bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized HLA typing leads to the discovery of novel HLA alleles and tumor‐specific HLA variants
Authors: Anzar Irantzu , Sverchkova Angelina , Samarakoon Pubudu , Ellingsen Espen Basmo , Gaudernack Gustav , Stratford Richard , Clancy Trevor
Published: January 2022

Accurate and full‐length typing of the HLA region is important in many clinical and research settings. With the advent of next generation sequencing (NGS), several HLA typing algorithms have been developed, including many that are applicable to whole exome sequencing (WES). However, most of these solutions operate by providing the closest‐matched HLA allele among the known alleles in IPD‐IMGT/HLA Database. These database‐matching approaches have demonstrated very high performance when typing well characterized HLA alleles. However, as they rely on the completeness of the HLA database, they are not optimal for detecting novel or less well characterized alleles. Furthermore, the database‐matching approaches are also not adequate in the context of cancer, where a comprehensive characterization of somatic HLA variation and expression patterns of a tumor's HLA locus may guide therapy and clinical outcome, because of the pivotal role HLA alleles play in tumor antigen recognition and immune escape. Here, we describe a personalized HLA typing approach applied to WES data that leverages the strengths of database‐matching approaches while simultaneously allowing for the discovery of novel HLA alleles and tumor‐specific HLA variants, through the systematic integration of germline and somatic variant calling. We applied this approach on WES from 10 metastatic melanoma patients and validated the HLA typing results using HLA targeted NGS sequencing from patients where at least one HLA germline candidate was detected on Class I HLA. Targeted NGS sequencing confirmed 100% performance for the 1st and 2nd fields. In total, five out of the six detected HLA germline variants were because of Class I ambiguities at the third or fourth fields, and their detection recovered the correct HLA allele genotype. The sixth germline variant let to the formal discovery of a novel Class I allele. Finally, we demonstrated a substantially improved somatic variant detection accuracy in HLA alleles with a 91% of success rate in simulated experiments. The approach described here may allow the field to genotype more accurately using WES data, leading to the discovery of novel HLA alleles and help characterize the relationship between somatic variation in the HLA region and immunosurveillance.
A uniform treatment of Grothendieck's localization problem
Authors: Murayama Takumi
Published: January 2022

Let $f\colon Y \to X$ be a proper flat morphism of locally noetherian schemes. Then the locus in $X$ over which $f$ is smooth is stable under generization. We prove that, under suitable assumptions on the formal fibers of $X$, the same property holds for other local properties of morphisms, even if $f$ is only closed and flat. Our proof of this statement reduces to a purely local question known as Grothendieck's localization problem. To answer Grothendieck's problem, we provide a general framework that gives a uniform treatment of previously known cases of this problem, and also solves this problem in new cases, namely for weak normality, seminormality, $F$-rationality, and the ‘Cohen–Macaulay and $F$-injective’ property. For the weak normality statement, we prove that weak normality always lifts from Cartier divisors. We also solve Grothendieck's localization problem for terminal, canonical, and rational singularities in equal characteristic zero.
El cuerpo femenino fotografiado por mujeres artistas
Authors: Rosales Cueva José Horacio , Nuñez Arce Beatriz
Published: January 2022

Este artículo expone parte de los resultados de una investigación semiótica de la representación del cuerpo en la fotografía creada entre 2010 y 2020 por artistas latinoamericanas. Los objetivos de la pesquisa son comprender y modelizar cómo es configurada la corporeidad femenina en la fotografía digital de creadoras que, específicamente, emplean medios virtuales para divulgar las propias obras. El método de investigación cualitativo-interpretativo se encaminó al estudio de casos que correlaciona fotógrafa, fotografía y medios digitales. El procedimiento analítico se realizó con la semiótica visual que aborda los elementos figurativos y narrativos de las imágenes y enfatiza las prácticas enunciativas en entornos socioculturales de intercambio de objetos significantes. Los resultados del estudio de cada imagen seleccionada y constituyente de la muestra investigada llevaron a construir una teoría fundamentada que engloba las convergencias de elaboración y divulgación de las fotografías de la muestra. Este artículo expone los resultados de tal procedimiento practicado con unas esas imágenes, Sin título, que integra la serie fotográfica elaborada por Victoria Razo sobre las marchas de mujeres del 8 de marzo de 2020 en Ciudad de México. El análisis semiótico realizado aporta recursos a la comprensión de prácticas enunciativas visuales en escenarios de reivindicaciones sociales y permite algunas conclusiones sobre la iconografía, con atributos del hacer documental y artístico, del cuerpo-sujeto de mujer, mientras que las creadoras aprovechan los medios digitales para la exhibición artística y dinamizar la comprensión del observador de las gestas reivindicativas de los derechos femeninos.
Impact of the COVID-19 pandemic on uveitis patient care
Authors: Vu Alexander F , Kodati Shilpa , Lin Phoebe , Bodaghi Bahram , Emami-Naeini Parisa
Published: January 2022

Background

The COVID-19 pandemic has significantly changed practice of medicine and patient care worldwide. The impact of the pandemic on patients with uveitis is unknown. We developed the COVID-19 Practice Patterns Study Group to evaluate the effect of the pandemic on uveitis patient care.

Methods

This is a multicentre, cross-sectional survey of uveitis specialists practising worldwide. A web-based survey was distributed through the mailing lists of international uveitis societies to assess modifications in patient care, and use of immunomodulatory therapies (IMTs),aswell as considerations regarding COVID-19 vaccination.

Results

A diverse group consisting of 187 uveitis specialists from six continents participated in this survey. Most of these experts noted a disruption in clinical management of patients, including clinic closures or decrease in volume, patients missing in-person visits due to the fear of infection and difficulties obtaining laboratory testing. Most participants initiated (66.8%) and continued (93.3%) IMTs based on clinical presentation and did not modify their use of immunosuppressives. In cases of reported exposure to COVID-19 infection, most participants (65.3%) recommended no change in IMTs. However, 73.0% of the respondents did recommend holding all or select IMTs in case of COVID-19 infection. COVID-19 vaccine was recommended universally by almost all the specialists and 52% stated that they would counsel patients regarding the decreased immunogenicity and effectiveness of the vaccine in immunocompromised patients.

Conclusions

Uveitis patient care has changed significantly since the beginning of the pandemic. The recommendations will continue to evolve as new data on IMTs and vaccination become available.
Individual, parental and built environmental features as influencing factors of active travel to school in northeast China: findings from a cross-sectional study
Authors: Wang Yinuo , Liu Yang , Song Shenzhi , Gittelsohn Joel , Ouellette Miranda , Ma Yanan , Wen Deliang
Published: January 2022

Objectives

Active travel to school (ATS)-associated factors had been studied in some developed countries but rarely in China. We studied the associated factors of ATS at individual, parental and built environment domains in northeast China.

Design and participants

A cross-sectional survey was conducted among 4–6 grade students in 2017. Sociodemographic features and information of parents were collected using questionnaires, and SuperMap (a geographical information system software) was used to catch built environment features. Logistic regression models were used to examine the relationship between multilevel factors and ATS.

Results

Our study sample comprised 3670 primary school students aged from 8 to 15 (boys=51.0%, ATS=48.8%). Perceived to be fat (OR 1.25, 95% CI 1.00 to 1.55, p<0.05), feeling easy to walk for a short distance (OR 1.63, 95% CI 1.21 to 2.20, p<0.05), mother unemployed (OR 1.52, 95% CI 1.13 to 2.06, p<0.05), higher land use mix (OR 1.23, 95% CI 1.11 to 1.37, p<0.001) and higher density of public transport stations (OR 1.22, 95% CI 1.09 to 1.37, p<0.05) were positively associated with increased possibility of ATS, while higher household annual income (OR 0.60, 95% CI 0.44 to 0.83, p<0.05) and possession of private vehicles (OR 0.56, 95% CI 0.45 to 0.69, p<0.001) were negatively associated with possibility of ATS.

Conclusions

The significant factors associated with ATS were at every examined level, which implies multilevel interventions are needed to encourage ATS. Further interventions could focus on the children’s willingness to lead students to opt for healthy behaviours, and children from wealthier families should be encouraged to choose ATS. Also, the government should improve built environment walkability so as to encourage ATS.
Impact of the COVID-19 pandemic on the experience and mental health of university students studying in Canada and the UK: a cross-sectional study
Authors: Appleby Jennifer A , King Nathan , Saunders Kate E , Bast Anne , Rivera Daniel , Byun Jin , Cunningham Simone , Khera Charandeep , Duffy Anne C
Published: January 2022

Objectives

To explore the impact of the COVID-19 pandemic on the experiences and mental health of university students.

Design

A cross-sectional study consisting of an electronic survey about students’ experiences and concerns during the pandemic and the associated impact. In addition to the quantitative analysis, free-text responses were extracted and analysed using a framework technique.

Setting

Queen’s University in Canada and the University of Oxford in the UK.

Participants

Undergraduate students at Queen’s University and first-year undergraduate students at the University of Oxford were invited to complete the COVID-19 supplement survey. This study included data from 3013 Queen’s students as the primary focus and 339 Oxford students as a secondary comparison.

Results

Females at Queen’s reported greater adherence to government recommendations to prevent the spread of COVID-19 (91.3% vs 86.7%, χ2 p<0.01) and were more likely to self-isolate (63.9% vs 57.0%, χ2 p<0.01) than males. A similar trend was seen among Oxford students. Students’ concerns were wide ranging including those related to their learning experience, finances and future academic and career prospects. 78.9% of Queen’s students and 50.4% of first-year Oxford students reported worries about the long-term impact on their academic and job prospects. A sizeable proportion of students also reported that the pandemic negatively impacted their plans to continue at university (29.4% of Queen’s, 14.2% of Oxford) and disrupted activities important to their mental well-being. Key themes identified in the qualitative component included the negative impacts of social isolation, challenging academic changes and disruption to support services and means of coping.

Conclusions

Overall, findings underscore the importance of addressing areas of student concern and the aspects of student life negatively impacted by the pandemic in order to maintain student well-being and support a successful university experience.
Creating accountable hospital service areas in China: a case analysis of health expenditure in the metropolis of Chengdu
Authors: Cao Peiya , Zhao Xiaoshuang , Yang Yili , Pan Jay
Published: January 2022

Objectives

To delineate hospital service areas (HSAs) using the Dartmouth approach in China and identify the hypothesised demand-side, supply-side and region-specific factors of health expenditure within HSAs.

Design

Population-based descriptive study.

Setting

We selected the metropolis of Chengdu, one of the three most populous cities in China as a case for the analysis, where approximately 16.33 million residents living.

Participants

Individual-level in-patient discharge records (n=904 298) during the fourth quarter of 2018 (from 1 September to 31 December) were extracted from Sichuan Health Commission. Cases of non-residents of Chengdu were excluded from the datasets.

Methods

We conducted three sets of analyses: (1) apply Dartmouth approach to delineate HSAs; (2) use Geographic Information System (GIS)-based method to demonstrate health expenditure variations across delineated HSAs and (3) employ a three-level multilevel linear model to examine the association between health expenditure and demand-side, supply-side and region-specific factors.

Results

A total of 113 HSAs with a median population of 60 472 (ranging from 7022 to 827 750) was delineated. Total in-patient expenditure per admission varied more than threefold across HSAs after adjusting for age and gender. Apart from a list of demand-side factors, an increased number of physicians, healthcare facilities at higher levels and for-profit healthcare facilities were significantly associated with increased total in-patient expenditures. At the HSA level, the proportion of private healthcare facilities located in a single HSA was associated with increased total in-patient expenditure generated by that HSA, while the increased number of healthcare facilities in a HSA was negatively associated with the total in-patient expenditures.

Conclusion

HSAs were delineated to help establish an accountable healthcare delivery system, which serves as local hospital markets to provide in-patient healthcare via connecting demanders with suppliers inside particular HSAs. Policy-makers should adopt HSAs to identify variations of total in-patient expenditures among different areas and the potential associated factors. Findings from the HSA-based analysis could inform the formulation of relevant health policies and the optimisation of healthcare resource allocations.
Targeting pancreatic cancer by TAK-981: a SUMOylation inhibitor that activates the immune system and blocks cancer cell cycle progression in a preclinical model
Authors: Kumar Sumit , Schoonderwoerd Mark J A , Kroonen Jessie S , de Graaf Ilona J , Sluijter Marjolein , Ruano Dina , González-Prieto Román , Verlaan-de Vries Matty , Rip Jasper , Arens Ramon , de Miranda Noel F C C , Hawinkels Lukas J A C , van Hall Thorbald , Vertegaal Alfred C O
Published: January 2022

Objective

Pancreatic ductal adenocarcinoma (PDAC) has the characteristics of high-density desmoplastic stroma, a distinctive immunosuppressive microenvironment and is profoundly resistant to all forms of chemotherapy and immunotherapy, leading to a 5-year survival rate of 9%. Our study aims to add novel small molecule therapeutics for the treatment of PDAC.

Design

We have studied whether TAK-981, a novel highly selective and potent small molecule inhibitor of the small ubiquitin like modifier (SUMO) activating enzyme E1 could be used to treat a preclinical syngeneic PDAC mouse model and we have studied the mode of action of TAK-981.

Results

We found that SUMOylation, a reversible post-translational modification required for cell cycle progression, is increased in PDAC patient samples compared with normal pancreatic tissue. TAK-981 decreased SUMOylation in PDAC cells at the nanomolar range, thereby causing a G2/M cell cycle arrest, mitotic failure and chromosomal segregation defects. TAK-981 efficiently limited tumour burden in the KPC3 syngeneic mouse model without evidence of systemic toxicity. In vivo treatment with TAK-981 enhanced the proportions of activated CD8 T cells and natural killer (NK) cells but transiently decreased B cell numbers in tumour, peripheral blood, spleen and lymph nodes. Single cell RNA sequencing revealed activation of the interferon response on TAK-981 treatment in lymphocytes including T, B and NK cells. TAK-981 treatment of CD8 T cells ex vivo induced activation of STAT1 and interferon target genes.

Conclusion

Our findings indicate that pharmacological inhibition of the SUMO pathway represents a potential strategy to target PDAC via a dual mechanism: inhibiting cancer cell cycle progression and activating anti-tumour immunity by inducing interferon signalling.
Public rescue tube deployment in Hawaii: protective association with rescuer drownings
Authors: Velasco Bridget , Galanis Daniel J , Bronstein Alvin C , Downs Monty
Published: January 2022

Objective

To describe the association between public rescue tube (PRT) flotation devices and fatal rescuer drownings in Kauai, Hawaii.

Methods

We reviewed Hawaii death certificate data from 1993 to 2017, sometimes supplemented with autopsy and emergency medical service reports, to identify fatal rescuer drownings. Incidents were analysed in relation to the initial 2008 deployment of PRT.

Results

Over the 25-year period, only 13% (228) of the 1750 identified drownings occurred in Kauai, but nearly half (46%, or 13) of the 28 rescuer deaths occurred there. However, only 1 of the 13 rescuer deaths in Kauai occurred after the 2008 deployment of PRT. The state-wide proportion of rescuer deaths in Kauai decreased significantly from 60% (12 of 20) from 1993 to 2007 to 13% (1 of 8) from 2008 to 2017. There were no apparent changes in the proportions of rescuer drownings in the other three counties of the state, where PRTs were essentially non-existent.

Conclusion

Despite valid concerns, we found no fatal rescuer drownings related to PRT use after their 2008 introduction in the county of Kauai. Instead, we observed a reduction in the number of rescuer drownings, and in their proportion of total drownings in association with the deployment of PRT. The findings of this study have the potential to directly impact ocean and other open water environment-related fatal drowning prevention policy and practice.
Evaluation of the in vivo and in vitro anti-inflammatory activity of a new hybrid NSAID tetrahydropyran derivative
Authors: Gonçalves Gabriela Mastrangelo , de Oliveira Joyce Mattos , Ferreira da Costa Fernandes Thayane , Laureano-Melo Roberto , da Silva Côrtes Wellington , Capim Saulo Luis , Araujo de Almeida Vasconcellos Mário Luiz , Guimarães Marinho Bruno
Published: January 2022

Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(±)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro-2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-α, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.
Concerning pion parton distributions
Authors: Cui Z.-F. , Ding M. , Morgado J. M. , Raya K. , Binosi D. , Chang L. , Papavassiliou J. , Roberts C. D. , Rodríguez-Quintero J. , Schmidt S. M.
Published: January 2022

Analyses of the pion valence-quark distribution function (DF), "Equation missing", which explicitly incorporate the behaviour of the pion wave function prescribed by quantum chromodynamics (QCD), predict "Equation missing", $$\beta (\zeta \gtrsim m_p)>2$$

β
(
ζ
≳

m
p

)
>
2

, where $$m_p$$

m
p

is the proton mass. Nevertheless, more than forty years after the first experiment to collect data suitable for extracting the $$x\simeq 1$$

x
≃
1

behaviour of "Equation missing", the empirical status remains uncertain because some methods used to fit existing data return a result for "Equation missing" that violates this constraint. Such disagreement entails one of the following conclusions: the analysis concerned is incomplete; not all data being considered are a true expression of qualities intrinsic to the pion; or QCD, as it is currently understood, is not the theory of strong interactions. New, precise data are necessary before a final conclusion is possible. In developing these positions, we exploit a single proposition, viz. there is an effective charge which defines an evolution scheme for parton DFs that is all-orders exact. This proposition has numerous corollaries, which can be used to test the character of any DF, whether fitted or calculated.
Strong coupling constant from moments of quarkonium correlators revisited
Authors: Petreczky Peter , Weber Johannes Heinrich
Published: January 2022

We revisit previous determination of the strong coupling constant from moments of quarkonium correlators in (2 + 1)-flavor QCD. We use previously calculated moments obtained with Highly Improved Staggered Quark (HISQ) action for five different quark masses and several lattice spacings. We perform a careful continuum extrapolations of the moments and from the comparison of these to the perturbative result we determine the QCD Lambda parameter, $$\varLambda _{\overline{MS}}^{n_f=3}=332 \pm 17 \pm 2(scale)$$

Λ

MS

¯

n
f

=
3

=
332
±
17
±
2

(
s
c
a
l
e
)

MeV. This corresponds to $$\alpha _s^{n_f=5}(\mu =M_Z)=0.1177(12)$$

α
s

n
f

=
5

(
μ
=

M
Z

)

=
0.1177

(
12
)

.
Thermoelectric transport coefficients of quark matter
Authors: Abhisek Aman , Das Arpan , Kumar Deepak , Mishra Hiranmaya
Published: January 2022

A thermal gradient and/or a chemical potential gradient in a conducting medium can lead to an electric field, an effect known as thermoelectric effect or Seebeck effect. In the context of heavy-ion collisions, we estimate the thermoelectric transport coefficients for quark matter within the ambit of the Nambu–Jona Lasinio (NJL) model. We estimate the thermal conductivity, electrical conductivity, and the Seebeck coefficient of hot and dense quark matter. These coefficients are calculated using the relativistic Boltzmann transport equation within relaxation time approximation. The relaxation times for the quarks are estimated from the quark–quark and quark–antiquark scattering through meson exchange within the NJL model. As a comparison to the NJL model estimation of the Seebeck coefficient, we also estimate the Seebeck coefficient within a quasiparticle approach.
Impact and dynamics of hate and counter speech online
Authors: Garland Joshua , Ghazi-Zahedi Keyan , Young Jean-Gabriel , Hébert-Dufresne Laurent , Galesic Mirta
Published: January 2022

Citizen-generated counter speech is a promising way to fight hate speech and promote peaceful, non-polarized discourse. However, there is a lack of large-scale longitudinal studies of its effectiveness for reducing hate speech. To this end, we perform an exploratory analysis of the effectiveness of counter speech using several different macro- and micro-level measures to analyze 131,366 political conversations that took place on German Twitter over four years. We report on the dynamic interactions of hate and counter speech over time and provide insights into whether, as in ‘classic’ bullying situations, organized efforts are more effective than independent individuals in steering online discourse. Taken together, our results build a multifaceted picture of the dynamics of hate and counter speech online. While we make no causal claims due to the complexity of discourse dynamics, our findings suggest that organized hate speech is associated with changes in public discourse and that counter speech—especially when organized—may help curb hateful rhetoric in online discourse.
Three-sheeted Riemann surface and solutions of the Itoh–Narita–Bogoyavlensky lattice hierarchy
Authors: Geng Xianguo , Wei Jiao
Published: January 2022

The Itoh–Narita–Bogoyavlensky lattice hierarchy associated with a discrete [Formula: see text] matrix spectral problem is derived by using Lenard recursion equations. Resorting to the characteristic polynomial of Lax matrix for the lattice hierarchy, we introduce a three-sheeted Riemann surface [Formula: see text] of arithmetic genus [Formula: see text] and construct the corresponding Baker–Akhiezer function and meromorphic function on it. On the basis of the theory of Riemann surface, the continuous flow and discrete flow related to the lattice hierarchy are straightened with the help of the Abel map. Quasi-periodic solutions of the lattice hierarchy in terms of the Riemann theta function are constructed by using the asymptotic properties and the algebro-geometric characters of the meromorphic function and Riemann surface.
Image Stripe Noise Removal Based on Compressed Sensing
Authors: Zhang Yan , Li Jie , Li Xinyue , Wang Bin , Li Tiange
Published: January 2022

The sensors or electronic components are vulnerable to interference in the camera’s imaging process, usually leading to random directional stripes. Therefore, a method of stripe noise removal based on compressed sensing is proposed. First, the measurement matrix of the image with stripe noise is established, which makes the stripe images equivalent to the observation of the original image. Second, the relationships between the corresponding coefficients of adjacent scales are defined. On this basis, the bivariate threshold function is set in the curvelet sparse domain to represent the features of images. Finally, the Landweber iteration algorithm of alternating convex projection and filtering operation is achieved. Furthermore, to accelerate the noise removal at the initial stage of iteration and preserve the image details later, the exponential threshold function is utilized. This method does not need many samples, which is different from the current deep learning method. The experimental results show that the proposed algorithm represents excellent performance in removing the stripes and preserving the texture details. In addition, the PSNR of the denoised image has been dramatically improved compared with similar algorithms.
Border Collision Bifurcations and Chaos in a Ring of Three Unidirectionally Coupled Nonmonotonic Piecewise Constant Neurons
Authors: Horikawa Yo
Published: January 2022

The bifurcations and chaos in a ring of three nonmonotonic piecewise constant neurons with unidirectional inhibitory coupling are examined. Periodic solutions in the system undergo border collision bifurcations, which are characteristic of piecewise smooth systems. Conditions for the bifurcations of periodic solutions are derived analytically by using a piecewise constant function as the output function of neurons. Multiple periodic solutions are generated through border collision bifurcations and saddle-node bifurcations. Chaotic attractors are generated through border collision bifurcations and degenerate period-doubling bifurcations. The existence of multiple periodic solutions and chaotic attractors is proven to be common in rings of unidirectionally coupled nonmonotonic neurons.
Vibration Analysis of an In-Pipe Inspection Robot Considering Fluid-Structure Coupling
Authors: Zhang Hang , Gao Mengqi , Li Zhenlin , Wu Qibing
Published: January 2022

A fluid drive in-pipe inspection robot is an essential device for the inner inspection of long-distance oil and gas pipelines. Obstacles such as dents and welds can significantly affect the operation stability of the robot as well as the accuracy of inspection. In this paper, a dynamic model is created to investigate the vibrational response of an in-pipe inspection robot moving through a dented pipe. A mechanical model of the polyurethane sealing disc is established based on the Kelvin spring damping model to simulate its bending deformation. Using the simplified model of the in-pipe inspection robot, the axial vibration equation of the robot is analyzed in detail. Furthermore, a dynamic simulation of the virtual prototype of the in-pipe inspection robot is conducted using the MSC/ADAMS software, considering the interaction between the fluid and the structure. Then, the effects of the robot’s speed, sealing disc interval, and dent height on the vibration response during the pigging are examined. The results indicate that the faster the in-pipe inspection robot passes over the pipe dents, the higher the axial vibration generated by the robot, while the time needed for returning to the stable state is shorter. The pitch vibration caused by the dent substantially intensifies with an increase in the sealing disc interval. The axial and pitch vibration caused by the dent intensify significantly with increasing the dent height. The results obtained herein should prove useful to the optimization of the structural design and precise positioning of the in-pipe inspection robot.
Advances in Molecular Modeling of Ion-Protein Interaction Systems Towards Accurate Electrostatics: Methods and Applications
Authors: Shen Lingling
Published: January 2022

Metal ions are ubiquitous in complex with proteins and play key roles in protein structure and function. The ion-protein interactions are electrostatic delicate in nature, however, the description of electrostatic interactions could be problematic in conventional additive fixed-charge force fields. With empowered computational sources going beyond the common approximations, many efforts have been done to take account in more elaborate electrostatic description in molecular modeling using more sophisticated physical models and dilated algorithms/implementations. Here we review rencent progress in advanced polarizable models and new impletment approaches towards accurate electrostatics and highlight some successful application cases in ion-protein interaction systems in recent years.
Structure, Spectroscopic Investigation, Molecular Docking andIn vitroCytotoxicity Studies on 4,7-dihydroxycoumarin: A Breast Cancer Drug
Authors: Ramuthai M. , Jeyavijayan S. , Premkumar R. , Uma Priya M. , Jayram Naidu Dhanpal
Published: January 2022

Coumarin derivatives are broadly used as anti-inflammatory, antioxidants, anticancer, and antiviral drugs in recent years. In particular, hydroxy coumarins have great importance because of their various biological and pharmacological purposes. The quantum chemical studies of 4,7-dihydroxycoumarin (DHC) have been performed using the cc-pVTZ level of basis set. The DHC molecular structure has been optimized and the computed frequency assignments have been correlated well with the experimental results. The experimental [Formula: see text]C NMR shifts of DHC have been compared with the computed [Formula: see text]C NMR in the dimethyl sulfoxide (DMSO) solution using the Gauge-invariant atomic orbital (GIAO) method. The electron delocalization within the DHC is shown by highest occupied molecular orbitals (HOMO)-lowest unoccupied molecular orbitals (LUMO) energy analysis, and the resulting small energy gap value reveal the molecule’s bioactive characteristics. The natural bond orbital (NBO) analysis approves the bioactive property of the DHC molecule. The DHC compound has a cytotoxic impact on the MCF-7 breast cancer cell line, according to in vitro cytotoxicity studies. The docking study approves that the DHC works as a new inhibitor of breast cancer targeted proteins such as epidermal growth factor receptor (EGFR), estrogen receptor (ER), and progesterone receptor (PR). Thus, this work covers the approach for the evolution of new drugs against breast cancer.
Bored log-grounds by teredinid bivalves in marine deposits from the Monos Formation (Upper Cretaceous) in central Cuba
Authors: Villegas-Martín Jorge , Serrano-Brañas Claudia Inés , Rojas-Consuegra Reinaldo , Arano-Ruiz Alberto , Verde Mariano , Borges-Sellen Carlos Rafael
Published: January 2022

Borings of
Apectoichnus longissimus
and
Teredolites clavatus
are described from wood fragments preserved in sandstone deposits of the Maastrichtian (Upper Cretaceous) Monos Formation in central Cuba. In addition, palaeobiological, palaeoecological and taphonomic implications of these are inferred. The borings are interpreted as mainly produced by Teredinid marine bivalves, which inhabited driftwood substrates. The taphonomic features such as mode of occurrence, density and position of the borings within the relict log-grounds suggest: (i) post-burial compaction of the xylic substrates by the surrounding sediments during burial, (ii) different ontogenetic stages and colonization episodes of teredinids on the studied wood fragments and (iii) different residence time of the wood fragments floating or near the sediment–water interface. Furthermore, the accumulation of wood fragments with
A
.
longissimus
and
T
.
clavatus
in the shallow marine deposits of the Monos Formation was probably the result of a marine transgression event in these deposits, thus leaving them exposed to attack by teredinid larvae. This study explores the life histories and taphonomic histories of teredinid bivalves and wood fragments in the Monos Formation, adding to the literature on ichnofossils in this lithostratigraphic unit.
Designing UIs for static-analysis tools
Authors: Tiganov Daniil , Do Lisa Nguyen Quang , Ali Karim
Published: January 2022

Evaluating tool design guidelines with SWAN.
Computing Contingent Plan Graphs using Online Planning
Authors: Maliah Shlomi , Komarnitski Radimir , Shani Guy
Published: January 2022

In contingent planning under partial observability with sensing actions, agents actively use sensing to discover meaningful facts about the world. Recent successful approaches translate the partially observable contingent problem into a non-deterministic fully observable problem, and then use a planner for non-deterministic planning. However, the translation may become very large, encumbering the task of the non-deterministic planner. We suggest a different approach—using an online contingent solver repeatedly to construct a plan tree. We execute the plan returned by the online solver until the next observation action, and then branch on the possible observed values, and replan for every branch independently. In many cases a plan tree can have an exponential width in the number of state variables, but the tree may have a structure that allows us to compactly represent it using a directed graph. We suggest a mechanism for tailoring such a graph that reduces both the computational effort and the storage space. Our method also handles non-deterministic domains, by identifying cycles in the plans. We present a set of experiments, showing our approach to scale better than state-of-the-art offline planners.
The trouble with Facebook
Authors: Hong Jason
Published: January 2022

The
Communications
website, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Jason Hong considers how computer scientists, technologists could help guide regulation of the social media giant.
Supporting people with autism spectrum disorders in the exploration of PoIs
Authors: Mauro Noemi , Ardissono Liliana , Cena Federica
Published: January 2022

The suggestion of Points of Interest (PoIs) to people with autism spectrum disorders challenges the research about recommender systems by introducing an explicit need to consider both user preferences and aversions in item evaluation. The reason is that autistic users' perception of places is influenced by sensory aversions, which can cause stress and anxiety when they visit the suggested PoIs. Therefore, the management of individual preferences is not enough to provide these people with suitable recommendations.

To address this issue, we propose a Top-N recommendation model that combines information about the user's idiosyncratic aversions with her/his preferences in a personalized way. The goal is that of suggesting the places that (s)he can like and smoothly experience at the same time. We are interested in finding a user-specific balance of compatibility and interest within a recommendation model that integrates heterogeneous evaluation criteria to appropriately take these aspects into account.

We tested our model on 148 adults, 20 of which were people with autism spectrum disorders. The evaluation results show that, on both groups, our model achieves superior accuracy and ranking results than the recommender systems based on item compatibility, on user preferences, or which integrate these aspects using a uniform evaluation model. These findings encourage us to use our model as a basis for the development of inclusive recommender systems.
Is your autonomous vehicle as smart as you expected?
Authors: Tu Yu-Ju (Tony) , Shang Shari S. , Wu Junyi
Published: January 2022

Suggesting a better route to evaluate autonomous vehicles' smartness.
Data science meets law
Authors: Hod Shlomi , Chagal-Feferkorn Karni , Elkin-Koren Niva , Gal Avigdor
Published: January 2022

Learning Responsible AI together.
Becoming universal
Authors: Haigh Thomas
Published: January 2022

A new history of modern computing.
Precision Medicine in Low- and Middle-Income Countries
Authors: Radich Jerald P. , Briercheck Edward , Chiu Daniel T. , Menon Manoj P. , Sala Torra Olga , Yeung Cecilia C.S. , Warren Edus H.
Published: January 2022

Most cancer cases occur in low- and middle-income countries (LMICs). The sophisticated technical and human infrastructure needed for optimal diagnosis, treatment, and monitoring of cancers is difficult enough in affluent countries; it is especially challenging in LMICs. In Western, educated, industrial, rich, democratic countries, there is a growing emphasis on and success with precision medicine, whereby targeted therapy is directed at cancers based on the specific genetic lesions in the cancer. Can such precision approaches be delivered in LMICs? We offer some examples of novel partnerships and creative solutions that suggest that precision medicine may be possible in LMICs given heavy doses of will, creativity, and persistence and a little luck.
Application of a Solid Bismuth Microelectrode in an Adsorptive Stripping Voltammetric Procedure of Trace Tin Quantification
Authors: Adamczyk Marzena , Grabarczyk Malgorzata
Published: January 2022

A novel solid bismuth microelectrode in combination with adsorptive stripping voltammetry is demonstrated as a simple and fast method for determination of tin. The proposed method includes the formation of a tin complex with cupferron in the solution and deposition on the solid bismuth microelectrode. The selection of the most optimal parameters determining the sensitivity of the elaborated procedure was made. Under optimized parameters (pH = 4.6; acetate buffer concentration: 0.1 mol l−1; cupferron concentration: 2 × 10−4 mol l−1; activation potential/time: −2.5 V/5 s; deposition potential/time: −0.6 V/40 s), a linear response of Sn(II) in the concentration range of 8 × 10−9 do 8 × 10−7 mol l−1 (r = 0.9984) was obtained with a detection limit of 2.1 × 10−9 mol l−1. The interferences of foreign ions and organic matrix of environmental water samples were carefully studied. The accuracy of the method was studied by analyzing certified reference materials SPS-WW1 Waste Water and SPS-SW1 Surface Water as well as Bystrzyca river and rain water, and passable results were obtained.
Estradiol and RSPO3 regulate vertebral trabecular bone mass independent of each other
Authors: Nilsson Karin H. , Wu Jianyao , Gustafsson Karin L. , El Shahawy Maha , Koskela Antti , Tuukkanen Juha , Tuckermann Jan , Henning Petra , Lerner Ulf H. , Ohlsson Claes , Movérare-Skrtic Sofia
Published: January 2022

Osteoblast-derived RSPO3 is known to be a crucial regulator of vertebral trabecular bone. Our new findings show that RSPO3 and estrogen regulate trabecular bone independent of each other, but that RSPO3 is necessary for a complete estrogenic effect on cortical bone.
Nrf2 signaling in heart failure: expression of Nrf2, Keap1, antioxidant, and detoxification genes in dilated or ischemic cardiomyopathy
Authors: Lu Yingying , An Lingling , Taylor Matthew R. G. , Chen Qin M.
Published: January 2022

Increased levels of oxidative stress have been found with heart failure. Whether failing hearts express antioxidant and detoxification enzymes have not been addressed systematically. Nrf2 gene encodes a transcription factor that regulates the expression of antioxidant and detoxification genes. Using RNA-Seq data set from explanted hearts of 37 patients with dilated cardiomyopathy (DCM), 13 patients with ischemic cardiomyopathy (ICM), and 14 nonfailure (NF) donors as a control, we addressed whether failing hearts change the expression of Nrf2, its negative regulator Keap1, and antioxidant or detoxification genes. Significant increases in the ratio of Nrf2 to Keap1 were found to associate with DCM or ICM. Antioxidant genes showed decreased expression in both types of heart failure, including NQO1, SOD1, GPX3, GPX4, GSR, PRDX1, and TXNRD1. Detoxification enzymes, GCLM and EPHX1, also showed decreased expression, whereas the CYP1B1 transcript was elevated in both DCM and ICM. The genes encoding metal-binding protein ferritin were decreased, whereas five out of 12 metallothionein genes showed elevated expression. Our finding on Nrf2 gene expression has been validated by meta-analysis of seven independent data sets of microarray or RNA-Seq for differential gene expression in DCM and ICM from NF controls. In conclusion, minor elevation of Nrf2 gene expression is not coupled to increases in antioxidant and detoxification genes, supporting an impairment of Nrf2 signaling in patients with heart failure. Decreases in multiple antioxidant and detoxification genes are consistent with the observed increases of oxidative stress in failing hearts.
Integrated analysis of transcriptome profiling of lncRNAs and mRNAs in livers of type 2 diabetes mellitus
Authors: Lan Xi , Han Jing , Wang Binxian , Sun Mingzhu
Published: January 2022

Long noncoding RNAs (lncRNAs) influence the progression of almost all human diseases, but the participation of lncRNAs in type 2 diabetes mellitus (T2DM) has not been fully elucidated. This study aimed to systematically compare the transcriptome profiling of lncRNAs and mRNAs in livers between patients with T2DM and controls, to identify key genes associated with T2DM pathogenesis, and to predict the underlying molecular mechanisms. As a result, a total of 1,512 differentially expressed (DE) lncRNAs and 1,923 DE mRNAs were identified through microarray analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that multiple metabolic processes were dysregulated such as small molecule, organic acid, lipid, and branched chain amino acid metabolism. Protein-protein interaction network was constructed, and 10 hub mRNAs were identified, including EHHADH, ATM, ACOX1, PIK3R1, EGFR, UQCRFS1, HMGCL, UQCRC2, NDUFS3, and F2. RT-qPCR was conducted to verify the validity of microarray results. Then, coding-noncoding co-expression network and competing endogenous RNA (ceRNA) network were analyzed to predict the lncRNA-mRNA and lncRNA-miRNA-mRNA regulatory patterns. Subsequently, 10 key intermediating miRNAs in ceRNA networks with a node degree >80 were identified, including hsa-miR-5692a, hsa-miR-12136, hsa-miR-5680, hsa-miR-1305, hsa-miR-6833-5p, hsa-miR-7159-5p, hsa-miR-548as-3p, hsa-miR-6873-3p, hsa-miR-1290, and hsa-miR-4768-5p. In conclusion, this study evaluated the transcriptome profiling of lncRNAs and mRNAs in livers from patients with T2DM, with a value for understanding the molecular mechanism of disease pathogenesis and identifying effective biomarkers in clinical diagnosis.
Prevalence of Fabry Disease among Patients with Parkinson’s Disease
Authors: Lackova Alexandra , Beetz Christian , Oppermann Sebastian , Bauer Peter , Pavelekova Petra , Lorincova Tatiana , Ostrozovicova Miriam , Kulcsarova Kristina , Cobejova Jana , Cobej Martin , Levicka Petra , Liesenerova Simona , Sendekova Daniela , Sukovska Viktoria , Gdovinova Zuzana , Han Vladimir , Rizig Mie , Houlden Henry , Skorvanek Matej
Published: January 2022

Background. An increased prevalence of Parkinson’s disease (PD) disease has been previously reported in subjects with Fabry disease (FD) carrying alpha-galactosidase (GLA) mutations and their first-line relatives. Moreover, decreased alpha-galactosidase A (AGLA) enzymatic activity has been reported among cases with PD compared to controls. Objective. The aim of our study was to determine the prevalence of FD among patients with PD. Methods. We recruited 236 consecutive patients with PD from February 2018 to December 2020. Clinical and sociodemographic data, including the MDS-UPDRS-III scores and HY stage (the Hoehn and Yahr scale), were collected, and in-depth phenotyping was performed in subjects with identified GLA variants. A multistep approach, including standard determination of AGLA activity and LysoGb3 in males, and next-generation based GLA sequencing in all females and males with abnormal AGLA levels was performed in a routine diagnostic setting. Results. The mean age of our patients was 68.9 ± 8.9 years, 130 were men (55.1%), and the mean disease duration was 7.77 ± 5.35 years. Among 130 men, AGLA levels were low in 20 patients (15%), and subsequent Lyso-Gb3 testing showed values within the reference range for all tested subjects. In 126 subsequently genetically tested patients, four heterozygous p.(Asp313Tyr) GLA variants (3.2%, MAF 0.016) were identified; all were females. None of the 4 GLA variant carriers identified had any clinical manifestation suggestive of FD. Conclusions. The results of this study suggest a possible relationship between FD and PD in a small proportion of cases. Nevertheless, the GLA variant found in our cohort is classified as a variant of unknown significance. Therefore, its pathogenic causative role in the context of PD needs further elucidation, and these findings should be interpreted with caution.
Cruciate Substituting Implants in Primary Total Knee Arthroplasty
Authors: Volkmar Alexander J. , Elrod Robert , Vickery Justin W. , Yang Charlie C. , Polkowski Gregory G. , Martin J. Ryan
Published: January 2022

The use of cruciate substituting (CS) total knee replacement has been increasing in popularity. There are numerous factors that have likely contributed to this expansion. The CS philosophy incorporates the ease of use commonly cited by advocates of the posterior stabilized (PS) total knee design with the bone preservation associated with a cruciate retaining (CR) design. The ultra-congruent highly cross-linked polyethylene liner increases stability without an appreciable change in wear. Furthermore, balancing the flexion and extension gaps does not require “titrating” the posterior cruciate ligament, improving the user-friendliness. This paper reviews the nuances of this implant design compared to PS and CR designs as well as provides surgical technique recommendations/considerations.