bluuebunny/crossref_metadata_2025 huggingface dataset:
What God has Joined Together: Family Formation and Religion among Young Adults
Authors: Denton Melinda Lundquist , Uecker Jeremy E.
Published: October 2017

This study considers how family transitions influence future religiosity among young adults and demonstrates that both marriage and parenthood can serve to reinforce religious commitment among those who are religiously engaged. Drawing on data from the National Study of Youth and Religion, we look at religious change between Wave 3 (18–24 years old) and Wave 4 (23–28 years old) and how this varies across six family statuses: Married with Children, Married without Children, Cohabiting with Children, Cohabiting without Children, Single with Children and Single without Children. We find greater future religious engagement among married individuals compared to those who are single or cohabiting, regardless of the presence of children. Among single and cohabiting parents, however, the presence of children is associated with greater religious salience, though not with attendance at religious services. The findings demonstrate a continued link between the institutions of family and religion at a time when ties to both institutions are loosening.
Transcriptome assembly strategies for precision medicine
Authors: Wang Lu , Acharya Lipi , Bai Changxin , Zhu Dongxiao
Published: October 2017

Background

Precision medicine approach holds great promise to tailored diagnosis, treatment and prevention. Individuals can be vastly different in their genomic information and genetic mechanisms hence having unique transcriptomic signatures. The development of precision medicine has
demanded moving beyond DNA sequencing (DNA‐Seq) to much more pointed RNA‐sequencing (RNA‐Seq) [ Cell, 2017, 168: 584–599].

Results

Here we conduct a brief survey on the recent methodology development of transcriptome assembly approach using RNA‐Seq.

Conclusions

Since transcriptomes in human disease are highly complex, dynamic and diverse, transcriptome assembly is playing an increasingly important role in precision medicine research to dissect the molecular mechanisms of the human diseases.
An unambiguous definition of the Froude number for lee waves in the deep ocean
Authors: Mayer F. T. , Fringer O. B.
Published: October 2017

There is a long-standing debate in the literature of stratified flows over topography concerning the correct dimensionless number to refer to as a Froude number. Common definitions using external quantities of the flow include$U/(ND)$,$U/(Nh_{0})$, and$Uk/N$, where$U$and$N$are, respectively, scales for the background velocity and buoyancy frequency,$D$is the depth, and$h_{0}$and$k^{-1}$are, respectively, height and width scales of the topography. It is also possible to define an internal Froude number$Fr_{\unicode[STIX]{x1D6FF}}=u_{0}/\sqrt{g^{\prime }\unicode[STIX]{x1D6FF}}$, where$u_{0}$,$g^{\prime }$, and$\unicode[STIX]{x1D6FF}$are, respectively, the characteristic velocity, reduced gravity, and vertical length scale of the perturbation above the topography. For the case of hydrostatic lee waves in a deep ocean, both$U/(ND)$and$Uk/N$are insignificantly small, rendering the dimensionless number$Nh_{0}/U$the only relevant dynamical parameter. However, although it appears to be an inverse Froude number, such an interpretation is incorrect. By non-dimensionalizing the stratified Euler equations describing the flow of an infinitely deep fluid over topography, we show that$Nh_{0}/U$is in fact the square of the internal Froude number because it can identically be written in terms of the inner variables,$Fr_{\unicode[STIX]{x1D6FF}}^{2}=Nh_{0}/U=u_{0}^{2}/(g^{\prime }\unicode[STIX]{x1D6FF})$. Our scaling also identifies$Nh_{0}/U$as the ratio of the vertical velocity scale within the lee wave to the group velocity of the lee wave, which we term the vertical Froude number,$Fr_{vert}=Nh_{0}/U=w_{0}/c_{g}$. To encapsulate such behaviour, we suggest referring to$Nh_{0}/U$as the lee-wave Froude number,$Fr_{lee}$.
Transatlantic Contrafacta, Musical Formats, and the Creation of Political Culture in Revolutionary America
Authors: GOODMAN GLENDA
Published: October 2017

This article investigates Revolutionary-era American political culture through contrafacta of the British anthem “God Save the King.” Before, during, and after the Revolution the tune was frequently set with new lyrics that addressed political topics. The formats through which the song circulated (it was disseminated widely in manuscript and print), shaped the meaning and reception of these various contrafacta. Tracking “God Save the King” through the eighteenth century reveals how the United States remained connected to Britain, even when the lyrics—and the goals of the Revolution—repudiated that bond. Song versions also provide a musical map of the fragmenting political landscape of the early Republic. Ultimately, the diversity of the formats and the song versions reveal the ambivalent relationship between postcolonial United States and Britain, as well as the diversity of political culture within the United States.
“Yes, [Gospel] Is Real”: Half a Century with Chicago's Martin and Morris Company
Authors: NORTON KAY
Published: October 2017

The Martin and Morris Music Studio (MMMS) imprint permeated the first fifty years of black gospel music. Jointly owned by singer/impresaria Sallie Martin (1895/6–1988) and composer/arranger/pianist/organist Kenneth Morris (1917–88), the MMMS delivered gospel songs to an eager public and offered ordinary Americans the chance to see their names in print as author or composer on the cover of a gospel octavo, copies of which could then be sold to benefit that same ordinary American. Their influence extended far beyond that service, however. Martin and her Singers performed and popularized music bearing the MMMS imprint in venues ranging from small churches in the Deep South to national conventions in Washington, D.C., and widened circulation of MMMS music via Los Angeles recording studios. The unprecedented accomplishments of the MMMS, active from 1940 to 1993, have not been fully explored. Relying on transcribed interviews of the owners by Bernice Johnson Reagon, James Standifer, and others, accounts in historical newspapers, and company archives, this article addresses that void. The centrality of the MMMS in twentieth-century gospel of all types is clarified through examination of contexts for black-owned music publishing in the last century, the owners’ early business models, and their changing roles in the creation, publication, popularization, and dissemination of gospel music for more than fifty years.
Performing Catfish Row in the Soviet Union: The Everyman Opera Company andPorgy and Bess, 1955–56
Authors: UY MICHAEL SY
Published: October 2017

For three weeks in 1955 and 1956 the Everyman Opera Company stagedPorgy and Bessin Leningrad and Moscow. In the previous two years, the Robert Breen and Blevins Davis production of Gershwin's opera had toured Europe and Latin America, funded by the U.S. State Department. Yet when Breen negotiated a performance tour to Russia, the American government denied funding, stating, among other reasons, that a production would be “politically premature.” Surprisingly, however, the opera was performed with the Soviet Ministry of Culture paying the tour costs in full. I argue that this tour, negotiated amid the growing civil rights movement, was a non-paradigmatic example of cultural exchange at the beginning of the Cold War: an artistic product funded at different times byboththe United Statesandthe Soviet Union. Through an examination of the tour's archival holdings, interviews with surviving cast members, and the critical reception in the historically black press, this essay contributes to ongoing questions of Cold War scholarship, including discussions on race, identity, and the unpredictable nature of cultural exchange.
Financial Sector Workers' Experiences of Managing Suicidal Clients
Authors: O'Neill Siobhan , Ennis Edel , McFeeters Danielle , Gallagher Lia
Published: October 2017

Abstract. Background: Financial sector workers interface with indebted clients, who may be distressed and have heightened vulnerability to suicidality. Aim(s): This study examined the experiences of 10 Irish financial sector workers who had experiences of encountering distressed clients who discuss suicide. Method: Semistructured interviews (open-ended questions) were used. Results: Interpretative phenomenological analysis (IPA) identified four themes, namely: (1) avoidance versus confrontation of reality (management of the debt); (2) role conflict (recovering the debt vs. supporting the client); (3) emotional impact and distancing from clients (coping with concerns for client welfare); (4) desire for support (practical and emotional training and support needs). Limitations: The frequency with which such clients were encountered was not assessed. Conclusion: These themes demonstrate the need to provide support to this group, and also the difficulties in providing training to manage suicidal clients in a context where the staff member's goal is to recover debt.
Appropriate Targets for Search Advertising as Part of Online Gatekeeping for Suicide Prevention
Authors: Sueki Hajime , Ito Jiro
Published: October 2017

Abstract. Background: Gatekeeper training is an effective suicide prevention strategy. However, the appropriate targets of online gatekeeping have not yet been clarified. Aim: We examined the association between the outcomes of online gatekeeping using the Internet and the characteristics of consultation service users. Method: An advertisement to encourage the use of e-mail-based psychological consultation services among viewers was placed on web pages that showed the results of searches using suicide-related keywords. All e-mails received between October 2014 and December 2015 were replied to as part of gatekeeping, and the obtained data (responses to an online questionnaire and the content of the received e-mails) were analyzed. Results: A total of 154 consultation service users were analyzed, 35.7% of whom were male. The median age range was 20–29 years. Online gatekeeping was significantly more likely to be successful when such users faced financial/daily life or workplace problems, or revealed their names (including online names). By contrast, the activity was more likely to be unsuccessful when it was impossible to assess the problems faced by consultation service users. Conclusion: It may be possible to increase the success rate of online gatekeeping by targeting individuals facing financial/daily life or workplace problems with marked tendencies for self-disclosure.
Highly structured prokaryote communities exist within the skeleton of coral colonies
Authors: Marcelino Vanessa R , van Oppen Madeleine J H , Verbruggen Heroen
Published: October 2017

Physiological performance, disease and bleaching prevalence are often patchy within individual coral colonies. These responses are largely influenced by coral-associated microbes, but how the coral microbiome changes over small spatial scales has never been quantified before. We performed a high-resolution quantification of the spatial scale of microbial species turnover (β-diversity) within skeletons of boulder-forming Porites corals. We found very strong prokaryotic species turnover across spatial scales ranging from 4 mm to 2 m within individual colonies, possibly resulting from dispersal limitation and microbial interactions. The microalgal community was more homogeneously distributed, which is likely due to these photosymbionts actively boring through limestone. Our findings highlight unprecedented levels of intra-colony heterogeneity in the skeletal microbiome, which has implications for the experimental design of coral microbiome studies and for our understanding of coral resilience.
The plant circadian clock influences rhizosphere community structure and function
Authors: Hubbard Charley J , Brock Marcus T , van Diepen Linda T A , Maignien Loïs , Ewers Brent E , Weinig Cynthia
Published: October 2017

Plants alter chemical and physical properties of soil, and thereby influence rhizosphere microbial community structure. The structure of microbial communities may in turn affect plant performance. Yet, outside of simple systems with pairwise interacting partners, the plant genetic pathways that influence microbial community structure remain largely unknown, as are the performance feedbacks of microbial communities selected by the host plant genotype. We investigated the role of the plant circadian clock in shaping rhizosphere community structure and function. We performed 16S ribosomal RNA gene sequencing to characterize rhizosphere bacterial communities of Arabidopsis thaliana between day and night time points, and tested for differences in community structure between wild-type (Ws) vs clock mutant (toc1-21, ztl-30) genotypes. We then characterized microbial community function, by growing wild-type plants in soils with an overstory history of Ws, toc1-21 or ztl-30 and measuring plant performance. We observed that rhizosphere community structure varied between day and night time points, and clock misfunction significantly altered rhizosphere communities. Finally, wild-type plants germinated earlier and were larger when inoculated with soils having an overstory history of wild-type in comparison with clock mutant genotypes. Our findings suggest the circadian clock of the plant host influences rhizosphere community structure and function.
Stress response of a marine ammonia-oxidizing archaeon informs physiological status of environmental populations
Authors: Qin Wei , Amin Shady A , Lundeen Rachel A , Heal Katherine R , Martens-Habbena Willm , Turkarslan Serdar , Urakawa Hidetoshi , Costa Kyle C , Hendrickson Erik L , Wang Tony , Beck David A C , Tiquia-Arashiro Sonia M , Taub Fred , Holmes Andrew D , Vajrala Neeraja , Berube Paul M , Lowe Todd M , Moffett James W , Devol Allan H , Baliga Nitin S , Arp Daniel J , Sayavedra-Soto Luis A , Hackett Murray , Armbrust E Virginia , Ingalls Anitra E , Stahl David A
Published: October 2017

High representation by ammonia-oxidizing archaea (AOA) in marine systems is consistent with their high affinity for ammonia, efficient carbon fixation, and copper (Cu)-centric respiratory system. However, little is known about their response to nutrient stress. We therefore used global transcriptional and proteomic analyses to characterize the response of a model AOA, Nitrosopumilus maritimus SCM1, to ammonia starvation, Cu limitation and Cu excess. Most predicted protein-coding genes were transcribed in exponentially growing cells, and of ~74% detected in the proteome, ~6% were modified by N-terminal acetylation. The general response to ammonia starvation and Cu stress was downregulation of genes for energy generation and biosynthesis. Cells rapidly depleted transcripts for the A and B subunits of ammonia monooxygenase (AMO) in response to ammonia starvation, yet retained relatively high levels of transcripts for the C subunit. Thus, similar to ammonia-oxidizing bacteria, selective retention of amoC transcripts during starvation appears important for subsequent recovery, and also suggests that AMO subunit transcript ratios could be used to assess the physiological status of marine populations. Unexpectedly, cobalamin biosynthesis was upregulated in response to both ammonia starvation and Cu stress, indicating the importance of this cofactor in retaining functional integrity during times of stress.
Harnessing mechanical instabilities at the nanoscale to achieve ultra-low stiffness metals
Authors: Reeve Samuel Temple , Belessiotis-Richards Alexis , Strachan Alejandro
Published: October 2017

Alloy and microstructure optimization have led to impressive improvements in the strength of engineering metals, while the range of Young’s moduli achievable has remained essentially unchanged. This is because stiffness is insensitive to microstructure and bounded by individual components in composites. Here we design ultra-low stiffness in fully dense, nanostructured metals via the stabilization of a mechanically unstable, negative stiffness state of a martensitic alloy by its coherent integration with a compatible, stable second component. Explicit large-scale molecular dynamics simulations of the metamaterials with state of the art potentials confirm the expected ultra-low stiffness while maintaining full strength. We find moduli as low as 2 GPa, a value typical of soft materials and over one order of magnitude lower than either constituent, defying long-standing composite bounds. Such properties are attractive for flexible electronics and implantable devices. Our concept is generally applicable and could significantly enhance materials science design space.
Characterization of histone acylations links chromatin modifications with metabolism
Authors: Simithy Johayra , Sidoli Simone , Yuan Zuo-Fei , Coradin Mariel , Bhanu Natarajan V. , Marchione Dylan M. , Klein Brianna J. , Bazilevsky Gleb A. , McCullough Cheryl E. , Magin Robert S. , Kutateladze Tatiana G. , Snyder Nathaniel W. , Marmorstein Ronen , Garcia Benjamin A.
Published: October 2017

Over the last decade, numerous histone acyl post-translational modifications (acyl-PTMs) have been discovered, of which the functional significance is still under intense study. Here, we use high-resolution mass spectrometry to accurately quantify eight acyl-PTMs in vivo and after in vitro enzymatic assays. We assess the ability of seven histone acetyltransferases (HATs) to catalyze acylations on histones in vitro using short-chain acyl-CoA donors, proving that they are less efficient towards larger acyl-CoAs. We also observe that acyl-CoAs can acylate histones through non-enzymatic mechanisms. Using integrated metabolomic and proteomic approaches, we achieve high correlation (R2 > 0.99) between the abundance of acyl-CoAs and their corresponding acyl-PTMs. Moreover, we observe a dose-dependent increase in histone acyl-PTM abundances in response to acyl-CoA supplementation in in nucleo reactions. This study represents a comprehensive profiling of scarcely investigated low-abundance histone marks, revealing that concentrations of acyl-CoAs affect histone acyl-PTM abundances by both enzymatic and non-enzymatic mechanisms.
Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway
Authors: Marini Cecilia , Bruno Silvia , Fiz Francesco , Campi Cristina , Piva Roberta , Cutrona Giovanna , Matis Serena , Nieri Alberto , Miglino Maurizio , Ibatici Adalberto , Maria Orengo Anna , Maria Massone Anna , Neumaier Carlo Emanuele , Totero Daniela de , Giannoni Paolo , Bauckneht Matteo , Pennone Michele , Tenca Claudya , Gugiatti Elena , Bellini Alessandro , Borra Anna , Tedone Elisabetta , Efetürk Hülya , Rosa Francesca , Emionite Laura , Cilli Michele , Bagnara Davide , Brucato Valerio , Bruzzi Paolo , Piana Michele , Fais Franco , Sambuceti Gianmario
Published: October 2017

Skeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone.
A method for the unbiased and efficient segmental labelling of RNA-binding proteins for structure and biophysics
Authors: Gallagher Christopher , Burlina Fabienne , Offer John , Ramos Andres
Published: October 2017

Most eukaryotic RNA regulators recognise their RNA and protein partners by the combinatorial use of several RNA binding domains. Inter-domain dynamics and interactions play a key role in recognition and can be analysed by techniques such as NMR or FRET, provided that the information relative to the individual interactions can be de-convoluted. Segmentally labelling the proteins by ligating labelled and unlabelled peptide chains allows one to filter out unwanted information and observe the labelled moieties only. Several strategies have been implemented to ligate two protein fragments, but multiple ligations, which are necessary to segmentally label proteins of more than two domains, are more challenging and often dependent on the structure and solubility of the domains. Here we report a method to ligate multiple protein segments that allows the fast, high yield labelling of both internal and end domains, depending on the requirements. We use TCEP and mercaptophenylacetic acid (MPAA) in an optimised reaction environment to achieve an efficient ligation of protein domains independently from their structure or solubility. We expect the method will provide a useful tool for the molecular study of combinatorial protein–RNA recognition in RNA regulation.
Between-days intra-rater reliability with a hand held myotonometer to quantify muscle tone in the acute stroke population
Authors: Lo Wai Leung Ambrose , Zhao Jiang Li , Chen Ling , Lei Di , Huang Dong Feng , Tong Kin Fai
Published: October 2017

A myotonometer can objectively quantify changes in muscle tone. The between-days intra-rater reliability in a ward setting for the acute stroke population remains unknown. This study aimed to investigate the device’s between-days intra-rater reliability when used in a ward setting for acute stroke participants. Muscle tone of biceps brachii, brachioradialis, rectus femoris, and tibialis anterior was recorded in the ward at bedside by one physiotherapist on two consecutive days. This study included participants who were within 1 month of their first stroke occurrence. Participants who were medically unstable or who suffered from brain stem injury were excluded. Reliability was assessed by the intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), and the Bland-Altman limits of agreement. The results indicated excellent between-days intra-rater reliability (ICC > 0.75). SEM and SRD show small differences between measurements. The Bland-Altman analysis indicated a tendency of overestimation of the rectus femoris. MyotonPRO demonstrated acceptable reliability when used in a ward setting in those patients with acute stroke. However, results should be interpreted with caution, due to the limitations of the study and the varying level of consistency observed between different muscles.
The characteristics of adjacent anatomy of mandibular third molar germs: a CBCT study to assess the risk of extraction
Authors: Sun Rui , Cai Yu , Yuan Yi , Zhao Ji-Hong
Published: October 2017

This study aims to investigate the characteristics of adjacent anatomy of mandibular third molar germs (MTMGs). Three hundred Chinese patients aged 12 to 17 years old who received cone-beam computed tomography (CBCT) were enrolled. The continuity of cortical outline of inferior alveolar canals (IACs) in the region of MTMGs, the integrity of lingual bone cortex and the relationship between hard tissue part of MTMGs and IACs were investigated by observing CBCT data via the NNT viewer software. The age, degree of dental development, gender and location were recorded as variables. The associations between different variables and the observed data were analysed. The possibilities of disrupted cortical outline of IACs or the hard tissue part of MTMGs contacting IACs were significantly lower in 12 or 13 age groups, lower in Nolla stage ≤ 6. Males were significantly less than females in the incidence of disrupted cortical outline of IACs. As to the perforation of lingual bone cortex, no significant differences were observed in gender, ages, location or development stages. According to the CBCT images, anatomical factors contributed the lest to the risk of inferior alveolar nerve and lingual nerve injury in the 12 to 13 age group during removing the MTMG removal.
Positive impact of the participation in the ENCHANTED trial in reducing Door-to-Needle Time
Authors: Yang Jie , Wang Xia , Yu Jian ping , Hang Jing , Lavados Pablo , Robinson Thompson , Arima Hisatomi , Lindley Richard I. , Anderson Craig S. , Chalmers John
Published: October 2017

Door-to-needle time (DNT) is a key performance indicator for efficient use of intravenous thrombolysis in acute ischemic stroke (AIS). We aimed to determine whether DNT improved over time in the Enhanced Control of Hypertension and Acute Stroke Study (ENCHANTED) and the clinical predictors of DNT. Temporal trends in DNT were assessed across fourths of time since activation of study centers using generalized linear model. Predictors of long DNT (>60 min) were determined in logistic regression models. Overall mean DNT (min) was 71.8 (95% confidence interval [CI] 70.4–73.2), but decreased significantly over time (fourths): 77.9 (74.9–80.9), 69.3 (66.7–72.0), 69.1 (66.5–71.8) and 71.4 (68.7–74.2) (P for trend, 0.003). The reduction in DNT was particularly marked in China (P for trend, 0.001), but was not significant across the other participating countries (P for trend, 0.065). Independent predictors of long DNT were recruitment from China, short onset-to-door time, lower numbers of patients treated per center, higher diastolic blood pressure, off-hour admission, and absence of proximal clot occlusion. DNT in ENCHANTED declined progressively during the trial, especially in China. However, DNT in China is still longer than the key performance parameter of ≤60 minutes recommended in guidelines. Effective national programs are needed to improve DNT in China.
Nonlinear magnetoelectric effect in paraelectric state of Co4Nb2O9 single crystal
Authors: Cao Yiming , Deng Guochu , Beran Přemysl , Feng Zhenjie , Kang Baojuan , Zhang Jincang , Guiblin Nicolas , Dkhil Brahim , Ren Wei , Cao Shixun
Published: October 2017

We report the structural, magnetoelectric (ME), magnetic and electric control of magnetic properties in Co4Nb2O9 (CNO) single crystal. A detailed ME measurement reveals a nonlinear ME effect instead of a linear ME effect in CNO single crystal. By fitting the magnetization-electric field (M-E) curve, it can be found that the linear ($${\alpha }_{e}$$

α

e

) and quadratic (γ) coefficients equal to ~8.27 ps/m and ~−6.46 ps/MV for upper branch, as well as ~8.38 ps/m and ~6.75 ps/MV for the lower branch. More importantly, a pronounced response was observed under a small cooling magnetic field, which cannot even cause the spin flop. This suggests a magnetoelectric effect can occur at paraelectric state for CNO single crystal. Furthermore, we also found that the magnetization of every axis responds to electric field applied along a-axis, but fails to do so when the electric field is applied c-axis. Such findings supply a direct evidence to the magnetic structure and ME coupling mechanism indirectly reflected by our neutron experiment.
Neurofilament light protein in CSF and blood is associated with neurodegeneration and disease severity in Huntington’s disease R6/2 mice
Authors: Soylu-Kucharz Rana , Sandelius Åsa , Sjögren Marie , Blennow Kaj , Wild Edward J. , Zetterberg Henrik , Björkqvist Maria
Published: October 2017

There is an unmet need to reliably and non-invasively monitor disease progression in preclinical Huntington’s disease (HD) models. As a marker of axonal damage, neurofilament light chain (NfL) has been suggested a marker for neurodegeneration. NfL concentrations in blood and CSF were recently shown to have prognostic value for clinical HD progression and brain atrophy. We therefore hypothesized that CSF and blood NfL concentrations could be useful preclinical HD markers, reflecting underlying pathology. To test our hypothesis we utilized the R6/2 mouse model of HD and measured NfL concentrations in CSF and serum using the ultrasensitive Single molecule array (Simoa) platform. In addition, we assessed HD mouse disease characteristics. We found robust increases of NfL in CSF and serum in R6/2 mice compared to wild-type littermates. CSF and serum concentrations of NfL were significantly correlated, suggesting similar marker potential of serum NfL. CSF and serum concentrations of NfL correlated with disease severity, as assessed by striatal volume and body weight loss. We here provide evidence that CSF and blood NfL concentrations can be used as accessible and reliable pre-clinical HD markers. This will be of potential use for monitoring HD mouse model disease progression and evaluating preclinical disease-modifying treatment response.
Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells
Authors: Nakamura Yuki , Umeki Nobuhisa , Abe Mitsuhiro , Sako Yasushi
Published: October 2017

Noonan syndrome (NS) is a congenital hereditary disorder associated with developmental and cardiac defects. Some patients with NS carry mutations in SOS, a guanine nucleotide exchange factor (GEF) for the small GTPase RAS. NS mutations have been identified not only in the GEF domain, but also in various domains of SOS, suggesting that multiple mechanisms disrupt SOS function. In this study, we examined three NS mutations in different domains of SOS to clarify the abnormality in its translocation to the plasma membrane, where SOS activates RAS. The association and dissociation kinetics between SOS tagged with a fluorescent protein and the living cell surface were observed in single molecules. All three mutants showed increased affinity for the plasma membrane, inducing excessive RAS signalling. However, the mechanisms by which their affinity was increased were specific to each mutant. Conformational disorder in the resting state, increased probability of a conformational change on the plasma membrane, and an increased association rate constant with the membrane receptor are the suggested mechanisms. These different properties cause the specific phenotypes of the mutants, which should be rescuable with different therapeutic strategies. Therefore, single-molecule kinetic analyses of living cells are useful for the pathological analysis of genetic diseases.
Impact of Wide-Ranging Nanoscale Chemistry on Band Structure at Cu(In, Ga)Se2 Grain Boundaries
Authors: Stokes Adam , Al-Jassim Mowafak , Diercks David , Clarke Amy , Gorman Brian
Published: October 2017

The relative chemistry from grain interiors to grain boundaries help explain why grain boundaries may be beneficial, detrimental or benign towards device performance. 3D Nanoscale chemical analysis extracted from atom probe tomography (APT) (10’s of parts-per-million chemical sensitivity and sub-nanometer spatial resolution) of twenty grain boundaries in a high-efficiency Cu(In, Ga)Se2solar cell shows the matrix and alkali concentrations are wide-ranging. The concentration profiles are then related to band structure which provide a unique insight into grain boundary electrical performance. Fluctuating Cu, In and Ga concentrations result in a wide distribution of potential barriers at the valence band maximum (VBM) (−10 to −160 meV) and the conduction band minimum (CBM) (−20 to −70 meV). Furthermore, Na and K segregation is not correlated to hampering donors, (In, Ga)Cuand VSe, contrary to what has been previously reported. In addition, Na and K are predicted to be n-type dopants at grain boundaries. An overall band structure at grain boundaries is presented.
Crystal Orientation Dependence of Gallium Nitride Wear
Authors: Zeng Guosong , Sun Wei , Song Renbo , Tansu Nelson , Krick Brandon A.
Published: October 2017

We explore how crystallographic order and orientation affect the tribological (friction and wear) performance of gallium nitride (GaN), through experiments and theory. Friction and wear were measured in every direction on the c-plane of GaN through rotary wear experiment. This revealed a strong crystallographic orientation dependence of the sliding properties of GaN; a 60° periodicity of wear rate and friction coefficient was observed. The origin of this periodicity is rooted in the symmetry presented in wurtzite hexagonal lattice structure of III-nitrides. The lowest wear rate was found as 0.6 × 10−7 mm3/Nm with <1$$\bar{1}$$

1
¯

00>, while the wear rate associated with <1$$\bar{2}$$

2
¯

10> had the highest wear rate of 1.4 × 10−7 mm3/Nm. On the contrary, higher friction coefficient can be observed along <1$$\bar{1}$$

1
¯

00> while lower friction coefficient always appeared along <1$$\bar{2}$$

2
¯

10>. We developed a simple molecular statics approach to understand energy barriers associated with sliding and material removal; this calculated change of free energy associated with sliding revealed that there were smaller energy barriers sliding along <1$$\bar{2}$$

2
¯

10> as compared to the <1$$\bar{1}$$

1
¯

00> direction.
From receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug-action
Authors: Nederpelt Indira , Kuzikov Maria , de Witte Wilbert E. A. , Schnider Patrick , Tuijt Bruno , Gul Sheraz , IJzerman Adriaan P. , de Lange Elizabeth C. M. , Heitman Laura H.
Published: October 2017

An important question in drug discovery is how to overcome the significant challenge of high drug attrition rates due to lack of efficacy and safety. A missing link in the understanding of determinants for drug efficacy is the relation between drug-target binding kinetics and signal transduction, particularly in the physiological context of (multiple) endogenous ligands. We hypothesized that the kinetic binding parameters of both drug and endogenous ligand play a crucial role in determining cellular responses, using the NK1 receptor as a model system. We demonstrated that the binding kinetics of both antagonists (DFA and aprepitant) and endogenous agonists (NKA and SP) have significantly different effects on signal transduction profiles, i.e. potency values, in vitro efficacy values and onset rate of signal transduction. The antagonistic effects were most efficacious with slowly dissociating aprepitant and slowly associating NKA while the combination of rapidly dissociating DFA and rapidly associating SP had less significant effects on the signal transduction profiles. These results were consistent throughout different kinetic assays and cellular backgrounds. We conclude that knowledge of the relationship between in vitro drug-target binding kinetics and cellular responses is important to ultimately improve the understanding of drug efficacy in vivo.
Keeping it complicated: Mitochondrial genome plasticity across diplonemids
Authors: Valach Matus , Moreira Sandrine , Hoffmann Steve , Stadler Peter F. , Burger Gertraud
Published: October 2017

Chromosome rearrangements are important drivers in genome and gene evolution, with implications ranging from speciation to development to disease. In the flagellate Diplonema papillatum (Euglenozoa), mitochondrial genome rearrangements have resulted in nearly hundred chromosomes and a systematic dispersal of gene fragments across the multipartite genome. Maturation into functional RNAs involves separate transcription of gene pieces, joining of precursor RNAs via trans-splicing, and RNA editing by substitution and uridine additions both reconstituting crucial coding sequence. How widespread these unusual features are across diplonemids is unclear. We have analyzed the mitochondrial genomes and transcriptomes of four species from the Diplonema/Rhynchopus clade, revealing a considerable genomic plasticity. Although gene breakpoints, and thus the total number of gene pieces (~80), are essentially conserved across this group, the number of distinct chromosomes varies by a factor of two, with certain chromosomes combining up to eight unrelated gene fragments. Several internal protein-coding gene pieces overlap substantially, resulting, for example, in a stretch of 22 identical amino acids in cytochrome c oxidase subunit 1 and NADH dehydrogenase subunit 5. Finally, the variation of post-transcriptional editing patterns across diplonemids indicates compensation of two adverse trends: rapid sequence evolution and loss of genetic information through unequal chromosome segregation.
Prolonged duration of nonequilibrated Dirac fermions in neutral topological insulators
Authors: Sumida K. , Ishida Y. , Zhu S. , Ye M. , Pertsova A. , Triola C. , Kokh K. A. , Tereshchenko O. E. , Balatsky A. V. , Shin S. , Kimura A.
Published: October 2017

Topological insulators (TIs) possess spin-polarized Dirac fermions on their surface but their unique properties are often masked by residual carriers in the bulk. Recently, (Sb1−x
Bi
x
)2Te3 was introduced as a non-metallic TI whose carrier type can be tuned from n to p across the charge neutrality point. By using time- and angle-resolved photoemission spectroscopy, we investigate the ultrafast carrier dynamics in the series of (Sb1−x
Bi
x
)2Te3. The Dirac electronic recovery of ∼10 ps at most in the bulk-metallic regime elongated to >400 ps when the charge neutrality point was approached. The prolonged nonequilibration is attributed to the closeness of the Fermi level to the Dirac point and to the high insulation of the bulk. We also discuss the feasibility of observing excitonic instability of (Sb1−x
Bi
x
)2Te3.
Determining the Quality Factor of Dielectric Ceramic Mixtures with Dielectric Constants in the Microwave Frequency Range
Authors: Chen Hetuo , Fu Xuewen , An Qi , Tang Bin , Zhang Shuren , Yang Hao , Long Yin , Harfouche Mark , Wang Huolei , Li Yingxiang
Published: October 2017

Microwave dielectric ceramic materials are extensively utilized in microwave applications because of their high dielectric constants and quality factors. These applications also require ceramics of zero temperature coefficients at the resonant frequency (τ
f
), which can be realized through mixing a ceramic that one is interested in with another ceramic with −τ
f
, or by performing the ionic substitution. With the mixing/ionic substitution, it is indispensable to compute the quality factors precisely. Previous study indicates that the quality factor depends on the grain size, porosity, internal strain, structure, phase evolution, and conductivity etc. Here we derive a quality factor formula based on the definition, which works very well for multiphase composites, single phase solid solutions, and equivalent ionic substituted single phase materials. Our formula calculation and fits to the previous experimental results demonstrate that the quality factor of the ceramic mixtures strongly depend on the dielectric constants and the dielectric constant variation index. Our results suggest that the impacts from grain size, porosity, and internal strain etc. can be summarized to the dielectric constant or dielectric constant variation index, which is of great importance for future design of high performance microwave dielectric ceramics.
Unravelling pathways downstream Sox6 induction in K562 erythroid cells by proteomic analysis
Authors: Barbarani Gloria , Ronchi Antonella , Ruoppolo Margherita , Santorelli Lucia , Steinfelder Robert , Elangovan Sudharshan , Fugazza Cristina , Caterino Marianna
Published: October 2017

The Sox6 transcription factor is crucial for terminal maturation of definitive red blood cells. Sox6-null mouse fetuses present misshapen and nucleated erythrocytes, due to impaired actin assembly and cytoskeleton stability. These defects are accompanied with a reduced survival of Sox6−/− red blood cells, resulting in a compensated anemia. Sox6-overexpression in K562 cells and in human primary ex vivo erythroid cultures enhances erythroid differentiation and leads to hemoglobinization, the hallmark of erythroid maturation. To obtain an overview on processes downstream to Sox6 expression, we performed a differential proteomic analysis on human erythroid K562 cells overexpressing Sox6. Sox6-overexpression induces dysregulation of 64 proteins, involved in cytoskeleton remodeling and in protein synthesis, folding and trafficking, key processes for erythroid maturation. Moreover, 43 out of 64 genes encoding for differentially expressed proteins contain within their proximal regulatory regions sites that are bound by SOX6 according to ENCODE ChIP-seq datasets and are possible direct SOX6 targets. SAR1B, one of the most induced proteins upon Sox6 overexpression, shares a conserved regulatory module, composed by a double SOX6 binding site and a GATA1 consensus, with the adjacent SEC24 A gene. Since both genes encode for COPII components, this element could concur to the coordinated expression of these proteins during erythropoiesis.
Improved performance of the artus Mycobacterium tuberculosis RG PCR kit in a low incidence setting: a retrospective monocentric study
Authors: Kohlmorgen Britta , Elias Johannes , Schoen Christoph
Published: October 2017

Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC) strains resistant against rifampin (RIF) and isoniazid (INH) pose a serious threat to global health. However, rapid and reliable MTBC detection along with RIF/INH susceptibility testing are challenging in low prevalence countries due to the higher rate of false positives. Here, we provide the first performance data for the artus MTBC PCR assay in a low prevalence setting. We analyze 1323 respiratory and 311 non-respiratory samples with the artus MTBC PCR assay as well as by mycobacterial culture and microscopy. We propose retesting of specimens in duplicate and consideration of a determined cycle-threshold value cut-off greater than 34, as this significantly increases accuracy, specificity, and negative predictive value without affecting sensitivity. Furthermore, we tested fourteen MTBC positive samples with the GenoType MTBDRplus test and demonstrate that using an identical DNA extraction protocol for both assays does not impair downstream genotypic testing for RIF and INH susceptibility. In conclusion, our procedure optimizes the use of the artus MTB assay with workload efficient methods in a low incidence setting. Combining the modified artus MTB with the GenoType MTBDRplus assays allows rapid and accurate detection of MTBC and RIF/INH resistance.
Reducing the critical particle diameter in (highly) asymmetric sieve-based lateral displacement devices
Authors: Dijkshoorn J. P. , Schutyser M. A. I. , Sebris M. , Boom R. M. , Wagterveld R. M.
Published: October 2017

Deterministic lateral displacement technology was originally developed in the realm of microfluidics, but has potential for larger scale separation as well. In our previous studies, we proposed a sieve-based lateral displacement device inspired on the principle of deterministic lateral displacement. The advantages of this new device is that it gives a lower pressure drop, lower risk of particle accumulation, higher throughput and is simpler to manufacture. However, until now this device has only been investigated for its separation of large particles of around 785 µm diameter. To separate smaller particles, we investigate several design parameters for their influence on the critical particle diameter. In a dimensionless evaluation, device designs with different geometry and dimensions were compared. It was found that sieve-based lateral displacement devices are able to displace particles due to the crucial role of the flow profile, despite of their unusual and asymmetric design. These results demonstrate the possibility to actively steer the velocity profile in order to reduce the critical diameter in deterministic lateral displacement devices, which makes this separation principle more accessible for large-scale, high throughput applications.
UPS-indel: a Universal Positioning System for Indels
Authors: Hasan Mohammad Shabbir , Wu Xiaowei , Watson Layne T. , Zhang Liqing
Published: October 2017

Storing biologically equivalent indels as distinct entries in databases causes data redundancy, and misleads downstream analysis. It is thus desirable to have a unified system for identifying and representing equivalent indels. Moreover, a unified system is also desirable to compare the indel calling results produced by different tools. This paper describes UPS-indel, a utility tool that creates a universal positioning system for indels so that equivalent indels can be uniquely determined by their coordinates in the new system, which also can be used to compare different indel calling results. UPS-indel identifies 15% redundant indels in dbSNP, 29% in COSMIC coding, and 13% in COSMIC noncoding datasets across all human chromosomes, higher than previously reported. Comparing the performance of UPS-indel with existing variant normalization tools vt normalize, BCFtools, and GATK LeftAlignAndTrimVariants shows that UPS-indel is able to identify 456,352 more redundant indels in dbSNP; 2,118 more in COSMIC coding, and 553 more in COSMIC noncoding indel dataset in addition to the ones reported jointly by these tools. Moreover, comparing UPS-indel to state-of-the-art approaches for indel call set comparison demonstrates its clear superiority in finding common indels among call sets. UPS-indel is theoretically proven to find all equivalent indels, and thus exhaustive.
Combining 18F-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma
Authors: Kornberg Arno , Witt Ulrike , Schernhammer Martina , Kornberg Jennifer , Ceyhan Gueralp O. , Mueller Katharina , Friess Helmut , Thrum Katharina
Published: October 2017

The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%; p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non- 18F-FDG-avid and 18F-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25; p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT.