bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental studies of a high-gradient X-band welded hard-copper split accelerating structure
Authors: Agustsson R , Carriere P , Chimalpopoca O , Dolgashev V А , Gusarova M A , Kutsaev S V , Smirnov A Yu
Published: December 2021

Recent research on high-gradient radio frequency (RF) accelerating structures indicates that the use of hard copper alloys provides improvement in high gradient performance over annealed copper. Such structures are made by bonding individually manufactured parts. However, there are no well-established bonding techniques that preserve the hardness, surface finish and cleanliness required for high gradient operation. To preserve the copper hardness, RadiaBeam has developed a novel high-gradient split accelerating structure, based on electron beam welding joining technique. This technique provides efficient bonding with strong, clean welds and minimal thermal loading, while maintaining a clean inner RF environment. Our RF design and fabrication methodology limits the small heat affected zone to the outer cavity envelop, with virtually no distortions or thermal loading of critical RF surfaces. It also incorporates provisions to precisely control the gap despite conventional issues with weld joint shrinkage. To date we have manufactured and validated an RF accelerating structure joined by electron-beam welding that incorporates a novel open split design to significantly reduce the assembly complexity and cost. In this paper, we will present the electromagnetic design of this structure, discuss bonding, and present the results of high-power tests, where the accelerating gradients of 140 MV m−1 with surface peak fields of 400 MV m−1 were achieved for flat-top pulse length of 600 ns with an RF breakdown rate of 10−4 1/(pulseċm).
Self-assembly of hydrophobic–amphiphilic diblock copolymers in solution
Authors: Pavlenko Sophia A , Larin Daniil E , Govorun Elena N
Published: December 2021

Thermoresponsive polymers are usually characterized by a locally amphiphilic chain structure and their self-assembly in solution is controlled, in particular, by the surface activity of the monomer units or side chains. We theoretically study the condensed state of a single diblock copolymer molecule consisting of a hydrophobic block and amphiphilic block with hydrophobic groups in the backbone and pendant polar groups. The equilibrium parameters of the polymer globules of different shapes are determined using the mean-field approach to determine the most favorable structure. Morphological diagrams of condensed macromolecules are presented depending on the chain length, amphiphilic block fraction, interaction parameters, and pendant volume and length. The diagrams are compared with those of a copolymer molecule with the same fraction of amphiphilic monomer units which are regularly distributed along the chain. The diblock copolymer molecule is found to form a single spherical or flattened particle, with the core from the hydrophobic block, or a granular micelle consisting of spherical or nearly spherical particles, in agreement with the experimental data in the literature. The optimal chain parameters for self-assembly into a stable single core–shell particle are predicted.
What happens next? Ink markers
Authors: Featonby David , Dovalová Kristína
Published: December 2021

Coloured marker pens come with different properties according to their uses. This question relates to how these properties are affected by water.
Unleashing the full power of LHCb to probe stealth new physics
Authors: Borsato M , Cid Vidal X , Tsai Y , Vázquez Sierra C , Zurita J , Alonso-Álvarez G , Boyarsky A , Brea Rodríguez A , Buarque Franzosi D , Cacciapaglia G , Casais Vidal A , Du M , Elor G , Escudero M , Ferretti G , Flacke T , Foldenauer P , Hajer J , Henry L , Ilten P , Kamenik J , Kishor Jashal B , Knapen S , Kostiuk Igor , Redi F L , Low M , Liu Z , Oyanguren Campos A , Polycarpo E , Ramos M , Ramos Pernas M , Salvioni E , Rangel M S , Schäfer R , Sestini L , Soreq Y , Tran V Q , Timiryasov I , van Veghel M , Westhoff S , Williams M , Zupan J
Published: December 2021

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.
Effects of annealing temperature on a ZnO thin film-based ultraviolet photodetector
Authors: Doğan Ümit , Sarcan Fahrettin , Koç Kamuran Kara , Kuruoğlu Furkan , Erol Ayşe
Published: December 2021

In this paper, the effects of annealing temperature on the performance of a ZnO thin film-based Metal-Semiconductor-Metal (MSM) type ultraviolet (UV) photodetector is reported. ZnO thin films were grown on a glass substrate using the Pulsed Filtered Cathodic Vacuum Arc Deposition (PFCVAD) technique at room temperature and after the deposition process the samples were annealed at 400, 450 and 550 °C in air condition to investigate the annealing effect on the structural, electrical, and optical properties of the photodetector. ZnO thin films which have grains in nanometer range has an increasing in the diameter of grains from 10.5 to 18.3 nm as a function of annealing temperature results in a red shift in the cut-off wavelength of the photodetector from 3.25 eV (381 nm) to 3.23 eV (383 nm). It is demonstrated that the sensitivity and the speed (rise/fall times) of the ZnO thin film based MSM photodetectors enhances with increasing post growth annealing temperature of ZnO thin film due to the increase in the absorption coefficient and the decrease of the total area of the grain boundaries due to the larger grain sizes formation in ZnO thin films with increasing thermal annealing temperature.
Comparison of dynamical features between the fast H-L and the H-I-L transition for EAST RF-heated plasmas
Authors: Chen Liang , Xu Guosheng , Shao Lingming , Gao Wei , Wang Yifeng , Duan Yanmin , Wang Shouxin , Ti Ang , Mao Songtao , Li Miaohui , Zhang Xinjun , Chen Ran , Hu Guanghai , Liu Jianbin , Xu Jichan , Yan Ning , Wu Xingquan , Nielsen Anders Henry , Rasmussen Jens Juul , Wang Liang , Gong Xianzu
Published: December 2021

In this paper, a comparison of dynamical features between the fast H-L and the H-I-L transition, which can be identified by the intermediate phase, or ‘I-phase’, has been made for radio-frequency (RF) heated deuterium plasmas in EAST. The fast H-L transition is characterized by a rapid release of stored energy during the transition transient, while the H-I-L transition exhibits a ‘soft’ H-mode termination. One important distinction between the transitions has been observed by dedicated probe measurements slightly inside the separatrix, with respect to the radial gradient of the floating potential, which corresponds to the E × B flow and/or the electron temperature gradient. The potential gradient inside the separatrix oscillates and persists during the stationary I-phase, and shows a larger amplitude than that before the fast H-L transition. The reduction of the gradient leads to the final transition to the L-mode for both the fast H-L and the H-I-L transition. These findings indicate that the mean E × B flow shear and/or edge electron temperature gradient play a critical role underlying the H-L transition physics. In addition, the back transition in EAST is found to be sensitive to magnetic configuration, where the vertical configuration, i.e., inner strike-point located at vertical target, favours access to the H-I-L transition, while the horizontal shape facilitates achievement of the fast H-L transition. The divertor recycling level normalized to electron density is higher before the fast H-L transition, as compared to that before the I-phase, which strongly suggest that the density of the recycled neutrals is an important ingredient in determining the back transition behaviour.
Confirmation and variability of the Allee effect in Dictyostelium discoideum cell populations, possible role of chemical signaling within cell clusters
Authors: Segota Igor , Edwards Matthew M , Campello Arthur , Rappazzo Brendan H , Wang Xiaoning , Strandburg-Peshkin Ariana , Zhou Xiao-Qiao , Rachakonda Archana , Daie Kayvon , Lussenhop Alexander , Lee Sungsu , Tharratt Kevin , Deshmukh Amrish , Sebesta Elisabeth M , Zhang Myron , Lau Sharon , Bennedsen Sarah , Ginsberg Jared , Campbell Timothy , Wang Chenzheng , Franck Carl
Published: December 2021

In studies of the unicellular eukaryote Dictyostelium discoideum, many have anecdotally observed that cell dilution below a certain ‘threshold density’ causes cells to undergo a period of slow growth (lag). However, little is documented about the slow growth phase and the reason for different growth dynamics below and above this threshold density. In this paper, we extend and correct our earlier work to report an extensive set of experiments, including the use of new cell counting technology, that set this slow-to-fast growth transition on a much firmer biological basis. We show that dilution below a certain density (around 104 cells ml−1) causes cells to grow slower on average and exhibit a large degree of variability: sometimes a sample does not lag at all, while sometimes it takes many moderate density cell cycle times to recover back to fast growth. We perform conditioned media experiments to demonstrate that a chemical signal mediates this endogenous phenomenon. Finally, we argue that while simple models involving fluid transport of signal molecules or cluster-based signaling explain typical behavior, they do not capture the high degree of variability between samples but nevertheless favor an intra-cluster mechanism.
Gradient biomimetic platforms for neurogenesis studies
Authors: Havins Laurissa , Capel Andrew , Christie Steve , Lewis Mark , Roach P
Published: December 2021

There is a need for the development of new cellular therapies for the treatment of many diseases, with the central nervous system (CNS) currently an area of specific focus. Due to the complexity and delicacy of its biology, there is currently a limited understanding of neurogenesis and consequently a lack of reliable test platforms, resulting in several CNS based diseases having no cure. The ability to differentiate pluripotent stem cells into specific neuronal sub-types may enable scalable manufacture for clinical therapies, with a focus also on the purity and quality of the cell population. This focus is targeted towards an urgent need for the diseases that currently have no cure, e.g. Parkinson’s disease. Differentiation studies carried out using traditional 2D cell culture techniques are designed using biological signals and morphogens known to be important for neurogenesis in vivo. However, such studies are limited by their simplistic nature, including a general poor efficiency and reproducibility, high reagent costs and an inability to scale-up the process to a manufacture-wide design for clinical use. Biomimetic approaches to recapitulate a more in vivo-like environment are progressing rapidly within this field, with application of bio(chemical) gradients presented both as 2D surfaces and within a 3D volume. This review focusses on the development and application of these advanced extracellular environments particularly for the neural niche. We emphasise the progress that has been made specifically in the area of stem cell derived neuronal differentiation. Increasing developments in biomaterial approaches to manufacture stem cells will enable the improvement of differentiation protocols, enhancing the efficiency and repeatability of the process with a move towards up-scaling. Progress in this area brings these techniques closer to enabling the development of therapies for the clinic.
Single-stage gradient-based stellarator coil design: stochastic optimization
Authors: Wechsung Florian , Giuliani Andrew , Landreman Matt , Cerfon Antoine , Stadler Georg
Published: December 2021

We extend the single-stage stellarator coil design approach for quasi-symmetry on axis from (Giuliani et al 2020) to additionally take into account coil manufacturing errors. By modeling coil errors independently from the coil discretization, we have the flexibility to consider realistic forms of coil errors. The corresponding stochastic optimization problems are formulated using a risk-neutral approach and risk-averse approaches. We present an efficient, gradient-based descent algorithm which relies on analytical derivatives to solve these problems. In a comprehensive numerical study, we compare the coil designs resulting from deterministic and risk-neutral stochastic optimization and find that the risk-neutral formulation results in more robust configurations and reduces the number of local minima of the optimization problem. We also compare deterministic and risk-neutral approaches in terms of quasi-symmetry on and away from the magnetic axis, and in terms of the confinement of particles released close to the axis. Finally, we show that for the optimization problems we consider, a risk-averse objective using the conditional value-at-risk leads to results which are similar to the risk-neutral objective.
Discontinuous yielding transition of amorphous materials with low bulk modulus
Authors: Jagla E A
Published: December 2021

The yielding transition of amorphous materials is studied with a two-dimensional Hamiltonian model that allows both shear and volume deformations. The model is investigated as a function of the relative value of the bulk modulus B with respect to the shear modulus μ. When the ratio B/μ is small enough, the yielding transition becomes discontinuous, yet reversible. If the system is driven at constant strain rate in the coexistence region, a spatially localized shear band is observed while the rest of the system remains blocked. The crucial role of volume fluctuations in the origin of this behavior is clarified in a mean field version of the model.
A new measure between sets of probability distributions with applications to erratic financial behavior
Authors: James Nick , Menzies Max
Published: December 2021

This paper introduces a new framework to quantify distance between finite sets with uncertainty present, where probability distributions determine the locations of individual elements. Combining this with a Bayesian change point detection algorithm, we produce a new measure of similarity between time series with respect to their structural breaks. First, we demonstrate the algorithm’s effectiveness on a collection of piecewise autoregressive processes. Next, we apply this to financial data to study the erratic behavior profiles of 19 countries and 11 sectors over the past 20 years. Our measure provides quantitative evidence that there is greater collective similarity among sectors’ erratic behavior profiles than those of countries, which we observe upon individual inspection of these time series. Our measure could be used as a new framework or complementary tool for investors seeking to make asset allocation decisions for financial portfolios.
How to avoid the faster-is-slower effect in competitive evacuation?
Authors: Qiu Hongpeng , Yang Xinyu , Chen Xingchao , Xiong Yuanyuan , Ma Jian , Lin Peng
Published: December 2021

The faster-is-slower (FIS) effect is an interesting phenomenon in crowd dynamics. However, the validity of FIS was not universally accepted without objection. A series of experiments was conducted by using a group of young students in a room evacuating through a narrow exit at two locations, i.e. a center exit and a corner exit. The mean time intervals of two consecutive persons passing through a center exit were 1.14 ± 0.09, 1.31 ± 0.43 and 1.42 ± 0.93 s at low, medium and high competitiveness, respectively, i.e. which was the FIS effect. However, the mean time intervals of two consecutive persons passing through a corner exit were 1.04 ± 0.07 and 0.85 ± 0.17 s at low and high competitiveness, respectively, which was contrary to the FIS effect. Furthermore, two series of circulation movement at high competiveness were studied in which all students were required to re-enter the room from another opening after getting out of the room and this process continued until the end of a test. The mean time interval of consecutive persons passing through the exits was around 2.39 ± 4.29 and 0.77 ± 0.25 s for the center exit and corner exit respectively, and the flow rate of the corner exit was around 3 times that of the center exit. The complementary cumulative probability distribution of the time intervals between consecutive students Δt was studied and it followed a power law, i.e.

P

Δ
t

∼
Δ

t

−
a
l
p
h
a

. However, the study showed that alpha alone cannot well represent the efficiency of an evacuation. The experiment demonstrated that the FIS effect can be avoided by relocating the exit to the corner and the flow rate can be greatly improved, particularly in high competiveness conditions.
Survival probability of random walks leaping over traps
Authors: Pozzoli Gaia , De Bruyne Benjamin
Published: December 2021

We consider one-dimensional discrete-time random walks (RWs) in the presence of finite size traps of length ℓ over which the RWs can jump. We study the survival probability of such RWs when the traps are periodically distributed and separated by a distance L. We obtain exact results for the mean first-passage time and the survival probability in the special case of a double-sided exponential jump distribution. While such RWs typically survive longer than if they could not leap over traps, their survival probability still decreases exponentially with the number of steps. The decay rate of the survival probability depends in a non-trivial way on the trap length ℓ and exhibits an interesting regime when ℓ → 0 as it tends to the ratio ℓ/L, which is reminiscent of strongly chaotic deterministic systems. We generalize our model to continuous-time RWs, where we introduce a power-law distributed waiting time before each jump. In this case, we find that the survival probability decays algebraically with an exponent that is independent of the trap length. Finally, we derive the diffusive limit of our model and show that, depending on the chosen scaling, we obtain either diffusion with uniform absorption, or diffusion with periodically distributed point absorbers.
Inhomogeneous asymmetric exclusion processes between two reservoirs: large deviations for the local empirical observables in the mean-field approximation
Authors: Monthus Cécile
Published: December 2021

For a given inhomogeneous exclusion processes on N sites between two reservoirs, the trajectories probabilities allow to identify the relevant local empirical observables and to obtain the corresponding rate function at level 2.5. In order to close the hierarchy of the empirical dynamics that appear in the stationarity constraints, we consider the simplest approximation, namely the mean-field approximation for the empirical density of two consecutive sites, in direct correspondence with the previously studied mean-field approximation for the steady state. For a given inhomogeneous totally asymmetric model, this mean-field approximation yields the large deviations for the joint distribution of the empirical density profile and of the empirical current around the mean-field steady state; the further explicit contraction over the current allows to obtain the large deviations of the empirical density profile alone. For a given inhomogeneous asymmetric model, the local empirical observables also involve the empirical activities of the links and of the reservoirs; the further explicit contraction over these activities yields the large deviations for the joint distribution of the empirical density profile and of the empirical current. The consequences for the large deviations properties of time-additive space-local observables are also discussed in both cases.
New module for channeling radiation simulation in Geant4
Authors: Savchenko A.A. , Wagner W.
Published: December 2021

We present a new C++ module for simulation of channeling
radiation to be implemented in Geant4 as a discrete physical
process. The module allows simulation of channeling radiation from
relativistic electrons and positrons with energies above 100 MeV
for various types of single crystals. In this paper, we simulate
planar channeling radiation applying the classical approach in the
dipole approximation as a first attempt not yet considering other
contributory processes. Simulation results are proved to be in a
rather good agreement with experimental data.
Forest governance and development effects on tropical charcoal production and deforestation
Authors: van 't Veen Hanneke , Vyamana Vincent G. , Santos Maria Joao
Published: December 2021

Severe loss and degradation of tropical forests affects ecosystem services and livelihoods. Charcoal, an important energy and income source for millions of people, causes 7% of tropical deforestation and forest degradation. Forest governance aims at managing forest-related issues. On the one hand, development allows for financial investments in forest governance, e.g., in monitoring and enforcement, which the aim to control deforestation. On the other hand, deforestation often continues with increased human wellbeing. Here, we aim to (i) globally examine effects of forest governance on charcoal production and deforestation, and (ii) understand its association with development. We developed a typology of tropical forest governance systems based on a literature review of 54 USAID Country Profiles and combined it with global data on charcoal production, deforestation, governance quality and development. Our results suggest that countries’ development status affects charcoal production rather than governance quality; we observe a negative relationship between development status and charcoal production per capita (HDI: F(1,50) = 4.85, p = 0.032; GNI: F(1,50) = 4.64, p = 0.036). The limited influence of governance quality and rights on charcoal production per capita and deforestation suggests mismatches between formal and informal governance and exposes challenges in top-down percolation of governance goals. Our results highlight potential importance of tenure rights and potential opportunities for regional governing bodies to bridge local formal and informal actors to improve forest governance. Positive effects of regional tenure are driven by mixed effects of high development and governance quality related to decentralization in Asia and South America, highlighting transitions from charcoal as livelihood energy source to global commodity. Variability in results for FAO and UN charcoal production data advocates for better monitoring programs. Yet, for the first time, we explore global interactive patterns in charcoal production, development and governance – a starting point to differentiate good governance.
Characterization of orientation correlation kinetics: chiral-mesophase domains in suspensions charged DNA-rods
Authors: Kang Kyongok
Published: December 2021

Bacteriophage DNA fd-rods are long and stiff rod-like particles which are known to exhibit a rich equilibrium phase behavior. Due to their helical molecular structure, they form the stable chiral nematic (N*) mesophases. Very little is known about the kinetics of forming various phases with orientations. The present study addresses the kinetics of chiral-mesophases and N*-phase, by using a novel image-time correlation technique. Instead of correlating time-lapsed real-space microscopy images, the corresponding Fourier images are shown for time-correlated averaged orientations. This allows to unambiguously distinguish to detect the temporal evolution of orientations on different length scales, such as domain sizes (depending on their relative orientations), and the chiral pitch within the domains. Kinetic features are qualitatively interpreted in terms of replica symmetry breaking of elastic deformations in the orthogonal directional axes of chiral-mesophase domains, as well by the average twist angle and the order parameter. This work can be interesting for characterizing other types of charged rods, mimicking super-cooled liquids and orientation glasses.
Decreasing drug waste, reducing drug costs, and improving workflow efficiency through the implementation of automated chemotherapy dose rounding rules in the electronic health record system
Authors: Shah Vishal , Spence Alexis , Bartels Trace , Betcher Jeffrey , Soefje Scott
Published: December 2021

Purpose

To decrease drug waste and cost by implementing automated chemotherapy dose rounding rules in the electronic health record (EHR). Dose rounding of chemotherapy is a recognized method for reducing drug waste, and professional organizations have published guidelines recommending dose rounding when possible.

On the basis of current literature and guideline recommendations, Mayo Clinic developed system-wide consensus to allow dose rounding for biologic and chemotherapy agents to the nearest vial size if rounding resulted in the dose being within 10% of the originally calculated dose or to a convenient measurable volume, based on concentration of the drug, if rounding to the nearest vial size resulted in the dose being outside the 10% range. Oncology pharmacists reviewed and analyzed all drugs listed in the EHR used in injectable form for the treatment of cancer and developed dose rounding rules. The rules were implemented and applied at the dose calculation stage before provider signature. From January to June 2019, approximately 40,000 cancer treatment doses were administered. The rounding rules saved a total of 9,814 vials of drug, of which 5,329 were for biologic agents and 4,485 were for oncolytic drugs. This resulted in a total 6-month cost savings of $7,284,796 (in 2019 dollars; biologics, $5,727,402; oncolytics, $1,557,394).

Conclusion

Systematic implementation of dose rounding rules utilizing the EHR can result in significant reduction of drug waste and realization of savings.
Prevalence of and incentives for board certification among hospital pharmacy departments in California
Authors: Yeung Samantha L , Vu Christina A , Wang Mengxi , Lou Mimi , Ng Tien M H
Published: December 2021

Purpose

Board of Pharmacy Specialties (BPS) certification is endorsed to distinguish pharmacists for advanced practice areas, yet perceived value to stakeholders remains poorly described. This study characterized how board certification is integrated in hospital pharmacy departments across California.

Methods

A prospective, cross-sectional study was conducted in which a survey was administered to all hospital pharmacy directors in California between November 2019 and March 2020. Licensed institutions and corresponding pharmacy directors were identified from the California State Board of Pharmacy. The survey queried for institution and pharmacy director characteristics and if/how board certification was integrated. Multivariable logistic models identified predictors of institutions with at least 25% full-time board certified pharmacists and those that reward board certification.

Results

Surveys were completed by 29% of institutions. Most of these institutions were urban (81%) and nonteaching (57%), with fewer than 325 hospital beds (71%), and with fewer than 50 full-time pharmacist positions (86%). The majority reported that less than 25% of their pharmacists were board certified. Currently, 47% consider board certification during hiring and 38% reward board certified employees. Predictors of institutions with 25% or more board certified pharmacists included being a teaching institution (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.24-7.06), having 325 or more beds (OR, 7.17; 95% CI, 2.86-17.97), and having a pharmacy director who was previously or currently board certified (OR, 3.69; 95% CI, 1.46-9.35). Hospitals with 100 or more pharmacist positions predicted institutions that reward board certification (OR, 16.69; 95% CI, 1.78-156.86).

Conclusion

Board certification was an employment preference for almost half of the hospital survey respondents in California. Institutions more likely to reward board certified pharmacists are larger, urban, and teaching hospitals and have pharmacy directors who have been board certified.
An inductive transfer learning force field (ITLFF) protocol builds protein force fields in seconds
Authors: Han Yanqiang , Wang Zhilong , Chen An , Ali Imran , Cai Junfei , Ye Simin , Li Jinjin
Published: December 2021

Accurate simulation of protein folding is a unique challenge in understanding the physical process of protein folding, with important implications for protein design and drug discovery. Molecular dynamics simulation strongly requires advanced force fields with high accuracy to achieve correct folding. However, the current force fields are inaccurate, inapplicable and inefficient. We propose a machine learning protocol, the inductive transfer learning force field (ITLFF), to construct protein force fields in seconds with any level of accuracy from a small dataset. This process is achieved by incorporating an inductive transfer learning algorithm into deep neural networks, which learn knowledge of any high-level calculations from a large dataset of low-level method. Here, we use a double-hybrid density functional theory (DFT) as a case functional, but ITLFF is suitable for any high-precision functional. The performance of the selected 18 proteins indicates that compared with the fragment-based double-hybrid DFT algorithm, the force field constructed by ITLFF achieves considerable accuracy with a mean absolute error of 0.0039 kcal/mol/atom for energy and a root mean square error of 2.57 $\mathrm{kcal}/\mathrm{mol}/{\AA}$ for force, and it is more than 30 000 times faster and obtains more significant efficiency benefits as the system increases. The outstanding performance of ITLFF provides promising prospects for accurate and efficient protein dynamic simulations and makes an important step toward protein folding simulation. Due to the ability of ITLFF to utilize the knowledge acquired in one task to solve related problems, it is also applicable for various problems in biology, chemistry and material science.
SARS-CoV-2 transmissibility compared between variants of concern and vaccination status
Authors: Wang Liang , Didelot Xavier , Bi Yuhai , Gao George F
Published: December 2021

Since the start of the SARS-CoV-2 pandemic in late 2019, several variants of concern (VOC) have been reported to have increased transmissibility. In addition, despite the progress of vaccination against SARS-CoV-2 worldwide, all vaccines currently in used are known to protect only partially from infection and onward transmission. We combined phylogenetic analysis with Bayesian inference under an epidemiological model to infer the reproduction number (Rt) and also trace person-to-person transmission. We examined the impact of phylogenetic uncertainty and sampling bias on the estimation. Our result indicated that lineage B had a significantly higher transmissibility than lineage A and contributed to the global pandemic to a large extent. In addition, although the transmissibility of VOCs is higher than other exponentially growing lineages, this difference is not very high. The probability of detecting onward transmission from patients infected with SARS-CoV-2 VOCs who had received at least one dose of vaccine was approximate 1.06% (3/284), which was slightly lower but not statistically significantly different from a probability of 1.21% (10/828) for unvaccinated individuals. In addition to VOCs, exponentially growing lineages in each country should also be account for when tailoring prevention and control strategies. One dose of vaccination could not efficiently prevent the onward transmission of SARS-CoV-2 VOCs. Consequently, nonpharmaceutical interventions (such as wearing masks and social distancing) should still be implemented in each country during the vaccination period.
GC-Profile 2.0: an extended web server for the prediction and visualization of CpG islands
Authors: Lai Fei-Liao , Gao Feng
Published: December 2021

Due to the spontaneous deamination of 5′-methylcytosine into thymine, the number of CpG dinucleotides is less than expected in vertebrate genomes. Exceptionally, there are a large number of CpG dinucleotides clustered at certain genomic loci, known as CpG islands (CGIs), where CpG dinucleotides are free from methylation. Identification of CGIs is of great significance in the field of genomics and epigenetics because they can serve as important gene markers or regulatory elements. Here, GC-Profile 2.0 has been presented as a newly extended application for CGIs detection and visualization. Based on a benchmark test of assembled sequences, GC-Profile 2.0 has shown better overall performance compared with other four popular methods. In addition, cumulative CpG profile, a visualization tool of CpG content variation, is also proposed to intuitively display the change trend of CpG content.

Availability and implementation

GC-Profile 2.0 is freely available at http://tubic.org/GC-Profile2.

Supplementary information

Supplementary data are available at Bioinformatics online.
HOMELETTE: a unified interface to homology modelling software
Authors: Junk Philipp , Kiel Christina
Published: December 2021

Homology modelling, the technique of generating models of 3D protein structures based on experimental structures from related proteins, has become increasingly popular over the years. An abundance of different tools for model generation and model evaluation is available from various research groups. We present HOMELETTE, an interface which implements a unified programmatic access to these tools. This allows for the assemble of custom pipelines from pre- or self-implemented building blocks.

Availability and implementation

HOMELETTE is implemented in Python, compatible with version 3.6 and newer. It is distributed under the MIT license. Documentation and tutorials are available at Read the Docs (https://homelette.readthedocs.io/). The latest version of HOMELETTE is available on PyPI (https://pypi.org/project/homelette/) and GitHub (https://github.com/PhilippJunk/homelette). A full installation of the latest version of HOMELETTE with all dependencies is also available as a Docker container (https://hub.docker.com/r/philippjunk/homelette_template).

Supplementary information

Supplementary data are available at Bioinformatics online.
Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice
Authors: Middleton Steven J , Perini Irene , Themistocleous Andreas C , Weir Greg A , McCann Kirsty , Barry Allison M , Marshall Andrew , Lee Michael , Mayo Leah M , Bohic Manon , Baskozos Georgios , Morrison India , Löken Line S , McIntyre Sarah , Nagi Saad S , Staud Roland , Sehlstedt Isac , Johnson Richard D , Wessberg Johan , Wood John N , Woods Christopher G , Moqrich Aziz , Olausson Håkan , Bennett David L
Published: December 2021

Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial electromyography (n = 3 CIP participants and n = 8 healthy controls), we found that these patients also have abnormalities in the encoding of affective touch, which is mediated by the specialized afferents C-low threshold mechanoreceptors (C-LTMRs).

In the mouse, we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient.

Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.
The oscillating Mucin-type protein DPY-6 has a conserved role in nematode mouth and cuticle formation
Authors: Sun Shuai , Theska Tobias , Witte Hanh , Ragsdale Erik J , Sommer Ralf J
Published: December 2021

Nematodes show an extraordinary diversity of mouth structures and strikingly different feeding strategies, which has enabled an invasion of all ecosystems. However, nearly nothing is known about the structural and molecular architecture of the nematode mouth (stoma). Pristionchus pacificus is an intensively studied nematode that exhibits unique life history traits, including predation, teeth-like denticle formation, and mouth-form plasticity. Here, we used a large-scale genetic screen to identify genes involved in mouth formation. We identified Ppa-dpy-6 to encode a Mucin-type hydrogel-forming protein that is macroscopically involved in the specification of the cheilostom, the anterior part of the mouth. We used a recently developed protocol for geometric morphometrics of miniature animals to characterize these defects further and found additional defects that affect mouth form, shape, and size resulting in an overall malformation of the mouth. Additionally, Ppa-dpy-6 is shorter than wild-type with a typical Dumpy phenotype, indicating a role in the formation of the external cuticle. This concomitant phenotype of the cheilostom and cuticle provides the first molecular support for the continuity of these structures and for the separation of the cheilostom from the rest of the stoma. In Caenorhabditis elegans, dpy-6 was an early mapping mutant but its molecular identity was only determined during genome-wide RNAi screens and not further investigated. Strikingly, geometric morphometric analysis revealed previously unrecognized cheilostom and gymnostom defects in Cel-dpy-6 mutants. Thus, the Mucin-type protein DPY-6 represents to the best of our knowledge, the first protein involved in nematode mouth formation with a conserved role in cuticle deposition. This study opens new research avenues to characterize the molecular composition of the nematode mouth, which is associated with extreme ecological diversification.
Bioethics and Gerontology: The Value of Thinking Together
Authors: Berlinger Nancy , de Medeiros Kate , Girling Laura
Published: December 2021

The interdisciplinary field of bioethics focuses on what it means to be a person, flourish as a person, and be respected as a person in different conditions of health, illness, or disability. Bioethics and policy research considers normative questions such as how a good society, through its priorities and investments, should demonstrate its commitments to the lives of different populations. Bioethics and humanities scholarship, often known as “health humanities,” shares affinities with age studies and disability studies and with narrative-based approaches to the study of human experience. Gerontology is concerned with the many aspects of life that affect how people age, including social structures and values that influence the experience of growing old. In this article, we briefly explore the evolution of bioethics, from a discourse that emerged in relation to developments in biomedicine, bioscience, and biotechnology; to research ethics; to broader ethical questions emerging from real-world conditions, with attention to how bioethics has considered the experience of aging. Until recently, most age-focused work in bioethics has concerned age-associated illness, particularly end-of-life decision making. Given the reality of population aging and the ethical concerns accompanying the shift in age for most places in the world, the further evolution of bioethics involves greater attention to the support of flourishing in late life and to social justice and health equity in aging societies. We argue that the discourses of bioethics and critical gerontology, in dialogue, can bring a new understanding of privilege and preference, disparity and disadvantage, and reflection and respect for aging individuals.
Voice Hearing in Borderline Personality Disorder Across Perceptual, Subjective, and Neural Dimensions
Authors: Strawson Will H , Wang Hao-Ting , Quadt Lisa , Sherman Maxine , Larsson Dennis E O , Davies Geoff , Mckeown Brontë L A , Silva Marta , Fielding-Smith Sarah , Jones Anna-Marie , Hayward Mark , Smallwood Jonathan , Critchley Hugo D , Garfinkel Sarah N
Published: December 2021

Background

Auditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as “pseudohallucinations,” but they nevertheless have a detrimental impact on well-being.

Methods

The current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively.

Results

Perceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level–dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices.

Conclusion

In summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as “pseudohallucinations.” These highlight a need to reconsider this experience as a treatment priority.
On the Convergence Rate of the Chaos Game
Authors: Bárány Balázs , Jurga Natalia , Kolossváry István
Published: December 2021

This paper studies how long it takes the orbit of the chaos game to reach a certain density inside the attractor of a strictly contracting IFS of which we only assume that its lower dimension is positive. We show that the rate of growth of this cover time is determined by the Minkowski dimension of the push-forward of the shift invariant measure with exponential decay of correlations driving the chaos game. Moreover, we bound the expected value of the cover time from above and below with multiplicative logarithmic correction terms. As an application, for Bedford–McMullen carpets, we completely characterise the family of probability vectors that minimise the Minkowski dimension of Bernoulli measures. Interestingly, these vectors have not appeared in any other aspect of Bedford–McMullen carpets before.
Existence and Stability of Smooth Traveling Circular Pairs for the Generalized Surface Quasi-Geostrophic Equation
Authors: Cao Daomin , Qin Guolin , Zhan Weicheng , Zou Changjun
Published: December 2021

In this paper, we construct smooth traveling counter-rotating vortex pairs with circular supports for the generalized surface quasi-geostrophic equation. These vortex pairs are analogues of the Lamb dipoles for the 2D incompressible Euler equation. The solutions are obtained by maximization of the energy over some appropriate classes of admissible functions. We establish the uniqueness of maximizers and compactness of maximizing sequences in our variational setting. Using these facts, we further prove the orbital stability of the circular vortex pairs for the generalized surface quasi-geostrophic equation.
Immune Reconstitution Bone Loss Exacerbates Bone Degeneration Due to Natural Aging in a Mouse Model
Authors: Weitzmann M Neale , Weiss Daiana , Vikulina Tatyana , Roser-Page Susanne , Yu Kanglun , McGee-Lawrence Meghan E , Tu Chia Ling , Chang Wenhan , Ofotokun Ighovwerha
Published: December 2021

Background

Immune reconstitution bone loss (IRBL) is a common side-effect of antiretroviral therapy (ART) in people with human immunodeficiency virus (PWH). Immune reconstitution bone loss acts through CD4+ T-cell/immune reconstitution-induced inflammation and is independent of antiviral regimen. Immune reconstitution bone loss may contribute to the high rate of bone fracture in PWH, a cause of significant morbidity and mortality. Although IRBL is transient, it remains unclear whether bone recovers, or whether it is permanently denuded and further compounds bone loss associated with natural aging.

Methods

We used a validated IRBL mouse model involving T-cell reconstitution of immunocompromised mice. Mice underwent cross-sectional bone phenotyping of femur and/or vertebrae between 6 and 20 months of age by microcomputed tomography (µCT) and quantitative bone histomorphometry. CD4+ T cells were purified at 20 months to quantify osteoclastogenic/inflammatory cytokine expression.

Results

Although cortical IRBL in young animals recovered with time, trabecular bone loss was permanent and exacerbated skeletal decline associated with natural aging. At 20 months of age, reconstituted CD4+ T cells express enhanced osteoclastogenic cytokines including RANKL, interleukin (IL)-1β, IL-17A, and tumor necrosis factor-α, consistent with elevated osteoclast numbers.

Conclusions

Immune reconstitution bone loss in the trabecular compartment is permanent and further exacerbates bone loss due to natural aging. If validated in humans, interventions to limit IRBL may be important to prevent fractures in aging PWH.
Rapid Identification of Peucedanum praeruptorum Dunn and Its Adulterants by Hand-Held Near-Infrared Spectroscopy
Authors: Wang Fang , Jia Bin , Song Xiangwen , Dai Jun , Li Xiaoli , Gao Haidi , Pan Haoyu , Yan Hui , Han Bangxing
Published: December 2021

Background

Peucedanum praeruptorum Dunn (PPD) is a traditional Chinese medical herb of high medical and economic value. However, PPD is often adulterated by inexpensive plants.

Objective

In order to establish an integrated and straightforward methodology to identify adulterated PPD products, hand-held near-infrared spectroscopy (NIRS) combined with chemical pattern recognition techniques was employed.

Method

The standard normal variate (SNV) was used to preprocess the original near-infrared spectra. Principal component analysis (PCA), linear discriminant analysis (LDA), and partial least-squares regression analysis (PLSDA) were used to construct the recognition models.

Results

PCA analysis could not correctly distinguish PPD from non-PPD. However, based on absorbance in the spectral region of 1405–2442 nm and SNV pretreatment, the accuracy of the LDA model was above 90% at identifying genuine PPD. Compared with the LDA method, the PLSDA model is more stable and reliable, and its model prediction accuracy was 93.4%.

Conclusion

The combination of NIRS and chemometric methods based on a hand-held near-infrared spectrometer is an efficient, nondestructive, and reliable method for validating traditional Chinese medicine PPD.

Highlights

The advanced method based on a hand-held near-infrared spectrometer can be used for rapid identification and quality evaluation of PPD in the field, medicinal material markets, and points of sale.