bluuebunny/crossref_metadata_2025 huggingface dataset:
Mini-open double row gluteus medius repair provides good short-term functional outcomes
Authors: DeFroda Steven , Silverman Ariel , Quinn Matthew , Tabaddor Ramin
Published: October 2019

Gluteus medius (GM) tears are recognized as a significant cause of lateral hip pain. While non-operative management can be effective, those who fail this treatment modality may be indicated for operative intervention. There is no widely agreed upon ‘gold standard’ technique with regards to open, mini-open and endoscopic repair. Our study prospectively enrolled 31 patients undergoing the authors preferred ‘mini-open’ repair technique with patients completing pre- and post-operative patient reported outcome measures (PROMs) in the form of the Modified Harris Hip Score, Visual Analogue pain Scale, Hip Outcomes Score for Activities of Daily Living and Hip Outcomes Score for Sports-Related Activities (HOS-SSS). The effect of anxiety/depression on outcomes was also examined. Patients had an average follow-up of 6 months. There was a statistically significant increase in all PROMs in the 31 patients undergoing mini-open repair. A sub-group of patients with self-reported history of anxiety/depression via patient intake paperwork experienced less improvement than those without, however this cohort still had significant improvement in all categories except HOS-SSS. Our study shows that a mini-open GM repair technique provides good patient reported outcomes at 6 months, and allows for improved cosmesis compared with traditional open techniques utilizing a larger surgical incision. It is important to counsel patients with a history of anxiety/depression that while they can expect significant functional improvement, that their improvement may be less than patients without these comorbidities.
Propagation, cocoon formation, and resultant destabilization of relativistic jets
Authors: Matsumoto Jin , Masada Youhei
Published: October 2019

A cocoon is a by-product of a propagating jet that results from shock heating at the jet head. Herein, considering simultaneous cocoon formation, we study the stability of relativistic jets propagating through the uniform ambient medium. Using a simple analytic argument, we demonstrate that independent from the jet launching condition, the effective inertia of the jet is larger than that of the cocoon when the fully relativistic jet oscillates radially owing to the pressure mismatch between jet and cocoon. In such situations, it is expected that the onset condition for the oscillation-induced Rayleigh–Taylor instability is satisfied at the jet interface, resulting in the destabilization of the relativistic jet during its propagation. We have quantitatively verified and confirmed our prior expectation by performing relativistic hydrodynamic simulations in three dimensions. The possible occurrences of the Richtmyer–Meshkov instability, oscillation-induced centrifugal instability, and Kelvin–Helmholtz instability are also discussed.
Choked accretion: from radial infall to bipolar outflows by breaking spherical symmetry
Authors: Aguayo-Ortiz Alejandro , Tejeda Emilio , Hernandez X
Published: October 2019

Steady-state, spherically symmetric accretion flows are well understood in terms of the Bondi solution. Spherical symmetry, however, is necessarily an idealized approximation to reality. Here we explore the consequences of deviations away from spherical symmetry, first through a simple analytic model to motivate the physical processes involved, and then through hydrodynamical, numerical simulations of an ideal fluid accreting on to a Newtonian gravitating object. Specifically, we consider axisymmetric, large-scale, small-amplitude deviations in the density field such that the equatorial plane is overdense as compared to the polar regions. We find that the resulting polar density gradient dramatically alters the Bondi result and gives rise to steady-state solutions presenting bipolar outflows. As the density contrast increases, more and more material is ejected from the system, attaining speeds larger than the local escape velocities for even modest density contrasts. Interestingly, interior to the outflow region, the flow tends locally towards the Bondi solution, with a resulting total mass accretion rate through the inner boundary choking at a value very close to the corresponding Bondi one. Thus, the numerical experiments performed suggest the appearance of a maximum achievable accretion rate, with any extra material being ejected, even for very small departures from spherical symmetry.
The LOFAR Tied-Array All-Sky Survey (LOTAAS): Characterization of 20 pulsar discoveries and their single-pulse behavior
Authors: Michilli D , Bassa C , Cooper S , Hessels J W T , Kondratiev V I , Sanidas S , Stappers B W , Tan C M , van Leeuwen J , Cognard I , Grießmeier J-M , Lyne A G , Verbiest J P W , Weltevrede P
Published: October 2019

We are using the LOw-Frequency ARray (LOFAR) to perform the LOFAR Tied-Array All-Sky (LOTAAS) survey for pulsars and fast transients. Here we present the astrometric and rotational parameters of 20 pulsars discovered as part of LOTAAS. These pulsars have regularly been observed with LOFAR at 149 MHz and the Lovell telescope at 1532 MHz, supplemented by some observations with the Lovell telescope at 334 MHz and the Nançay Radio Telescope at 1484 MHz. Timing models are calculated for the 20 pulsars, some of which are among the slowest-spinning pulsars known. PSR J1236−0159 rotates with a period P ∼ 3.6 s, while 5 additional pulsars show P > 2 s. Also, the spin-down rates $\dot{P}$ are, on average, low, with PSR J0815+4611 showing $\dot{P} \sim 4\times 10^{-18}$. Some of the pulse profiles, generically single-peaked, present complex shapes evolving with frequency. Multi-frequency flux measurements show that these pulsars have generically relatively steep spectra but exceptions are present, with values ranging between ∼−4 and −1. Among the pulsar sample, a large fraction shows large single-pulse variability, with 4 pulsars being undetectable more than $15\%$ of the time and one tentatively classified as a Rotating Radio Transient. Two single-peaked pulsars show drifting sub-pulses.
The latest update on individual external doses in an early stage after the Fukushima nuclear accident
Authors: Ishikawa Tetsuo , Yasumura Seiji , Akahane Keiichi , Yonai Shunsuke , Ohtsuru Akira , Sakai Akira , Sakata Ritsu , Ohira Tetsuya , Kamiya Kenji
Published: October 2019

Following the Fukushima Daiichi Nuclear Power Plant accident, a survey for estimating individual external doses for the first 4 months after the accident was started, and it remains ongoing. Since the authors’ previous paper, 44 605 new dose estimates have been made. The new dose estimates increase the number of dose estimates to 465 999 and are reported in this note. Since the previous paper, most of the recently collected responses have been gotten through public relations activities to encourage responses across the prefecture. Thus, recent respondents might be biased (‘selection bias’). Also, the dose estimates were based on self-administered responses about personal behaviour, which relied on memories of residents. In this respect, incorrect behaviour records possibly resulted as memories have faded over time (‘recall bias’). However, the effects of these biases on dose distribution on a whole-prefecture basis seemed to be small.
The role of sleep hygiene in the risk of Shift Work Disorder in nurses
Authors: Booker Lauren A , Barnes Maree , Alvaro Pasquale , Collins Allison , Chai-Coetzer Ching Li , McMahon Marcus , Lockley Steven W , Rajaratnam Shantha M W , Howard Mark E , Sletten Tracey L
Published: October 2019

A high proportion (20%–30%) of shift workers experience Shift Work Disorder (SWD), characterized by chronic sleepiness and/or insomnia associated with work schedules. The reasons for individual variation in shift work tolerance are not well understood, however. The aim of this study was to identify individual factors that contribute to the risk of SWD. Nurses (n = 202) were categorized as low or high risk of SWD based on the Shift Work Disorder Questionnaire. Participants provided demographic and lifestyle information and completed the Sleep Hygiene Index (SHI) and Morningness–Eveningness Questionnaire (MEQ). High risk of SWD was associated with poorer sleep hygiene (SHI, 35.41 ± 6.19 vs. 31.49 ± 7.08, p < .0001) and greater eveningness (MEQ, 34.73 ± 6.13 vs. 37.49 ± 6.45, p = .005) compared to low risk. No other factors, including body mass index, marital status, having children, or caffeine or alcohol intake were significant. Logistic regression showed that SHI was the most significant contributing factor to SWD risk (odds ratio [OR] = 1.09, 95% confidence interval [CI] = 1.04 to 1.14). Standardized odds ratio further revealed that with every unit increase on the SHI score, the odds of being at high risk of SWD increased by 80% (OR = 1.84). Most individuals at high risk of SWD reported “always” or “frequently” going to bed at different times (79%) and waking at different times (83%; compared to 58%, p = .017, and 61%, p = .002, respectively for the low-risk group), as well as going to bed stressed/angry (67% vs. 41%, p < .0001) and/or planning/worrying in bed (54% vs. 22%, p < .0001). Interventions aimed at improving sleep hygiene practices and psychological health of shift workers may help reduce the risk of SWD.
Framing multiple sclerosis under a polysomnographic perspective
Authors: Tanioka Kosuke , Castelnovo Anna , Tachibana Naoko , Miano Silvia , Zecca Chiara , Gobbi Claudio , Manconi Mauro
Published: October 2019

Multiple sclerosis (MS) is a mainly demyelinating, autoimmune, and disabling neurological disease. In addition to well-known clinically evident symptoms such as coordination or motor problems, increasing attention has been posed to a constellation of less evident symptoms significantly contributing to the clinical impact of MS. Among others, sleep symptoms have been only recently explored. This systematic review summarizes objective sleep findings detected by using polysomnography and their relationship with clinical variables in MS patients. While it is well known that sleep disorders are frequent in MS, objective clinical data are still scarce. Literature based on subjective reports indicate sleep disorders as highly frequent in MS patients; however, objective data are still scarce. New large case-control instrumental investigations are warranted to establish the real objective entity and impact of sleep comorbidities.
To reserve or not to reserve? That is the question—Part I
Authors: Goodman Dawn , Hirsch Phineas
Published: October 2019

In this article, we will address why it has become so popular to reserve or grant powers and how and where to do so. In Part II, we will ask what can possibly go wrong with the settlor/grantor and his appointees in charge.
Engineering Plant Resistance to Tomato Yellow Leaf Curl Thailand Virus Using a Phloem-Specific Promoter Expressing Hairpin RNA
Authors: Tzean Yuh , Chang Ho-Hsiung , Tu Tsui-Chin , Hou Bo-Han , Chen Ho-Ming , Chiu Yi-Shu , Chou Wei-Yi , Chang Li , Yeh Hsin-Hung
Published: October 2019

Transgenic approaches employing RNA interference (RNAi) strategies have been successfully applied to generate desired traits in plants; however, variations between RNAi transgenic siblings and the ability to quickly apply RNAi resistance to diverse cultivars remain challenging. In this study, we assessed the promoter activity of a cauliflower mosaic virus 35S promoter (35S) and a phloem-specific promoter derived from rice tungro bacilliform virus (RTBV) and their efficacy to drive RNAi against the endogenous glutamate-1-semialdehyde aminotransferase gene (GSA) that acts as a RNAi marker, through chlorophyll synthesis inhibition, and against tomato yellow leaf curl Thailand virus (TYLCTHV), a begomovirus (family Geminiviridae) reported to be the prevalent cause of tomato yellow leaf curl disease (TYLCD) in Taiwan. Transgenic Nicotiana benthamiana expressing hairpin RNA of GSA driven by either the 35S or RTBV promoter revealed that RTBV::hpGSA induced stronger silencing along the vein and more uniformed silencing phenotype among its siblings than 35S::hpGSA. Analysis of transgenic N. benthamiana, 35S::hpTYLCTHV, and RTBV::hpTYLCTHV revealed that, although 35S::hpTYLCTHV generated a higher abundance of small RNA than RTBV::hpTYLCTHV, RTBV::hpTYLCTHV transgenic plants conferred better TYLCTHV resistance than 35S::hpTYLCTHV. Grafting of wild-type (WT) scions to TYLCTHV RNAi rootstocks allowed transferable TYLCTHV resistance to the scion. A TYLCTHV-inoculation assay showed that noninfected WT scions were only observed when grafted to RTBV::hpTYLCTHV rootstocks but not 35S::hpTYLCTHV nor WT rootstocks. Together, our findings demonstrate an approach that may be widely applied to efficiently confer TYLCD resistance.
Cataract in the human lens: a systematic review of proteomic studies
Authors: Karakosta Christina , Tzamalis Argyrios , Aivaliotis Michalis , Tsinopoulos Ioannis
Published: October 2019

Background/Aim

The aim of this systematic review is to identify all the available data on human lens proteomics with a critical role to age-related cataract formation in order to elucidate the physiopathology of the aging lens.

Methods

We searched on Medline and Cochrane databases. The search generated 328 manuscripts. We included nine original proteomic studies that investigated human cataractous lenses.

Results

Deamidation was the major age-related post-translational modification. There was a significant increase in the amount of αA-crystallin D-isoAsp58 present at all ages, while an increase in the extent of Trp oxidation was apparent in cataract lenses when compared to aged normal lenses. During aging, enzymes with oxidized cysteine at critical sites included GAPDH, glutathione synthase, aldehyde dehydrogenase, sorbitol dehydrogenase, and PARK7.

Conclusion

D-isoAsp in αA crystallin could be associated with the development of age-related cataract in human, by contributing to the denaturation of a crystallin, and decreasing its ability to act as a chaperone. Oxidation of Trp may be associated with nuclear cataract formation in man, while the role of oxidant stress in age-related cataract formation is dominant.

Synopsis

The oxidative stress and the post-translational modification of deamidation in lens crystallins seem to play a significant role in the formation of age-related cataract in human.
Profiles of cognitive change in preclinical Alzheimer’s disease using change-point analysis
Authors: Williams Owen A , An Yang , Armstrong Nicole M , Kitner-Triolo Melissa , Ferrucci Luigi , Resnick Susan M
Published: October 2019

Introduction

Change-point analyses are increasingly used to identify the temporal stages of accelerated cognitive decline in the preclinical stages of Alzheimer’s Disease (AD). However, statistical comparisons of change-points between specific cognitive measures have not been reported.

Methods

165 older adults (baseline age range: 61.1-91.2) from the Baltimore Longitudinal Study of Aging developed AD during follow-up. Linear and non-linear mixed models were fit for 11 cognitive measures to determine change-points in rates of decline before AD diagnosis. Bootstrapping was used to compare the timing of change-points across cognitive measures.

Results

Change-points followed by accelerated decline ranged from 15.5 years (Card Rotations) to 1.9 years (Trail-Making A) before AD diagnosis. Accelerated decline in Card Rotations occurred significantly earlier than all other measures, including learning and memory measures.

Discussion

Results suggest that visuospatial ability, as assessed by Card Rotations, may have the greatest utility as an early predictive tool in identifying preclinical AD.
Effective Tyrosine Kinase Inhibitors result in the intracellular accumulation of EGFR and allows response prediction in patients
Authors: de Wit Maurice , Gao Ya , Mercieca Darlene , de Heer Iris , Valkenburg Bart , van Royen Martin , Aerts Joachim , Smitt Peter Sillevis , French Pim
Published: October 2019

Clinical responses to EGFR tyrosine kinase inhibitors are restricted only to tumors harboring specific activating mutations and even then, not all tyrosine kinase inhibitors provide clinical benefit. We here show that the addition of EGFR-TKIs results in a strong and rapid intracellular accumulation of the protein. However, this accumulation was observed only in the context of a combination of a TKI-sensitive mutation with a clinically effective TKI: TKI-insensitive mutations did not show this accumulation nor did clinically ineffective TKIs induce accumulation. All TKIs effectively inhibited EGFR phosphorylation and downstream pathway activation, irrespective of the mutation present in EGFR. The discrepancy between molecular activity of TKIs and their efficacy in patients therefore is mimicked by the mutation- and TKI-specificity of intracellular accumulation. Using this intracellular accumulation as assay, we were able to predict response to gefitinib in a panel of cell-lines (harboring different EGFR mutations) and predicted clinical benefit to EGFR TKIs on a cohort of unselected pulmonary adenocarcinoma patients (hazard ratio 0.21, P=0.0004). Even in patients harboring rare mutations with unknown TKI-sensitivity, intracellular accumulation was predictive of the clinical response. The intracellular accumulation depended on a continued presence of TKI indicating that TKIs exert a continued effect on the protein even after its dephosphorylation. It is therefore possible that accumulation is caused by conformational changes induced by both the mutation and the TKI and this change induces a block in intracellular trafficking. Interestingly, intracellular accumulation was observed independent of the genetic background of the cell, indicating that accumulation is almost entirely dictated by the combination of mutation and TKI. Our results therefore suggest that TKI-sensitivity is tumor-type independent.
qDRIP: Quantitative differential RNA:DNA hybrid immunoprecipitation sequencing
Authors: Crossley Madzia P , Bocek Michael J , Hamperl Stephan , Swigut Tomek , Cimprich Karlene A.
Published: October 2019

R-loops are dynamic, co-transcriptional nucleic acid structures that facilitate physiological processes and cause DNA damage in certain contexts. Perturbations of transcription or R-loop resolution are expected to change their genomic distribution. Next-generation sequencing approaches to map RNA:DNA hybrids, a component of R-loops, have so far not allowed quantitative comparisons between such conditions. Here we describe quantitative differential RNA:DNA immunoprecipitation (qDRIP), a method combining synthetic RNA:DNA-hybrid internal standards with high-resolution, strand-specific sequencing. We show that qDRIP avoids biases inherent to read-count normalization by accurately profiling signal in regions unaffected by transcription inhibition in human cells, and by facilitating accurate differential peak calling between conditions. Finally, we use these quantitative comparisons to make the first estimates of the absolute count of RNA:DNA hybrids per cell and their half-lives genome-wide. Overall, qDRIP allows for accurate normalization in conditions where R-loops are perturbed and for quantitative measurements that provide previously unattainable biological insights.
Systematic identification of A-to-I editing associated regulators from multiple human cancers
Authors: Gu Tongjun , Fu Audrey Qiuyan , Bolt Michael J. , Zhao Xiwu
Published: October 2019

A-to-I editing is the most common editing type in human that is catalyzed by ADAR family members (ADARs), ADAR1 and ADAR2. Millions of A-to-I editing sites have been discovered recently, however, the regulation mechanisms of the RNA editing process are still not clear. Here we developed a two-step logistic regression model to identify genes that are potentially involved in RNA editing process in four human cancers. The first step by classifying the editing sites into different categories assists the analysis at the second step. In the first step, ADAR1 was identified as the enzyme that associated with the majority of the A-to-I editing sites. Thus, ADAR1 was taken as a control gene in the second step to identify genes that have a stronger effect on editing sites than ADAR1. In addition, the detectable interferons and their receptors were used as covariates in the both steps to account for potential association caused by interferons. Using our advanced method, we successfully found a set of genes that were significantly positively or negatively associated (PA or NA) with specific sets of RNA editing sites. We highlighted two genes, SRSF5 and MIR22HG which were supported by multiple evidences. Most PA and NA genes were unique to each cancer, and only a few shared across two cancers. Pathway enrichment analysis showed that the PA genes from the four cancer types were enriched in Immune System, while the NA genes were enriched in two pathways: Metabolism of RNA, and Metabolism. The functional similarity of the PA and NA genes across all the four cancers indicates that even though most of the editing associated genes were unique to each cancer, they may impact on editing process through common pathways. Interestingly, the PA genes from kidney cancer were enriched for survival-associated genes while the NA genes were depleted of these genes, indicating that the PA genes may play more important roles in kidney cancer development.
RNAfamProb Plus NeoFold: Estimations of Posterior Probabilities on RNA Structural Alignment and RNA Secondary Structures with Incorporating Homologous-RNA Sequences
Authors: Tagashira Masaki , Asai Kiyoshi
Published: October 2019

Motivation

The simultaneous optimization of the sequence alignment and secondary structures among RNAs, structural alignment, has been required for the more appropriate comparison of functional ncRNAs than sequence alignment. Pseudo-probabilities given RNA sequences on structural alignment have been desired for more-accurate secondary structures, sequence alignments, consensus secondary structures, and structural alignments. However, any algorithms have not been proposed for these pseudo-probabilities.

Results

We invented the RNAfamProb algorithm, an algorithm for estimating these pseudo-probabilities. We performed the application of these pseudo-probabilities to two biological problems, the visualization with these pseudo-probabilities and maximum-expected-accuracy secondary-structure (estimation). The RNAfamProb program, an implementation of this algorithm, plus the NeoFold program, a maximum-expected-accuracy secondary-structure program with these pseudo-probabilities, demonstrated prediction accuracy better than three state-of-the-art programs of maximum-expected-accuracy secondary-structure while demanding running time far longer than these three programs as expected due to the intrinsic serious problem-complexity of structural alignment compared with independent secondary structure and sequence alignment. Both the RNAfamProb and NeoFold programs estimate matters more accurately with incorporating homologous-RNA sequences.

Availability

The source code of each of these two programs is available on each of “https://github.com/heartsh/rnafamprob” and “https://github.com/heartsh/neofold”.

Contact

“tagashira_masaki_17@stu-cbms.k.u-tokyo.ac.jp” and “asai@k.u-tokyo.ac.jp”.

Supplementary information

Supplementary data are available at Bioinformatics online.
InterPep2: Global Peptide-Protein Docking with Structural Templates
Authors: Johansson-Åkhe Isak , Mirabello Claudio , Wallner Björn
Published: October 2019

Motivation

Interactions between proteins and peptides or peptide-like intrinsically disordered regions are involved in many important biological processes, such as gene expression and cell life-cycle regulation. Experimentally determining the structure of such interactions is time-consuming, and because of the disordered nature of the ligand, the interactions are especially difficult to predict through software, requiring specialized solutions. Although several prediction-methods exist, most are limited in performance or availability.

Results

InterPep2 is a freely available method for predicting the structure of peptide-protein interactions. We have previously shown that structural templates can be used to accurately predict peptide-protein binding sites, and that using templates from regular protein-protein interactions will increase the number of sites found. Here, we show that the same principle can be extended to dock the peptide to the binding surface using InterPep2. A key component of InterPep2 is the ability to score plausible interaction templates using a RandomForest trained to predict the DockQ-score using sequence and structural features. InterPep2 is tested on a difficult dataset of 251 peptide-protein complexes, where it correctly positions 136 (54%) at the correct site compared to 114 (45%) for the second best method. Analyzing the confidence score InterPep2 recalls more true positives across all specificity levels compared to the second best method, for example at 10% False Positive Rate it correctly identifies 59% of the complexes compared to 44% for the second best method.

Availability

The program is available from:http://wallnerlab.org/InterPep

Contact

Björn Wallnerbjorn.wallner@liu.se
Dysregulation of temporal dynamics of synchronous neural activity in adolescents on autism spectrum
Authors: Malaia Evie A. , Ahn Sungwoo , Rubchinsky Leonid L
Published: October 2019

Autism spectrum disorder is increasingly understood to be based on atypical signal transfer among multiple interconnected networks in the brain. Relative temporal patterns of neural activity have been shown to underlie both the altered neurophysiology and the altered behaviors in a variety of neurogenic disorders. We assessed brain network dynamics variability in Autism Spectrum Disorders (ASD) using measures of synchronization (phase-locking) strength, and timing of synchronization and desynchronization of neural activity (desynchronization ratio) across frequency bands of resting state EEG. Our analysis indicated that fronto-parietal synchronization is higher in ASD, but with more short periods of desynchronization. It also indicates that the relationship between the properties of neural synchronization and behavior is different in ASD and typically developing populations. Recent theoretical studies suggest that neural networks with high desynchronization ratio have increased sensitivity to inputs. Our results point to the potential significance of this phenomenon to autistic brain. This sensitivity may disrupt production of an appropriate neural and behavioral responses to external stimuli. Cognitive processes dependent on integration of activity from multiple networks may be, as a result, particularly vulnerable to disruption.

Lay Summary

Parts of the brain can work together by synchronizing activity of the neurons. We recorded electrical activity of the brain in adolescents with autism spectrum disorder, and then compared the recording to that of their peers without the diagnosis. We found that in participants with autism, there were a lot of very short time periods of non-synchronized activity between frontal and parietal parts of the brain. Mathematical models show that the brain system with this kind of activity is very sensitive to external events.
Amino and PEG-Amino Graphene Oxide Grids Enrich and Protect Samples for High-resolution Single Particle Cryo-electron Microscopy
Authors: Wang Feng , Yu Zanlin , Betegon Miguel , Campbell Melody , Aksel Tural , Zhao Jianhua , Li Sam , Douglas Shawn M. , Cheng Yifan , Agard David A.
Published: October 2019

Cryo-EM samples prepared using the traditional methods often suffer from too few particles, poor particle distribution, or strongly biased orientation, or damage from the air-water interface. Here we report that functionalization of graphene oxide (GO) coated grids with amino groups concentrates samples on the grid with improved distribution and orientation. By introducing a PEG spacer, particles are kept away from both the GO surface and the air-water interface, protecting them from potential denaturation.
Cryptococcus neoformansChitin Synthase 3 (Chs3) Plays a Critical Role in Dampening Host Inflammatory Responses
Authors: Hole Camaron R. , Lam Woei C. , Upadhya Rajendra , Lodge Jennifer K.
Published: October 2019

Cryptococcus neoformansinfections are significant causes of morbidity and mortality among AIDS patients and the third most common invasive fungal infection in organ transplant recipients. One of the main interfaces between the fungus and the host is the fungal cell wall. The cryptococcal cell wall is unusual among human pathogenic fungi in that the chitin is predominantly deacetylated to chitosan. Chitosan deficient strains ofC. neoformanswere found to be avirulent and rapidly cleared from the murine lung. Moreover, infection with a chitosan deficientC. neoformanslacking three chitin deacetylases (cda1Δ2Δ3Δ) was found to confer protective immunity to a subsequent challenge with a virulent wild type counterpart. In addition to the chitin deacetylases, it was previously shown that chitin synthase 3 (Chs3) is also essential for chitin deacetylase mediated formation of chitosan. Mice inoculated withchs3Δat a dose previously shown to induce protection with cda1Δ2Δ3Δdie within 36 hours after installation of the organism. Mortality was not dependent on viable fungi as mice inoculated with heat-killed preparation ofchs3Δdied at the same rate as mice inoculated with livechs3Δ, suggesting the rapid onset of death was host mediated likely caused by an over exuberant immune response. Histology, cytokine profiling, and flow cytometry indicates a massive neutrophil influx in the mice inoculated withchs3Δ. Mice depleted of neutrophils survivedchs3Δinoculation indicating that death was neutrophil mediated. Altogether, these studies lead us to conclude that Chs3, along with chitosan, plays critical roles in dampening cryptococcal induced host inflammatory responses.

IMPORTANCE

Cryptococcus neoformansis the most common disseminated fungal pathogen in AIDS patients, resulting in ∼200,000 deaths each year. There is a pressing need for new treatments for this infection, as current antifungal therapy is hampered by toxicity and/or the inability of the host’s immune system to aid in resolution of the disease. An ideal target for new therapies is the fungal cell wall. The cryptococcal cell wall is different than many other pathogenic fungi in that it contains chitosan. Strains that have decreased chitosan are less pathogenic and strains that are deficient in chitosan are avirulent and can induce protective responses. In this study we investigated the host responses tochs3Δ, a chitosan-deficient strain, and found mice inoculated withchs3Δ all died within 36 hours and death was associated with an aberrant hyperinflammatory immune response driven by neutrophils, indicating that chitosan is critical in modulating the immune response toCryptococcus.
The Dynamics of Influenza A H3N2 Defective Viral Genomes from a Human Challenge Study
Authors: Martin Michael A. , Kaul Drishti , Tan Gene S. , Woods Christopher W. , Koelle Katia
Published: October 2019

The rapid evolution of influenza is an important contributing factor to its high worldwide incidence. The emergence and spread of genetic point mutations has been thoroughly studied both within populations and within individual hosts. In addition, influenza viruses are also known to generate genomic variation during their replication in the form of defective viral genomes (DVGs). These DVGs are formed by internal deletions in at least one gene segment that render them incapable of replication without the presence of wild-type virus. DVGs have previously been identified in natural human infections and may be associated with less severe clinical outcomes. These studies have not been able to address how DVG populations evolvein vivoin individual infections due to their cross-sectional design. Here we present an analysis of DVGs present in samples from two longitudinal influenza A H3N2 human challenge studies. We observe the generation of DVGs in almost all subjects. Although the genetic composition of DVG populations was highly variable, identical DVGs were observed both between multiple samples within single hosts as well as between hosts. Most likely due to stochastic effects, we did not observe clear instances of selection for specific DVGs or for shorter DVGs over the course of infection. Furthermore, DVG presence was not found to be associated with peak viral titer or peak symptom scores. Our analyses highlight the diversity of DVG populations within a host over the course of infection and the apparent role that genetic drift plays in their population dynamics.

Importance

The evolution of influenza virus, in terms of single nucleotide variants and the reassortment of gene segments, has been studied in detail. However, influenza is known to generate defective viral genomes (DVGs) during replication, and little is known about how these genomes evolve both within hosts and at the population level. Studies in animal models have indicated that prophylactically or therapeutically administered DVGs can impact patterns of disease progression. However, the formation of naturally-occurring DVGs, their evolutionary dynamics, and their contribution to disease severity in human hosts is not well understood. Here, we identify the formation ofde novoDVGs in samples from human challenge studies throughout the course of infection. We analyze their evolutionary trajectories, revealing the important role of genetic drift in shaping DVG populations during acute infections with well-adapted viral strains.
Simultaneous X-ray radiography and diffraction topography imaging applied to silicon for defect analysis during melting and crystallization
Authors: Becker Maike , Regula Gabrielle , Reinhart Guillaume , Boller Elodie , Valade Jean-Paul , Rack Alexander , Tafforeau Paul , Mangelinck-Noël Nathalie
Published: October 2019

One of the key issues to be resolved to improve the performance of silicon solar cells is to reduce crystalline defect formation and propagation during the growth-process fabrication step. For this purpose, the generation of structural defects such as grain boundaries and dislocations in silicon must be understood and characterized. Here, in situ X-ray diffraction imaging, historically named topography, is combined with radiography imaging to analyse the development of crystal defects before, during and after crystallization. Two individual indirect detector systems are implemented to record simultaneously the crystal structure (topographs) and the solid–liquid morphology evolution (radiographs) at high temperature. This allows for a complete synchronization of the images and for an increased image acquisition rate compared with previous studies that used X-ray sensitive films to record the topographs. The experiments are performed with X-ray synchrotron radiation at beamline ID19 at the European Synchrotron Radiation Facility. In situ observations of the heating, melting, solidification and holding stages of silicon samples are presented, to demonstrate that with the upgraded setup detailed investigations of time-dependent phenomena are now possible. The motion of dislocations is recorded throughout the experiment, so that their interaction with grain boundaries and their multiplication through the activation of Frank–Read sources can be observed. Moreover, the capability to record with two camera-based detectors allows for the study of the relationship between strain distribution, twinning and nucleation events. In conclusion, the simultaneous recording of topographs and radiographs has great potential for further detailed investigations of the interaction and generation of grains and defects that influence the growth process and the final crystalline structure in silicon and other crystalline materials.
Light source based on a 100 mm-long monolithic undulator magnet with a very short 4 mm-period length
Authors: Yamamoto Shigeru , Kashiwagi Shigeru , Masuda Shinichi , Nakanii Nobuhiko , Hosokai Tomonao , Kando Masaki , Muto Toshiya , Nanbu Ken-ichi , Hinode Fujio , Hama Hiroyuki
Published: October 2019

A novel method to fabricate undulator magnets of a-few-millimetre-period length is being explored. Plate-type magnets, 100 mm-long with 4 mm-period length, have been successfully fabricated. They produce an undulator field of approximately 3 kG at a gap of 1.6 mm. Prototype undulators based on this technology have been constructed. Field measurements and characterization show that the quality of the undulator field of these plate magnets is sufficient for an undulator light source, and the calculated spectrum shows that the fundamental radiation emitted from this field is quite satisfactory. Test experiments for light generation using a real electron beam have been carried out at a test accelerator at the Research Center for Electron Photon Science (ELPH), Tohoku University, Japan, which is able to realize optics conditions to accept a very short gap of ∼1.6 mm. First observation and characterization of blue light was successfully accomplished.
Time-resolved X-ray absorption spectroelectrochemistry of redox active species in solution
Authors: Cheaib Khaled , Maurice Baptiste , Mateo Tiphaine , Halime Zakaria , Lassalle-Kaiser Benedikt
Published: October 2019

Electrochemistry and electrocatalysis have been receiving increased attention recently due to their crucial contribution to electrical-to-chemical conversion systems. We describe here the development and operation of a new spectroelectrochemical transmission cell for time-resolved X-ray absorption spectroscopy of solutions. X-ray absorption spectra were recorded on the ROCK beamline of SOLEIL under constant and scanning potentials. Spectra were recorded at a frequency of 2 Hz during a cyclic voltammetry experiment performed on a 20 mM solution of FeIIICl3·6H2O at 20 mV s−1 scanning speed. Spectra with good signal-to-noise ratios were obtained when averaging ten spectra over 5 s, corresponding to a 100 mV potential range. A 90% conversion rate from Fe(III) to Fe(II) was spectroscopically demonstrated in cyclic voltammetry mode.
Crystal structure, Hirshfeld surface analysis and interaction energy and DFT studies of (2Z)-4-benzyl-2-(2,4-dichlorobenzylidene)-2H-1,4-benzothiazin-3(4H)-one
Authors: Sebbar Nada Kheira , Hni Brahim , Hökelek Tuncer , Labd Taha Mohamed , Mague Joel T. , El Ghayati Lhoussaine , Essassi El Mokhtar
Published: October 2019

The title compound, C22H15Cl2NOS, contains 1,4-benzothiazine and 2,4-dichlorobenzylidene units, where the dihydrothiazine ring adopts a screw-boat conformation. In the crystal, intermolecular C—HBnz...OThz(Bnz = benzene and Thz = thiazine) hydrogen bonds form corrugated chains extending along theb-axis direction which are connected into layers parallel to thebcplane by intermolecular C—HMethy...SThz(Methy = methylene) hydrogen bonds, enclosingR44(22) ring motifs. Offset π-stacking interactions between 2,4-dichlorophenyl rings [centroid–centroid = 3.7701 (8) Å] and π-interactions which are associated by C—HBnz...π(ring) and C—HDchlphy...π(ring) (Dchlphy = 2,4-dichlorophenyl) interactions may be effective in the stabilization of the crystal structure. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (29.1%), H...C/C...H (27.5%), H...Cl/Cl...H (20.6%) and O...H/H...O (7.0%) interactions. Hydrogen-bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that in the crystal, the C—HBnz...OThzand C—HMethy...SThzhydrogen-bond energies are 55.0 and 27.1 kJ mol−1, respectively. Density functional theory (DFT) optimized structures at the B3LYP/6-311G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.
Crystal structures and Hirshfeld surface analyses of 4-benzyl-6-phenyl-4,5-dihydropyridazin-3(2H)-one and methyl 2-[5-(2,6-dichlorobenzyl)-6-oxo-3-phenyl-1,4,5,6-tetrahydropyridazin-1-yl]acetate
Authors: Dadou Said , Kansiz Sevgi , Daoui Said , El Kalai Fouad , Baydere Cemile , Saddik Rafik , Karrouchi Khalid , Dege Necmi , Benchat Noureddine
Published: October 2019

The asymmetric units of the title compounds both contain one nonplanar molecule. In 4-benzyl-6-phenyl-4,5-dihydropyridazin-3(2H)-one, C17H14N2O, (I), the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 46.69 (9)°; the phenyl ring of the benzyl group is nearly perpendicular to the plane of the pyridazine ring, the dihedral angle being 78.31 (10)°. In methyl 2-[5-(2,6-dichlorobenzyl)-6-oxo-3-phenyl-1,4,5,6-tetrahydropyridazin-1-yl]acetate, C20H16Cl2N2O3, (II), the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 21.76 (18)°, whereas the phenyl ring of the dichlorobenzyl group is inclined to the pyridazine ring by 79.61 (19)°. In the crystal structure of (I), pairs of N—H...O hydrogen bonds link the molecules into inversion dimers with an R
2
2(8) ring motif. In the crystal structure of (II), C—H...O hydrogen bonds generate dimers with R
1
2(7), R
2
2(16) and R
2
2(18) ring motifs. The Hirshfeld surface analyses of compound (I) suggests that the most significant contributions to the crystal packing are by H...H (48.2%), C...H/H...C (29.9%) and O...H/H...O (8.9%) contacts. For compound (II), H...H (34.4%), C...H/H...C (21.3%) and O...H/H...O (16.5%) interactions are the most important contributions.
Crystal structure, Hirshfeld surface analysis and interaction energy and DFT studies of methyl 4-[3,6-bis(pyridin-2-yl)pyridazin-4-yl]benzoate
Authors: Filali Mouad , El Ghayati Lhoussaine , Hökelek Tuncer , Mague Joel T. , Ben-Tama Abdessalam , El Hadrami El Mestafa , Sebbar Nada Kheira
Published: October 2019

The title compound, C22H16N4O2, contains two pyridine rings and one methoxycarbonylphenyl group attached to a pyridazine ring which deviates very slightly from planarity. In the crystal, ribbons consisting of inversion-related chains of molecules extending along the a-axis direction are formed by C—HMthy...OCarbx (Mthy = methyl and Carbx = carboxylate) hydrogen bonds. The ribbons are connected into layers parallel to the bc plane by C—HBnz...π(ring) (Bnz = benzene) interactions. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (39.7%), H...C/C...H (27.5%), H...N/N...H (15.5%) and O...H/H...O (11.1%) interactions. Hydrogen-bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that in the crystal, C—HMthy...OCarbx hydrogen-bond energies are 62.0 and 34.3 kJ mol−1, respectively. Density functional theory (DFT) optimized structures at the B3LYP/6-311G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.
Crystal structure, synthesis and thermal properties of bis(acetonitrile-κN)bis(4-benzoylpyridine-κN)bis(isothiocyanato-κN)nickel(II)
Authors: Wellm Carsten , Näther Christian
Published: October 2019

In the crystal structure of the title compound, [Ni(NCS)2(CH3CN)2(C12H9NO)2] or Ni(NCS)2(4-benzoylpyridine)2(acetonitrile)2, the NiII ions are octahedrally coordinated by the N atoms of two thiocyanate anions, two 4-benzoylpyridine ligands and two acetonitrile molecules into discrete complexes that are located on centres of inversion. In the crystal, the discrete complexes are linked by centrosymmetric pairs of weak C—H...S hydrogen bonds into chains. Thermogravimetric measurements prove that, upon heating, the title complex loses the two acetonitrile ligands and transforms into a new crystalline modification of the chain compound [Ni(NCS)2(4-benzoylpyridine)2], which is different from that of the corresponding CoII, NiII and CdII coordination polymers reported in the literature. IR spectroscopic investigations indicate the presence of bridging thiocyanate anions but the powder pattern cannot be indexed and, therefore, this structure is unknown.
Crystal structure of a 1:1 cocrystal of nicotinamide with 2-chloro-5-nitrobenzoic acid
Authors: Bairagi Keshab M. , Pal Priyanka , Bhandary Subhrajyoti , Venugopala Katharigatta N. , Chopra Deepak , Nayak Susanta K.
Published: October 2019

In the title 1:1 cocrystal, C7H4ClNO4·C6H6N2O, nicotinamide (NIC) and 2-chloro-5-nitrobenzoic acid (CNBA) cocrystallize with one molecule each of NIC and CNBA in the asymmetric unit. In this structure, CNBA and NIC form hydrogen bonds through O—H...N, N—H...O and C—H...O interactions along with N—H...O dimer hydrogen bonds of NIC. Further additional weak π–π interactions stabilize the molecular assembly of this cocrystal.
Crystal structure and Hirshfeld surface analysis of 2-(4-nitrophenyl)-2-oxoethyl benzoate
Authors: Sheshadri S. N. , Chidan Kumar C. S. , Naveen S. , Veeraiah M. K. , Raghava Reddy Kakarla , Warad Ismail
Published: October 2019

The title compound, C15H11NO5, is relatively planar, with the planes of the two aromatic rings being inclined to each other by 3.09 (5)°. In the crystal, molecules are linked by a pair of C—H...O hydrogen bonds, forming inversion dimers, which enclose an R
2
2(16) ring motif. The dimers are linked by a further pair of C—H...O hydrogen-bonds forming ribbons enclosing R
4
4(26) ring motifs. The ribbons are linked by offset π–π interactions [centroid–centroid distances = 3.6754 (6)–3.7519 (6) Å] to form layers parallel to the ac plane. Through Hirshfeld surface analyses, the d
norm surfaces, electrostatic potential and two-dimensional fingerprint (FP) plots were examined to verify the contributions of the different intermolecular contacts within the supramolecular structure. The shape-index surface shows that two sides of the molecule are involved with the same contacts in neighbouring molecules, and the curvedness plot shows flat surface patches that are characteristic of planar stacking.