green (1a) or yellow (1b) fluorescence intensity upon increasing the acidity. For 1a in H2SO4, the emission yield increases as large as 200 folds from pH = −0.41 to the Hammett acidity range of −5.17, the results of which are rationalized by a much increase of the steric hindrance upon third protonation toward the central pyridinic site, together with their accompanied changes of electronic configuration from charge transfer to a delocalized ππ* character in the lowest lying excited state. The combination of 1a and 1b renders a wide and linear range of H0 measurement from −1.2 to −5.1 detected by highly intensive fluorescence.
Structural Analysis of a Small H-Darrieus Wind Turbine Using Beam
Models: Development and Assessment
Authors: Bianchini Alessandro , Cangioli Francesco , Papini Susanna , Rindi Andrea , Carnevale Ennio Antonio , Ferrari Lorenzo 
Published: August 2014

Abstract
In the present wind energy research, Darrieus-type vertical axis wind turbines (VAWTs) are increasingly appreciated, especially in small installations. In particular, H-shaped turbines can provide attractive spaces for novel design solutions, aimed at reducing the visual impact of the rotors and then at improving their degree of integration with several installation contexts (e.g., a built environment); moreover, novel small rotors are thought to be able in the near future to make large use also of new and cheaper materials (e.g., plastic or light alloys) which could notably reduce the final cost of the produced energy. As a consequence, the structural analysis of the rotors becomes more and more important: a continuous check between the design solutions needed to maximize the aerodynamic performance of the blades and the structural constraints must be provided. In addition, the requirements of international standards for certification encourage the development of proper numerical tools, possibly with low computational costs for the manufacturers. In this study, the structural analysis of a novel three-helix-bladed Darrieus turbine is presented; the turbine is a real industrial machine almost entirely produced with plastic with a new complex aesthetic design. In detail, a structural modeling based on beam elements has been developed and assessed in comparison to more complex models, as it was thought to provide a notable reduction of the computational cost of the simulations with an acceptable decrease of the accuracy. Moreover, the 1D structural model was exploited to verify the capabilities of a novel software, able to verify the dynamic response of the wind turbine in real functioning, i.e., with mechanical loads and interactions with the wind flow. Benefits and drawbacks of the proposed modeling approach are finally discussed by analyzing both the calculation time and the accuracy of the simulations.
Molecular Typing of Treponema pallidum in the Czech Republic during 2011 to 2013: Increased Prevalence of Identified Genotypes and of Isolates with Macrolide Resistance
Authors: Grillová Linda , Pĕtrošová Helena , Mikalová Lenka , Strnadel Radim , Dastychová Eliška , Kuklová Ivana , Kojanová Martina , Kreidlová Miluše , Vaňousová Daniela , Hercogová Jana , Procházka Přemysl , Zákoucká Hana , Krchňáková Alena , Vašků Vladimír , Šmajs David 
Published: August 2014

ABSTRACT

From January 2011 to December 2013, a total of 262 samples, from 188 patients suspected of having syphilis were tested for the presence of treponemal DNA by PCR amplification of five chromosomal loci, including the
polA
(TP0105),
tmpC
(TP0319), TP0136, TP0548, and 23S rRNA genes. Altogether, 146 samples from 103 patients were PCR positive for treponemal DNA. A set of 81 samples from 62 PCR-positive patients were typeable, and among them, nine different genotypes were identified. Compared to a previous study in the Czech Republic during 2004 to 2010, the number of genotypes detected among syphilis patients in a particular year increased to six in both 2012 and 2013, although they were not the same six. The proportion of macrolide-resistant clinical isolates in this 3-year study was 66.7%.
Genetic Relatedness versus Biological Compatibility between Aspergillus fumigatus and Related Species
Authors: Sugui Janyce A. , Peterson Stephen W. , Figat Abigail , Hansen Bryan , Samson Robert A. , Mellado Emilia , Cuenca-Estrella Manuel , Kwon-Chung Kyung J. 
Published: August 2014

ABSTRACT

Aspergillus
section
Fumigati
contains 12 clinically relevant species. Among these
Aspergillus
species,
A. fumigatus
is the most frequent agent of invasive aspergillosis, followed by
A. lentulus
and
A. viridinutans
. Genealogical concordance and mating experiments were performed to examine the relationship between phylogenetic distance and mating success in these three heterothallic species. Analyses of 19 isolates from section
Fumigati
revealed the presence of three previously unrecognized species within the broadly circumscribed species
A. viridinutans
. A single mating type was found in the new species
Aspergillus pseudofelis
and
Aspergillus pseudoviridinutans
, but in
Aspergillus parafelis
, both mating types were present. Reciprocal interspecific pairings of all species in the study showed that the only successful crosses occurred with the
MAT1-2
isolates of both
A. parafelis
and
A. pseudofelis
. The
MAT1-2
isolate of
A. parafelis
was fertile when paired with the
MAT1-1
isolates of
A. fumigatus
,
A. viridinutans
,
A. felis
,
A. pseudoviridinutans
, and
A. wyomingensis
but was not fertile with the
MAT1-1
isolate of
A. lentulus
. The
MAT1-2
isolates of
A. pseudofelis
were fertile when paired with the
MAT1-1
isolate of
A. felis
but not with any of the other species. The general infertility in the interspecies crossings suggests that genetically unrelated species are also biologically incompatible, with the
MAT1-2
isolates of
A. parafelis
and
A. pseudofelis
being the exception. Our findings underscore the importance of genealogical concordance analysis for species circumscription, as well as for accurate species identification, since misidentification of morphologically similar pathogens with differences in innate drug resistance may be of grave consequences for disease management.
Inhibition of the Human Respiratory Syncytial Virus Small Hydrophobic Protein and Structural Variations in a Bicelle Environment
Authors: Li Yan , To Janet , Verdià-Baguena Carmina , Dossena Silvia , Surya Wahyu , Huang Mei , Paulmichl Markus , Liu Ding Xiang , Aguilella Vicente M. , Torres Jaume 
Published: August 2014

ABSTRACT
The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report the first inhibitor of the SH protein channel, pyronin B, and we have mapped its binding site to a conserved surface of the RSV SH pentamer, at the C-terminal end of the transmembrane domain. The validity of the SH protein structural model used has been confirmed by using a bicellar membrane-mimicking environment. However, in bicelles the α-helical stretch of the TM domain extends up to His-51, and by comparison with previous models both His-22 and His-51 adopt an interhelical/lumenal orientation relative to the channel pore. Neither His residue was found to be essential for channel activity although His-51 protonation reduced channel activity at low pH, with His-22 adopting a more structural role. The latter results are in contrast with previous patch clamp data showing channel activation at low pH, which could not be reproduced in the present work. Overall, these results establish a solid ground for future drug development targeting this important viroporin.

IMPORTANCE
The human respiratory syncytial virus (hRSV) is responsible for 64 million reported cases of infection and 160,000 deaths each year. Lack of adequate antivirals fuels the search for new targets for treatment. The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by hRSV and other paramyxoviruses, and its absence leads to viral attenuation
in vivo
and early apoptosis in infected cells. SH protein forms pentameric ion channels that may constitute novel drug targets, but no inhibitor for this channel activity has been reported so far. A small-molecule inhibitor, pyronin B, can reduce SH channel activity, and its likely binding site on the SH protein channel has been identified. Black lipid membrane (BLM) experiments confirm that protonation of both histidine residues reduces stability and channel activity. These results contrast with previous patch clamp data that showed low-pH activation, which we have not been able to reproduce.
The Genomes, Proteomes, and Structures of Three Novel Phages That Infect the Bacillus cereus Group and Carry Putative Virulence Factors
Authors: Grose Julianne H. , Belnap David M. , Jensen Jordan D. , Mathis Andrew D. , Prince John T. , Merrill Bryan D. , Burnett Sandra H. , Breakwell Donald P. 
Published: August 2014

ABSTRACT

This article reports the results of studying three novel bacteriophages, JL, Shanette, and Basilisk, which infect the pathogen
Bacillus cereus
and carry genes that may contribute to its pathogenesis. We analyzed host range and superinfection ability, mapped their genomes, and characterized phage structure by mass spectrometry and transmission electron microscopy (TEM). The JL and Shanette genomes were 96% similar and contained 217 open reading frames (ORFs) and 220 ORFs, respectively, while Basilisk has an unrelated genome containing 138 ORFs. Mass spectrometry revealed 23 phage particle proteins for JL and 15 for Basilisk, while only 11 and 4, respectively, were predicted to be present by sequence analysis. Structural protein homology to well-characterized phages suggested that JL and Shanette were members of the family
Myoviridae
, which was confirmed by TEM. The third phage, Basilisk, was similar only to uncharacterized phages and is an unrelated siphovirus. Cryogenic electron microscopy of this novel phage revealed a T=9 icosahedral capsid structure with the major capsid protein (MCP) likely having the same fold as bacteriophage HK97 MCP despite the lack of sequence similarity. Several putative virulence factors were encoded by these phage genomes, including TerC and TerD involved in tellurium resistance. Host range analysis of all three phages supports genetic transfer of such factors within the
B. cereus
group, including
B. cereus
,
B. anthracis
, and
B. thuringiensis
. This study provides a basis for understanding these three phages and other related phages as well as their contributions to the pathogenicity of
B. cereus
group bacteria.

IMPORTANCE
The
Bacillus cereus
group of bacteria contains several human and plant pathogens, including
B. cereus
,
B. anthracis
, and
B. thuringiensis
. Phages are intimately linked to the evolution of their bacterial hosts and often provide virulence factors, making the study of
B. cereus
phages important to understanding the evolution of pathogenic strains. Herein we provide the results of detailed study of three novel
B. cereus
phages, two highly related myoviruses (JL and Shanette) and an unrelated siphovirus (Basilisk). The detailed characterization of host range and superinfection, together with results of genomic, proteomic, and structural analyses, reveal several putative virulence factors as well as the ability of these phages to infect different pathogenic species.
trans
-Protease Activity and Structural Insights into the Active Form of the Alphavirus Capsid Protease
Authors: Aggarwal Megha , Dhindwal Sonali , Kumar Pravindra , Kuhn Richard J. , Tomar Shailly 
Published: August 2014

ABSTRACT

The alphavirus capsid protein (CP) is a serine protease that possesses
cis
-proteolytic activity essential for its release from the nascent structural polyprotein. The released CP further participates in viral genome encapsidation and nucleocapsid core formation, followed by its attachment to glycoproteins and virus budding. Thus, protease activity of the alphavirus capsid is a potential antialphaviral target to arrest capsid release, maturation, and structural polyprotein processing. However, the discovery of capsid protease inhibitors has been hampered due to the lack of a suitable screening assay and of the crystal structure in its active form. Here, we report the development of a
trans
-proteolytic activity assay for Aura virus capsid protease (AVCP) based on fluorescence resonance energy transfer (FRET) for screening protease inhibitors. Kinetic parameters using fluorogenic peptide substrates were estimated, and the

K
m

value was found to be 2.63 ± 0.62 μM while the
k
cat
/

K
m

value was 4.97 × 10
4
M
−1
min
−1
. Also, the crystal structure of the
trans
-active form of AVCP has been determined to 1.81-Å resolution. Structural comparisons of the active form with the crystal structures of available substrate-bound mutant and inactive blocked forms of the capsid protease identify conformational changes in the active site, the oxyanion hole, and the substrate specificity pocket residues, which could be critical for rational drug design.

IMPORTANCE
The alphavirus capsid protease is an attractive antiviral therapeutic target. In this study, we have described the formerly unappreciated
trans
-proteolytic activity of the enzyme and for the first time have developed a FRET-based protease assay for screening capsid protease inhibitors. Our structural studies unveil the structural features of the
trans
-active protease, which has been previously proposed to exist in the natively unfolded form (M. Morillas, H. Eberl, F. H. Allain, R. Glockshuber, and E. Kuennemann, J. Mol. Biol. 376:721–735, 2008, doi:http://dx.doi.org/10.1016/j.jmb.2007.11.055). The different enzymatic forms have been structurally compared to reveal conformational variations in the active and substrate binding sites. The flexible active-site residue Ser218, the disordered C-terminal residues after His261, and the presence of a water molecule in the oxyanion hole of AVCPΔ2 (AVCP with a deletion of the last two residues at the C terminus) reveal the effect of the C-terminal Trp267 deletion on enzyme structure. New structural data reported in this study along with the fluorogenic assay will be useful in substrate specificity characterization, high-throughput protease inhibitor screening, and structure-based development of antiviral drugs.
Effects of Ear Acupuncture Therapy for Obesity on the Depression of Obese Women
Authors: Set Turan , Cayir Yasemin , Pirim Asuman Bihter Guven 
Published: August 2014

Background Obesity is one of the leading health risks worldwide, and depression is among the leading causes of the burden of disease. These disorders are increasingly prevalent as comorbidities. Depressive symptoms are associated with obesity, and are more common in women. Objective To evaluate the effectiveness of ear acupuncture for obesity on the depression of obese women. Methods After baseline testing, 30 eligible patients with body mass index (BMI) >29.9 kg/m2 were included. The Beck Depression Inventory for Primary Care (BDI-PC) was used to assess changes in depression. BMI was also measured. Patients had six ear acupuncture sessions, every 15 days and were followed up for 3 months. Twenty four patients completed the study. Results The mean±SD age of patients was 42.9±9.0 years. Their mean±SD BMI was 39.0±4.7 kg/m2 before acupuncture, decreasing to 37.2±4.3 kg/m2 after acupuncture therapy (p<0.001). The mean depression score was 4.4±2.3 before acupuncture, decreasing to 2.7±1.4 (p<0.001) after treatment. There was no significant correlation between BMI and depression score before acupuncture therapy (p=0.104). After acupuncture therapy, no significant correlation was found between the percentage reduction of BMI and percentage reduction of the depression score (p=0.119). Conclusions Further research into the effects of ear acupuncture in the management of obesity and depression is justified.
The role of stress on chemical compaction of illite shale powder
Authors: Bruijn Rolf H. C. , Almqvist Bjarne S. G. 
Published: August 2014

Abstract
Experimental compaction curves for mud are key factors in sedimentary basin models but they are poor at predicting porosity evolution beyond 2.5 km depth, where chemical compaction dominates shale diagenesis. This study presents the results of experimental simulation of diagenesis and low-grade metamorphism of an illite shale powder. By applying amphibolite facies conditions using high-pressure–high-temperature deformation apparatus, the transformation of illite to phengite that takes place under anchizone and epizone metamorphic conditions could be accelerated and completed within laboratory timescales. In accordance with observation of naturally compacted shales, our experimentally compacted metapelites range in porosity from 1% to 16% and contain authigenic phengite, biotite, and quartz. By compacting illite shale powder under both lithostatic and non-lithostatic conditions, the role of stress or tectonic forces during diagenesis could be evaluated. Based on microstructural and chemical similarities we infer that both types of samples compact in the same way, indicating that chemical compaction is unaffected by differential stress. Basin evolution models can therefore extend the 1D generalization of the stress field to depths where chemical compaction takes place. However, as chemical compaction enhances mineral alignment, anisotropy of physical properties such as permeability and sonic velocities can change substantially.
Outcome in Women with Traumatic Brain Injury Admitted to a Level 1 Trauma Center
Authors: de Guise Elaine , LeBlanc Joanne , Dagher Jehane , Tinawi Simon , Lamoureux Julie , Marcoux Judith , Maleki Mohammed , Feyz Mitra 
Published: August 2014

Background. The aim of this study was to compare acute outcome between men and women after sustaining a traumatic brain injury (TBI). Methods. A total of 5,642 patients admitted to the Traumatic Brain Injury Program of the McGill University Health Centre-Montreal General Hospital between 2000 and 2011 and diagnosed with a TBI were included in the study. The overall percentage of women with TBI was 30.6% (n= 1728). Outcome measures included the length of stay (LOS), the Extended Glasgow Outcome Scale (GOSE), the functional independence measure instrument (FIM), discharge destination, and mortality rate. Results. LOS, GOSE, the FIM ratings, and discharge destination did not show significant differences between genders once controlling for several confounding variables and running the appropriate diagnostic tests (P<0.05). However, women had less chance of dying during their acute care hospitalization than men of the same age, with the same TBI severity and following the same mechanism of injury. Although gender was a statistically significant predictor, its contribution in explaining variation in mortality was small. Conclusion. More research is needed to better understand gender differences in mortality; as to date, the research findings remain inconclusive.
Development of siRNA Payloads to Target KRAS-Mutant Cancer
Authors: Yuan Tina L. , Fellmann Christof , Lee Chih-Shia , Ritchie Cayde D. , Thapar Vishal , Lee Liam C. , Hsu Dennis J. , Grace Danielle , Carver Joseph O. , Zuber Johannes , Luo Ji , McCormick Frank , Lowe Scott W. 
Published: August 2014

Abstract
RNAi is a powerful tool for target identification and can lead to novel therapies for pharmacologically intractable targets such as KRAS. RNAi therapy must combine potent siRNA payloads with reliable in vivo delivery for efficient target inhibition. We used a functional “Sensor” assay to establish a library of potent siRNAs against RAS pathway genes and to show that they efficiently suppress their targets at low dose. This reduces off-target effects and enables combination gene knockdown. We administered Sensor siRNAs in vitro and in vivo and validated the delivery of KRAS siRNA alone and siRNA targeting the complete RAF effector node (A/B/CRAF) as promising strategies to treat KRAS-mutant colorectal cancer. We further demonstrate that improved therapeutic efficacy is achieved by formulating siRNA payloads that combine both single-gene siRNA and node-targeted siRNAs (KRAS + PIK3CA/B). The customizable nature of Sensor siRNA payloads offers a universal platform for the combination target identification and development of RNAi therapeutics.
Significance: To advance RNAi therapy for KRAS-mutant cancer, we developed a validated siRNA library against RAS pathway genes that enables combination gene silencing. Using an in vivo model for real-time siRNA delivery tracking, we show that siRNA-mediated inhibition of KRAS as well as RAF or PI3K combinations can impair KRAS-mutant colorectal cancer in xenograft models. Cancer Discov; 4(10); 1182–97. ©2014 AACR.
This article is highlighted in the In This Issue feature, p. 1103
Transforming HRD
Authors: Bierema Laura , Callahan Jamie L. 
Published: August 2014

The Problem Human resource development (HRD) has become powerfully influenced by a dominant rationality in which masculine characteristics of assertiveness, objectivity, control, and performance are privileged without question, resulting in inequitable practices and social systems such as sexism, racism, and capitalism. The humanistic roots of the field of HRD have been co-opted into serving organizations at the expense of workers and other stakeholders. The current frameworks used to understand and apply practices within the field are not sufficient to reclaim the HRD voice of organizational conscience. The Solution This article defines critical human resource development (CHRD) and offers a framework for envisioning the field that restructures the “holy trinity” of HRD known as Training & Development, Career Development, and Organization Development. We make a case for why a CHRD is needed and provide an overview of key, and contested, issues of practice for HRD (and CHRD) professionals—relating, learning, changing, and organizing. The Stakeholders Scholars and practitioners invested in exploring a new framework of CHRD.