bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calibration of concomitant field offsets using phase contrast MRI for asymmetric gradient coils
Authors: Abad Nastaren , Lee Seung‐Kyun , Ajala Afis , In Myung‐Ho , Frigo Louis M. , Bhushan Chitresh , Morris H. Douglas , Hua Yihe , Ho Vincent B. , Bernstein Matt A. , Foo Thomas K. F. 
Published: September 2022

PurposeAsymmetric gradient coils introduce zeroth‐ and first‐order concomitant field terms, in addition to higher‐order terms common to both asymmetric and symmetric gradients. Salient to compensation strategies is the accurate calibration of the concomitant field spatial offset parameters for asymmetric coils. A method that allows for one‐time calibration of the offset parameters is described.Theory and MethodsA modified phase contrast pulse sequence with single‐sided bipolar flow encoding is proposed to calibrate the offsets for asymmetric, transverse gradient coils. By fitting the measured phase offsets to different gradient amplitudes, the spatial offsets were calculated by fitting the phase variation. This was used for calibrating real‐time pre‐emphasis compensation of the zeroth‐ and first‐order concomitant fields.ResultsImage quality improvement with the proposed corrections was demonstrated in phantom and healthy volunteers with non‐Cartesian and Cartesian trajectory acquisitions. Concomitant field compensation using the calibrated offsets resulted in a residual phase error <3% at the highest gradient amplitude and demonstrated substantial reduction of image blur and slice position/selection artifacts.ConclusionsThe proposed implementation provides an accurate method for calibrating spatial offsets that can be used for real‐time concomitant field compensation of zeroth and first‐order terms, substantially reducing artifacts without retrospective correction or sequence specific waveform modifications.
Got funds? Best practices for successful grant applications
Authors: Sutton Halley 
Published: September 2022

LAS VEGAS — “I spent about 16 years at Syracuse University, in their emergency communications department. In [this] my former job, ‘no’ was never an option. I had to find a solution [to whatever problem we faced]. Grant funding is similar,” Shannon Day, Grants Development Consultant, Grants Office, LLC, said.
Graphene oxide/epoxy composites with enhanced fracture toughness for liquid hydrogen storage
Authors: Chen Qiang , Sun Tao , Fan Hongyu , Yan Jia , Wu Zhanjun 
Published: September 2022

AbstractGraphene oxide (GO)/epoxy composites cured by aliphatic dibasic acids have been prepared. The influences of structure of aliphatic dibasic acid and loading of GO on curing process and mechanical properties of epoxy composites were studied. The results show that the reaction activities, gel time of corresponding epoxy‐acid system and tensile strength of the formed epoxy resins decrease with the increase of the chain length of aliphatic dibasic acids. Both fracture toughness (>1.96 MPa⋅m1/2) and elongations at break (>6%) increase with the increase of the chain length of aliphatic dibasic acids. The introduction of GO is helpful to increase the mechanical properties and the gas transmission coefficient of GO/epoxy composites. A maximum of tensile strength and elongations at break were obtained when the loading of GO is 0.6 wt%. The gas transmission coefficient of GO/epoxy composite increases with the increase of GO loading. The excellent mechanical properties and gas leakage resistance coefficient of the formed epoxy composites provides potential application in many fields where conventional brittle epoxy resins are inapplicable.
Percutaneous ablation of malignant and locally aggressive solid tumors in pediatric patients
Authors: Hawari Mohamad El , Moussa Amgad , Erinjeri Joseph P. , Ziv Etay , Maybody Majid , Santos Martin Ernesto G. , Solomon Stephen B. , Gonzalez‐Aguirre Adrian J. 
Published: September 2022

AbstractImage‐guided percutaneous ablation is an accepted treatment modality for common adult cancers. Unfortunately, its use in patients younger than 18 years is rare. This retrospective review presents our series of pediatric patients treated with ablation at our institution. From January 2002 to December 2021, a total of 14 patients (17 lesions) younger than 18 years were treated with percutaneous image‐guided ablation. Estimated overall survival at 5 years was 58%; median survival of this group was not reached. Estimated local tumor progression‐free survival at 5 years was 62%. One major complication was recorded.
Social rather than physical crowding reduces the required interpersonal distance in virtual environments
Authors: Han Ming , Wang Xue‐Min , Kuai Shu‐Guang 
Published: September 2022

AbstractInterpersonal distance plays an important role in human social interaction. With the increasing usage of virtual reality in social interaction, people's interpersonal distance in virtual space attracts great attention. It remains unclear whether and to what extent human‐required interpersonal distance is altered by crowded virtual scenes. In this study, we manipulated crowd density in virtual environments and used the classical stop‐distance paradigm to measure required interpersonal distances at different crowd densities. We found that people's required interpersonal distance decreased with increased social crowdedness but not with physical crowdedness. Moreover, the decrease of two types of interpersonal distance was associated with the globally averaged crowd density rather than local crowd density. The reduction is not due to the imitation of other virtual humans in the crowd. Moreover, we developed a model to describe the quantitative relationships between the crowdedness of the environment and the required interpersonal distance. Our finding provides insights into designing user‐friendly virtual humans in metaverse virtual worlds.
Modified hypoxic challenge testing in children needing nocturnal ventilation: An observational study
Authors: Riley Mollie , Brotherston Stephanie , Kelly Paula , Samuels Martin , Pike Katharine C. 
Published: September 2022

AbstractBackgroundGuidelines for air passengers with respiratory disease focus on primary lung pathology. Little evidence exists to guide professionals advising children needing ventilatory support because of neuromuscular or central hypoventilation conditions; these children might risk hypoxia and hypercapnia if unable to mount an adequate hyperventilation response.ObjectiveThis study assessed the response to low ambient oxygen using a modified hypoxic challenge test. In addition to measuring pulse oximetry and response to supplementary oxygen, we also measured transcutaneous carbon dioxide and response to ventilatory support.MethodsTwenty children on nocturnal ventilatory support aged 1.6−18 years were recruited in a pragmatic sample from outpatient clinics; 10 with neuromuscular weakness and 10 with central hypoventilation. Participants underwent a two‐stage, modified hypoxic challenge test; a conventional stage, where oxygen alone was titrated according to SpO2, and a new stage, where participants used their routine ventilatory support with oxygen titrated if needed. Participants were interviewed to understand their experiences of testing and of air travel.ResultsThirteen participants needed supplemental oxygen during the conventional stage, but only two did when using ventilatory support. Transcutaneous carbon dioxide remained within normal range for all participants, on or off ventilatory support. Whilst some participants found testing challenging, participants generally reported both testing and air travel to be valuable.ConclusionsEvaluating response to patients' usual ventilation through “fitness‐to‐fly” assessment aids decision making when considering whether children who receive nocturnal ventilation can travel by air, since for some using a ventilator reduces or avoids the need for supplemental oxygen.
Longitudinal assessment of maternal depression and early childhood asthma and wheeze: Effect modification by child sex
Authors: Alcala Cecilia S. , Orozco Scott Paloma , Tamayo‐Ortiz Marcela , Hernández Chávez Maria del Carmen , Schnaas Lourdes , Carroll Kecia N. , Niedzwiecki Megan M. , Wright Robert O. , Téllez‐Rojo Martha Maria , Wright Rosalind J. , Hsu Hsiao‐Hsien Leon , Rosa Maria José 
Published: September 2022

AbstractBackgroundStudies report associations between maternal mental health and adverse respiratory outcomes in children; however, the impact of timing and duration of maternal distress remains understudied. We sought to longitudinally examine associations between maternal depression and childhood asthma and wheeze, and explore sex differences.MethodsMaternal depression (n = 601) was assessed using the Edinburgh Depression Scale questionnaire, dichotomized at a clinically relevant cutoff (>12) (a) during pregnancy, (b) postpartum, and (c) postpartum and subsequent time points postnatally (recurrent depression). Report of wheeze in the past 12 months (current wheeze) and asthma were obtained using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire at 48 and 72 months. Associations were analyzed using a modified Poisson regression adjusted for covariates, and in interaction models.ResultsBoth postpartum and recurrent depression were associated with higher risk of current wheeze (relative risk [RR]: 1.87, 95% confidence interval [CI]: 1.21, 2.90; RR: 2.41, 95% CI: 1.53, 3.79) and asthma at 48 months (RR: 2.42, 95% CI: 1.01, 5.84; RR: 2.45, 95% CI: 1.02, 5.84). In interaction analyses, associations were stronger in females. Recurrent depression was associated with a higher risk of current wheeze at 48 months in females (RR: 4.34, 95% CI: 2.02, 9.32) when compared to males (RR: 1.89, 95% CI: 1.05, 3.39).ConclusionsPostpartum and recurrent depression were associated with a higher risk of wheeze and asthma in children. Understanding the temporal‐ and sex‐specific effects of maternal depression may better inform prevention strategies.
Saturation mutagenesis of a predicted ancestral Syk‐family kinase
Authors: Hobbs Helen T. , Shah Neel H. , Shoemaker Sophie R. , Amacher Jeanine F. , Marqusee Susan , Kuriyan John 
Published: September 2022

AbstractMany tyrosine kinases cannot be expressed readily in Escherichia coli, limiting facile production of these proteins for biochemical experiments. We used ancestral sequence reconstruction to generate a spleen tyrosine kinase (Syk) variant that can be expressed in bacteria and purified in soluble form, unlike the human members of this family (Syk and zeta‐chain‐associated protein kinase of 70 kDa [ZAP‐70]). The catalytic activity, substrate specificity, and regulation by phosphorylation of this Syk variant are similar to the corresponding properties of human Syk and ZAP‐70. Taking advantage of the ability to express this novel Syk‐family kinase in bacteria, we developed a two‐hybrid assay that couples the growth of E. coli in the presence of an antibiotic to successful phosphorylation of a bait peptide by the kinase. Using this assay, we screened a site‐saturation mutagenesis library of the kinase domain of this reconstructed Syk‐family kinase. Sites of loss‐of‐function mutations identified in the screen correlate well with residues established previously as critical to function and/or structure in protein kinases. We also identified activating mutations in the regulatory hydrophobic spine and activation loop, which are within key motifs involved in kinase regulation. Strikingly, one mutation in an ancestral Syk‐family variant increases the soluble expression of the protein by 75‐fold. Thus, through ancestral sequence reconstruction followed by deep mutational scanning, we have generated Syk‐family kinase variants that can be expressed in bacteria with very high yield.
Probing the effect of NEK7 and cofactor interactions on dynamics of NLRP3 monomer using molecular simulation
Authors: El‐Sayed Sherihan , Freeman Sally , Bryce Richard A. 
Published: September 2022

AbstractThe NLRP3 inflammasome is a cytoplasmic complex that regulates the activation of inflammatory cytokines and, given its implication in a range of diseases, is an important therapeutic target. The cofactor ATP and the centrosomal kinase NEK7 are important for NLRP3 activation. Here we have constructed and simulated computational models of full‐length monomeric NLRP3 to shed light on the importance of NEK7 and cofactor interactions for its conformation and dynamics in aqueous solution. We find that molecular dynamics simulation reproduces well the features of the recently published cryo‐EM structure of the ADP‐bound NLRP3–NEK7 complex; on the removal of NEK7, the NLRP3 molecule adopts a more compact closed form during simulations. Replacement of ADP by ATP promotes a rearrangement of hydrogen‐bonding interactions, domain interfaces, and a degree of opening of the NLRP3 conformation. We also examine the dynamics of an acidic loop of the LRR domain of NLRP3, which samples in a region observed in the NEK7‐bound cryo‐EM structure but not in an oligomeric form of inactive NLRP3. During the molecular dynamics simulations of NLRP3, we find some plasticity in its topology that suggests access routes for ATP to the cofactor pocket not immediately evident from the existing NEK7‐bound cryo‐EM structure. These computed dynamical trajectories of NLRP3 provide insight into coordinates of deformation that may be key for cofactor binding and inflammasome activation.
Predicted structure of the hepatitis B virus polymerase reveals an ancient conserved protein fold
Authors: Tajwar Razia , Bradley Daniel P. , Ponzar Nathan L. , Tavis John E. 
Published: September 2022

AbstractHepatitis B virus (HBV) chronically infects >250 million people. It replicates by a unique protein‐primed reverse transcription mechanism, and the primary anti‐HBV drugs are nucleos(t)ide analogs targeting the viral polymerase (P). P has four domains compared to only two in most reverse transcriptases: the terminal protein (TP) that primes DNA synthesis, a spacer, the reverse transcriptase (RT), and the ribonuclease H (RNase H). Despite being a major drug target and catalyzing a reverse transcription pathway very different from the retroviruses, HBV P has resisted structural analysis for decades. Here, we exploited computational advances to model P. The TP wrapped around the RT domain rather than forming the anticipated globular domain, with the priming tyrosine poised over the RT active site. The orientation of the RT and RNase H domains resembled that of the retroviral enzymes despite the lack of sequences analogous to the retroviral linker region. The model was validated by mapping residues with known surface exposures, docking nucleic acids, mechanistically interpreting mutations with strong phenotypes, and docking inhibitors into the RT and RNase H active sites. The HBV P fold, including the orientation of the TP domain, was conserved among hepadnaviruses infecting rodent to fish hosts and a nackednavirus, but not in other non‐retroviral RTs. Therefore, this protein fold has persisted since the hepadnaviruses diverged from nackednaviruses >400 million years ago. This model will advance mechanistic analyses into the poorly understood enzymology of HBV reverse transcription and will enable drug development against non‐active site targets for the first time.
A methodology for creating mutants of G‐protein coupled receptors stabilized in active state by combining statistical thermodynamics and evolutionary molecular engineering
Authors: Yamamoto Taisei , Yasuda Satoshi , Kasai Rinshi S. , Nakano Ryosuke , Hikiri Simon , Sugaya Kanna , Hayashi Tomohiko , Ogasawara Satoshi , Shiroishi Mitsunori , Fujiwara Takahiro K. , Kinoshita Masahiro , Murata Takeshi 
Published: September 2022

AbstractWe challenged the stabilization of a G‐protein coupled receptor (GPCR) in the active state solely by multiple amino‐acid mutations without the agonist binding. For many GPCRs, the free energy of the active state is higher than that of the inactive state. When the inactive state is stabilized through the lowering of its free energy, the apparent midpoint temperature of thermal denaturation Tm exhibits a significant increase. However, this is not always the case for the stabilization of the active state. We constructed a modified version of our methodology combining statistical thermodynamics and evolutionary molecular engineering, which was recently developed for the inactive state. First, several residues to be mutated are determined using our statistical‐thermodynamics theory. Second, a gene (mutant) library is constructed using Escherichia coli cells to efficiently explore most of the mutational space. Third, for the mutant screening, the mutants prepared in accordance with the library are expressed in engineered Saccharomyces cerevisiae YB14 cells which can grow only when a GPCR mutant stabilized in the active state has signaling function. For the adenosine A2A receptor tested, the methodology enabled us to sort out two triple mutants and a double mutant. It was experimentally corroborated that all the mutants exhibit much higher binding affinity for G protein than the wild type. Analyses indicated that the mutations make the structural characteristics shift toward those of the active state. However, only slight increases in Tm resulted from the mutations, suggesting the unsuitability of Tm to the stability measure for the active state.
Multiple pore lining residues modulate water permeability of GlpF
Authors: Pluhackova Kristyna , Schittny Valentin , Bürkner Paul‐Christian , Siligan Christine , Horner Andreas 
Published: September 2022

AbstractThe water permeability of aquaporins (AQPs) varies by more than an order of magnitude even though the pore structure, geometry, as well as the channel lining residues are highly conserved. However, channel gating by pH, divalent ions or phosphorylation was only shown for a minority of AQPs. Structural and in silico indications of water flux modulation by flexible side chains of channel lining residues have not been experimentally confirmed yet. Hence, the aquaporin “open state” is still considered to be a continuously open pore with water molecules permeating in a single‐file fashion. Using protein mutations outside the selectivity filter in the aqua(glycerol)facilitator GlpF of Escherichia coli we, to the best of our knowledge, for the first time, modulate the position of the highly conserved Arg in the selectivity filter. This in turn enhances or reduces the unitary water permeability of GlpF as shown in silico by molecular dynamics (MD) simulations and in vitro with purified and reconstituted GlpF. This finding suggests that AQP water permeability can indeed be regulated by lipid bilayer asymmetry and the transmembrane potential. Strikingly, our long‐term MD simulations reveal that not only the conserved Arg in the selectivity filter, but the position and dynamics of multiple other pore lining residues modulate water passage through GlpF. This finding is expected to trigger a wealth of future investigations on permeability and regulation of AQPs among others with the aim to tune water permeability for biotechnological applications.
Mapping the interaction between Trim28 and the KRAB domain at the center of Trim28 silencing of endogenous retroviruses
Authors: Taka Jamie R. H. , Sun Yunyuan , Goldstone David C. 
Published: September 2022

AbstractTranscription of endogenous retroviral elements are tightly regulated during development by members of the KRAB‐containing zinc finger proteins (KRAB‐ZFPs) and the co‐repressor Trim28 (also known as Kap‐1 or Tif1β). KRAB‐ZFPs form the largest family of transcription regulators in mammals and initiate transcriptional silencing by tethering Trim28 to a target locus. Subsequently, Trim28 recruits chromatin modifying effectors resulting in the formation of heterochromatin. In the present study, we identify surface exposed residues on the central six turns of the Trim28 coiled‐coil region forming the binding interface for the KRAB domain. Using AlphaFold2 (AF2) we provide high confidence models of the interface between Trim28 and the KRAB domain and identified leucine 301 on each chain of the Trim28 monomer to act as a pin extending into a hydrophobic pocket on the KRAB domain surface. Site directed mutations in the Trim28‐KRAB binding interface abolished binding to the KRAB domain. Our work provides a detailed understanding of the specific interactions between the KRAB domain and the Trim28 coiled‐coil and how this interaction may be regulated during silencing events.
Acute urinary retention in men: 21‐year trends in incidence, subsequent benign prostatic hyperplasia‐related treatment and mortality: A Danish population‐based cohort study
Authors: Bengtsen Maria Bisgaard , Heide‐Jørgensen Uffe , Borre Michael , Knudsen Jakob S. , Nørgaard Mette 
Published: September 2022

AbstractObjectiveTo examine trends in incidence of acute urinary retention, subsequent benign prostatic hyperplasia‐related treatment and mortality in the era of medical therapy for benign prostatic hyperplasia. Additionally, to compare mortality with the general population.Materials and MethodsWe conducted a Danish nationwide registry‐based study including 70,775 men aged 45 years or older with a first hospitalization for acute urinary retention during 1997–2017. We computed annual standardized incidence rates, subsequent 1‐year cumulative incidence of benign prostatic hyperplasia‐related surgical and medical treatment, and standardized 3‐month and 1‐year mortality rates. Finally, we compared standardized all‐cause and cause‐specific mortality ratios with the general population.ResultsThe standardized incidence rate of acute urinary retention per 1000 person‐years increased transiently from 2.34 to 3.42 during 1997–2004, but gradually declined to 2.95 in 2017.The 1‐year cumulative incidence of benign prostatic hyperplasia‐related surgery declined from 31.2% to 19.8% and 20.5% to 7.7% after spontaneous and precipitated acute urinary retention, respectively. During 1997–2017, the standardized 1‐year mortality declined from 22.2% to 17.2%. Compared with the general population, mortality was 4–5 times higher after 3 months and 2–3 times higher after 1 year of acute urinary retention. The cause‐specific standardized mortality ratios were particularly high for deaths attributable to malignancies, urogenital disease, certain infections, chronic pulmonary disease, and diabetes.ConclusionDuring 1997–2017, we observed a transient increase in the incidence of acute urinary retention. The subsequent use of benign prostatic hyperplasia‐related surgery declined considerably and mortality continued to be high, mainly because of deaths from malignancies, urogenital disease, infections, and preexisting comorbidity.