bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of insertion sequence elements in plasmids relating to mgrB gene disruption causing colistin resistance in Klebsiella pneumoniae
Authors: Fordham Stephen Mark Edward , Mantzouratou Anna , Sheridan Elizabeth
Published: January 2022

Colistin is a last resort antibiotic for the treatment of carbapenemase producing Klebsiella pneumoniae. The disruption of the mgrB gene by insertion sequences (ISs) is a mechanism mediating colistin resistance. Plasmids encode mobilizable IS elements which integrate into the mgrB gene in K. pneumoniae causing gene inactivation and colistin resistance. The species prevalence of mgrB‐gene disrupting insertion elements ISL3 (ISKpn25), IS5 (ISKpn26), ISKpn14, and IS903B present on plasmids were assessed. IS containing plasmids were also scanned for antimicrobial resistance genes, including carbapenem resistant genes. Plasmids encoding ISs are abundant in K. pneumoniae. IS903B was found in 28 unique Inc groups, while ISKpn25 was largely carried by IncFIB(pQil) plasmids. ISKpn26 and ISKpn14 were most often found associated with IncFII(pHN7A8) plasmids. Of the 34 unique countries which contained any of the IS elements, ISKpn25 was identified from 26. ISKpn26, ISKpn14, and IS903B ISs were identified from 89.3%, 44.9%, and 23.9% plasmid samples from China. Plasmids carrying ISKpn25, ISKpn14, and ISKpn26 IS have a 4.6‐, 6.0‐, and 6.6‐fold higher carbapenemase gene count, respectively, relative to IS903B‐carrying plasmids. IS903B bearing plasmids have a 20‐, 5‐, and 5‐fold higher environmental source isolation count relative to ISKpn25, ISKpn14, and ISKpn26 bearing plasmids. ISKpn25 present on IncFIB(pQil) sourced from clinical settings is established across multiple countries, while ISKpn26, ISKpn14, and IS903B appear most often in China. Carbapenemase presence in tandem with IS elements may help promote an extensively drug resistant profile in K. pneumoniae limiting already narrow treatment options.
Memory‐type boundary stabilization of a transmission problem for Kirchhoff wave equations
Authors: Fan Sheng , Feng Baowei
Published: January 2022

In this paper, we consider a transmission problem for Kirchhoff‐type wave equations with boundary condition determined by the long‐range memory. The wave propagation over bodies consisting of two physically different types of materials. One component is clamped, and the other is in a viscoelastic fluid producing a dissipative mechanism on the boundary. Under a wider assumption of the kernel, we establish a more general decay rate of energy, which improves earlier results established in the literature.
Changes in median eminence of fatty acid–binding protein 3 in a mouse model of pain
Authors: Tachibana Dan , Nakamoto Kazuo , Tokuyama Shogo
Published: January 2022

Aims

Fatty acid–binding protein (FABP) regulates polyunsaturated fatty acid (PUFA) intracellular trafficking and signal transduction. Our previous studies demonstrated that the alteration of PUFA in the hypothalamus is involved in pain process. However, how FABP subtypes change during pain remain unclear. Here, we examined the expression changes and localization in the hypothalamic FABP subtype in postoperative pain model mice.

Methods

Paw incision–induced postoperative methods were adopted as a pain model in male ddY mice. Mechanical allodynia was examined using the von Frey test. The analysis of several FABPs mRNA was measured by real‐time PCR, and cellular localization of its protein level was measured by immunofluorescent study.

Results

Postoperative pain mouse elicited mechanical allodynia on Day 2 after paw incision, and mRNA expression of FABP3 increased significantly in the hypothalamus in the postoperative pain mouse model compared to that in control mice. FABP3 protein expressed in the median eminence and the arcuate nucleus, and colocalized with Iba‐1, which is a microglial cell marker. Its protein level significantly increased in the median eminence on Day 2 after incision and returned to the control level on Day 4 after incision.

Conclusions

Our findings indicate that FABP3 in the median eminence may change in pain stimuli and may represent a molecular link controlling pain.
Association between idiopathic pulmonary hemosiderosis and celiac disease in pediatric patients: A scoping review of the literature over the past 50 years
Authors: Saha Biplab K , Saha Santu , Bonnier Alyssa , Saha Baidya Nath
Published: January 2022

Introduction

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of diffuse alveolar hemorrhage, the mechanism of which is currently unknown. Nearly one‐third of pediatric patients with IPH test positive for Celiac disease (CD) serology. Several hypothetical mechanisms have been proposed to unify the coexistence of these two entities, also referred to as Lane‐Hamilton syndrome (LHS).

Method

This manuscript is a scoping review of the medical literature. Medline, Embase, and PubMed Central databases were searched between 1971 and 2021 with appropriate search words to identify all cases of pediatric LHS.

Results

A total of 20 manuscripts with 23 pediatric patients with LHS were identified. The mean age was 11 years, and 13/23 (56.5%) of the children were boys. Hemoptysis was present in 57% of patients during diagnosis. Bronchoscopy with bronchoalveolar lavage demonstrating hemosiderin laden macrophages was the primary mode of diagnostic confirmation. Only three patients underwent lung biopsy. Any significant GI symptom was reported in a minority of patients (22%). Iron deficiency anemia on presentation was described in 83% of children. The majority of patients were malnourished. Serology for CD was positive in all patients, as was the histopathologic analysis of the small bowel biopsy. No patients had any other autoantibody positivity. The introduction of gluten free diet (GFD) was associated with a positive response in 20/23 patients.

Conclusion

All pediatric patients with IPH should undergo screening for CD. Low serum ferritin in patients with IPH could be suggestive of coexisting CD. Strict GFD should be tried as the initial therapy.
Chlorothalonil alters the gut microbiota and reduces the survival of immature honey bees reared in vitro
Authors: Wu Tong , Han Bo , Wang Xing , Tong Yuemin , Liu Feng , Diao Qingyun , Dai Pingli
Published: January 2022

BACKGROUND

Chlorothalonil is a nonsystemic fungicide, and it is one of the most widely detected pesticides in bee hives. The effect of chlorothalonil on the survival, weight, and gut microbiota of immature Apis mellifera L. reared in vitro was studied.

RESULTS

Larvae were fed 1, 2, 4, 8, and 16 μg/mL chlorothalonil and compared with larvae fed the negative control (diet without any additives), positive control (45 mg/L dimethoate), and solvent control (2% acetone). Compared with the control groups, the survival of the 2, 4, 8, and 16 μg/mL chlorothalonil treatments was significantly reduced. The no‐observed‐adverse‐effect concentration of chlorothalonil was 1 μg/mL. Chlorothalonil had no significant effect on larval weight. The gut bacterial community composition of newly emerged bees was determined by PacBio 16S rDNA gene sequencing. linear discriminant analysis effect size (LEFSe) analysis showed that Pseudomonadales and Burkholderiales were affected by exposure to chlorothalonil.

CONCLUSION

Chlorothalonil reduced the survival of honey bee larvae and altered the gut microbiota of newly emerged bees. The risk of pesticides to honey bees is related to their toxicity and exposure dose.
Health‐promoting and disease‐mitigating potential of Verbascum thapsus L. (common mullein): A review
Authors: Gupta Ashutosh , Atkinson Alexa N. , Pandey Abhay Kumar , Bishayee Anupam
Published: January 2022

Medicinal plants represent rich sources of traditional medicines and numerous currently used medicines are either directly or indirectly derived from plants. Verbascum thapsus L. (great mullein or common mullein), a medicinal herb indigenous to northern Africa, western and central Asia, and Europe, has been brought to the Americas and Australia. It has been used as a medicine for lung, skin and throat disorders and has a long history of therapeutic importance, particularly as an astringent and calming agent. Presently, the dried leaves, flowers, various plant extracts and flower oil are used in several formulations within Indian traditional medicine. An extract taken from the roots is useful in minimizing toothache, and it also relieves stiffness and seizures. V. thapsus contains a wide variety of phytoconstituents, such as flavonoids, iridoid, phenylethanoid and phenylpropanoid glycosides, saponins, as well as vitamin C and minerals. The most valuable constituents are coumarin and hesperidin, which possess healing properties. Emerging literature based on experimental studies on V. thapsus demonstrates various biological and pharmacological properties, including antiviral, antioxidant, analgesic, sedative, anti‐inflammatory, hypnotic, antibacterial, antifungal, as well as anticancer activities. The present review provides an updated, comprehensive, and critical evaluation of various health‐promoting and disease‐mitigating properties of V. thapsus.
Resonant Oscillations of Josephson Current in Nb‐Bi2Te2.3Se0.7‐Nb Junctions
Authors: Stolyarov Vasily S. , Roditchev Dimitri , Gurtovoi Vladimir L. , Kozlov Sergey N. , Yakovlev Dmitriy S. , Skryabina Olga V. , Vinokur Valerii M. , Golubov Alexander A.
Published: January 2022

Josephson proximity junctions and devices employing topological insulators are promising candidates for realizing topological superconductivity and topologically protected quantum circuits. Here, the new type of oscillations of the critical Josephson current in the ballistic Nb‐Bi2Te2.3Se0.7‐Nb junctions subject to the magnetic fields is reported. The oscillations appear below ≈400 mK and have a very unusual sharp‐peaked shape. Their ultra‐short period ≈1 Oe, by orders of magnitude shorter than the expected periodicity due to fluxoid quantization in the device, corresponds to the extremely low energy scale ≈1 eV. It is established that the observed effect is due to the resonant transmission of Andreev quasiparticles via the peculiar energy levels forming near the S‐TI interfaces.
Anti‐unwinding adaptive spacecraft attitude tracking control based on similar skew‐symmetric structures
Authors: Su Yunzhe , Yang Yajun , Yang Xuerong , Zhang Xueyang
Published: January 2022

This article addresses the adaptive attitude tracking control based on similar skew‐symmetric structure. Based on the structure, a novel adaptive backstepping scheme is proposed to design the attitude controller. To avoid unwinding, a rotation matrix rather than a quaternion is used to describe the attitude. Correspondingly, the application of similar skew‐symmetric structure is extended from euclidean space to noneuclidean space, for which the stability is proved by combining the Lyapunov function and the Morse–Lyapunov function. In addition, the smooth projection function is adopted to design the adaptive law for the unknown parameters. And the input‐to‐state stable property of the closed‐loop system is proved when considering the unmodeled disturbance. Finally, numerical simulations are carried out to illustrate the effectiveness of the proposed controllers.
Anti‐disturbance resilient tracking control for semi‐Markov jumping systems
Authors: Priyanka Sargunan , Sakthivel Rathinasamy , Kwon Ohmin , Mohanapriya Saminathan
Published: January 2022

This article investigates the output tracking problem of semi‐Markov jump systems with exogenous disturbance and generally uncertain transition probability rates. In particular, the elements in the transition rates are allowed to be known, uncertain or completely unknown. In specific, a state‐space of the modified repetitive controller is considered for tracking the given reference signals. Then, a generalized extended state observer is constructed to estimate the external disturbances and these estimates are incorporated in the control law to reject the disturbances effectively. Moreover, additive gain fluctuations are considered in the control design to tolerate gain fluctuations. First, a continuous‐discrete two‐dimensional (2D) delayed system is developed based on the lifting technique to characterize the repetitive control system's control and learning behavior. Then a sufficient condition for the bounded stability of the 2D hybrid system is obtained by choosing a suitable Lyapunov–Krasovskii functional. In addition, the control and observer gains are evaluated by solving a set of linear matrix inequalities and using the pole placement technique. At last, a robot arm model is presented to show the applicability of the proposed control scheme and a comparison study is made over some existing literature.
Photo‐Activated Nanofibrous Membrane with Self‐Rechargeable Antibacterial Function for Stubborn Infected Cutaneous Regeneration
Authors: Yang Yingming , Zhou Xiong , Chan Yau Kei , Wang Ziyou , Li Limei , Li Jiyao , Liang Kunneng , Deng Yi
Published: January 2022

For quick disinfection treatment, phototherapy, including photothermal therapy and photodynamic therapy, has emerged as a promising alternative to conventional methods. However, the bactericidal effect of phototherapy, which only works upon light, is short‐lived. The remaining bacteria in situ may repopulate when the irradiation of light is withdrawn. To address this refractory concern, an antibacterial fibrous membrane consisting of electrospun poly (polycaprolactone) scaffolds and polydopamine (pDA) coated MXene/Ag3PO4 bioheterojunctions (MX@AgP bio‐HJs) is devised and developed. Upon near‐infrared (NIR) illumination, the MX@AgP nanoparticle (NP) in nanofibrous electrospun membranes exert the excellent bactericidal effect of phototherapy and release Ag+ ions which stop the remaining bacteria from multiplying in the dark state. When removing NIR light, pDA in situ reduces Ag+ ions to Ag0 NPs to realize the self‐rechargeability of Ag+ ions and provides enough Ag+ ions for the second phototherapy. In vivo results show that photoactivated nanofibrous membranes can re‐shape an infected wound microenvironment to the regenerative microenvironment through killing bacteria, ceasing bleeding, increasing epithelialization, and collagen deposition on the wound bed, as well as promoting angiogenesis. As predicted, the proposal work offers potential prospects for nanofibrous membranes with NIR‐assisted “self‐rechargeable” antibacterial properties to treat bacteria‐infected full‐thickness wounds.
Bandgap Engineering in 2D Lateral Heterostructures of Transition Metal Dichalcogenides via Controlled Alloying
Authors: Nugera Florence A. , Sahoo Prasana K. , Xin Yan , Ambardar Sharad , Voronine Dmitri V. , Kim Un Jeong , Han Yoojoong , Son Hyungbin , Gutiérrez Humberto R.
Published: January 2022

2D heterostructures made of transition metal dichalcogenides (TMD) have emerged as potential building blocks for new‐generation 2D electronics due to their interesting physical properties at the interfaces. The bandgap, work function, and optical constants are composition dependent, and the spectrum of applications can be expanded by producing alloy‐based heterostructures. Herein, the successful synthesis of monolayer and bilayer lateral heterostructures, based on ternary alloys of MoS2(1−x)Se2x–WS2(1−x)Se2x, is reported by modifying the ratio of the source precursors; the bandgaps of both materials in the heterostructure are continuously tuned in the entire range of chalcogen compositions. Raman and photoluminescence (PL) spatial maps show good intradomain composition homogeneity. Kelvin probe measurements in different heterostructures reveal composition‐dependent band alignments, which can further be affected by unintentional electronic doping during the growth. The fabrication of sequential multijunction lateral heterostructures with three layers of thickness, composed of quaternary and ternary alloys, is also reported. These results greatly expand the available tools kit for optoelectronic applications in the 2D realm.
Standards‐based modeling and deployment of serverless function orchestrations using BPMN and TOSCA
Authors: Yussupov Vladimir , Soldani Jacopo , Breitenbücher Uwe , Leymann Frank
Published: January 2022

Function‐as‐a‐Service (FaaS) is a cloud service model enabling to implement serverless applications for a variety of use cases. These range from scheduled calls of single functions to complex function orchestrations executed using orchestration services such as AWS step functions. However, since the available function orchestration technologies vary in functionalities, supported modeling languages, and APIs, modeling such function orchestrations and their deployment require significant technology‐specific expertise. Moreover, the resulting models are typically not portable due to provider‐ and technology‐specific details, and major efforts are required when exchanging an orchestrator or provider due to such lock‐ins. To tackle this issue, we introduce a vendor‐ and technology‐agnostic method for the modeling and deployment of serverless function orchestrations, which relies on the business process model and notation (BPMN) and topology and orchestration specification for cloud applications (TOSCA) standards for modeling function orchestrations and their deployment, respectively. We also present a toolchain for modeling serverless function orchestrations in BPMN, generating proprietary models supported by different function orchestration technologies from BPMN models, specifying their actual deployment in TOSCA, and then enacting such deployment. Finally, we illustrate a case study applying our method and toolchain in practice.
Effect of web stiffeners on lateral buckling of I‐section simply supported beam
Authors: Bui Hung Cuong , Trinh Duy Khanh , Nguyen Minh Tuyen
Published: January 2022

Vertical web stiffeners partially restrain the warping of the simply supported beam when lateral buckling occurs. The restraint increases the critical moment of the beam. This increase can be shown through the decrease of the warping effective length factor in the general formula determining the critical moment. An approximative expression to determine the warping effective length factor is proposed and verified by numerical analysis. Simply supported beams stiffened by vertical stiffeners, including end plates, which are subjected respectively to uniform bending, uniformly distributed loads, two concentrated loads and one concentrated load are numerically analyzed using COMSOL finite element software. The reliability of the proposed expression is assured by small coefficients of variation and very high coefficients of determination. It can provide a solution to improve the critical moment in the design of the beam without using an intermediate lateral bracing system.
Bending response of sandwich panels with steel skins and aluminium foam core
Authors: Latour Massimo , D'Aniello Mario , Babcsan Norbert , Capone Paolo , Landolfo Raffaele , Rizzano Gianvittorio
Published: January 2022

Nominated for Eurosteel 2021 Best Paper Award

The introduction to the market of metal foams represents a significant opportunity to increase the use of metal in the construction market. In fact, the development of new products made of metal foams and steel could improve the performance of conventional buildings in terms of stiffness and resistance. The first structural applications of these materials have already shown the potential of composites made of foam and steel, and demonstrated the feasibility of producing mono‐dimensional and bi‐dimensional elements with a high resistance‐to‐weight ratio. Reducing the structural weight can be a significant advantage in many cases, such as infrastructures or buildings in seismic zones. Within this framework, the work presented in this paper aims to assess the response of composite sandwich panels made of steel and aluminium foam using a set of tests that will serve as the basis for developing a new system of dry‐assembled composite floors. The tests were carried out at the Strength laboratory (Structural Engineering Test Hall) at the University of Salerno, Italy and were designed to verify the mechanical properties of metal foam panels and double‐skin glued sandwich panels. The tests have shed light on the basic mechanical properties of both foams and sandwich panels.
Collider signatures of vector-like fermions from a flavor symmetric model
Authors: Bonilla Cesar , Hernández A. E. Cárcamo , Gonçalves João , Freitas Felipe F. , Morais António P. , Pasechnik R.
Published: January 2022

Abstract

We propose a model with two Higgs doublets and several SU(2) scalar singlets with a global non-Abelian flavor symmetry $$ {\mathcal{Q}}_6\times {\mathcal{Z}}_2 $$

Q
6

×

Z
2

. This discrete group accounts for the observed pattern of fermion masses and mixing angles after spontaneous symmetry breaking. In this scenario only the third generation of fermions get their masses as in the Standard Model (SM). The masses of the remaining fermions are generated through a seesaw-like mechanism. To that end, the matter content of the model is enlarged by introducing electrically charged vector-like fermions (VLFs), right handed Majorana neutrinos and several SM scalar singlets. Here we study the processes involving VLFs that are within the reach of the Large Hadron Collider (LHC). We perform collider studies for vector-like leptons (VLLs) and vector-like quarks (VLQs), focusing on double production channels for both cases, while for VLLs single production topologies are also included. Utilizing genetic algorithms for neural network optimization, we determine the statistical significance for a hypothetical discovery at future LHC runs. In particular, we show that we can not safely exclude VLLs for masses greater than 200 GeV. For VLQ’s in our model, we show that we can probe their masses up to 3.8 TeV, if we take only into account the high-luminosity phase of the LHC. Considering Run-III luminosities, we can also exclude VLQs for masses up to 3.4 TeV. We also show how the model with predicted VLL masses accommodates the muon anomalous magnetic moment.
Real-space RG, error correction and Petz map
Authors: Furuya Keiichiro , Lashkari Nima , Ouseph Shoy
Published: January 2022

Abstract

There are two parts to this work: first, we study the error correction properties of the real-space renormalization group (RG). The long-distance operators are the (approximately) correctable operators encoded in the physical algebra of short-distance operators. This is closely related to modeling the holographic map as a quantum error correction code. As opposed to holography, the real-space RG of a many-body quantum system does not have the complementary recovery property. We discuss the role of large N and a large gap in the spectrum of operators in the emergence of complementary recovery.

Second, we study the operator algebra exact quantum error correction for any von Neumann algebra. We show that similar to the finite dimensional case, for any error map in between von Neumann algebras the Petz dual of the error map is a recovery map if the inclusion of the correctable subalgebra of operators has finite index.
In-process feedback control of tube hydro-forming process
Authors: Endelt Benny
Published: January 2022

The present work will address the problem of designing an in-process control system for a tube hydro-forming process, controlling the tool filling forming a T-tube. The control problem is nontrivial as wrinkling and bursting will develop rapidly and, in most cases, are irreversible—thus, the control system must react fast and without extensive overshoot. The objective is to control the tool filling, reproducing a reference filling trajectory, where the controller input is defined as a correction of the reference forming pressure. The control system was verified experimentally, using four different error scenarios. Initially, the error was provoked, by manipulating the input signal, and for all three cases, the control system successfully eliminates both wrinkling and bursting. Finally, the material was changed going from an aluminum grade 5049-0 to 6060-T6 also; in this case, the control system eliminates the error and stabilizes the process. The control strategy and implementation was developed using numerical simulation (explicit finite element), and the controller implementation was reused directly in the experimental setup without manipulating or scaling the gain factors.
Design and validation of a sheet metal clamping system for additive manufacturing and post-processing
Authors: Ferchow Julian , Bühler Marvin , Schlüssel Marcel , Zumofen Livia , Klahn Christoph , Hofmann Urs , Kirchheim Andreas , Meboldt Mirko
Published: January 2022

Automated clamping for post-processing of mass-customized parts is a challenging step in the laser powder bed fusion (LPBF) process chain. In this study, a novel modular sheet metal clamping system was developed that uses disposable sheet metal profiles as a universal interface for the LPBF, robotic handling, and milling processes. Based on a fundamental investigation of hybrid additive manufacturing, the sheet metal clamping system was designed to use the same interface for the LPBF and milling processes. Subsequent an end-to-end validation was performed for the entire process chain. The concept of the sheet metal clamping system gives milling tools access to a part on five to six sides. Further, the part can be accessed from the top and bottom sides, and simplifying the removal of LPBF supports. No clamping forces are induced in the LPBF part, which is especially important for filigree structures. The sheet metal clamping system’s underlying concept could be adapted to automating the LPBF process chain for applications such as prosthetic dentistry.
Updated Austrian treatment algorithm in HER2+ metastatic breast cancer
Authors: Bartsch Rupert , Gampenrieder Simon Peter , Rinnerthaler Gabriel , Petru Edgar , Egle Daniel , Petzer Andreas , Balic Marija , Pluschnig Ursula , Sliwa Thamer , Singer Christian
Published: January 2022

A group of Austrian breast cancer specialists met in December 2020 to establish a comprehensive clinical benefit-risk profile of available HER2-targeted therapies based on recent data and to develop an updated treatment algorithm by consensus over several months in 2021. A total of four scenarios were developed in which treatment strategies appropriate for specific patient profiles were evaluated. Consensus was established by detailed discussions of each scenario and by reaching full consensus.
An analytical study of participating policies with minimum rate guarantee and surrender option
Authors: Chiarolla Maria B. , De Angelis Tiziano , Stabile Gabriele
Published: January 2022

We perform a detailed theoretical study of the value of a class of participating policies with four key features: (i) the policyholder is guaranteed a minimum interest rate on the policy reserve; (ii) the contract can be terminated by the holder at any time until maturity (surrender option); (iii) at the maturity (or upon surrender), a bonus is credited to the holder if the portfolio backing the policy outperforms the current policy reserve; (iv) due to solvency requirements, the contract ends if the value of the underlying portfolio of assets falls below the policy reserve.

Our analysis is probabilistic and relies on optimal stopping and free boundary theory. We find a structure of the optimal surrender strategy which was undetected by previous (mostly numerical) studies on the topic. Optimal surrender of the contract is triggered by two ‘stop-loss’ boundaries and by a ‘too-good-to-persist’ boundary (in the language of Ekström and Vaicenavicius in Stoch. Process. Appl. 130: 806–823, 2020). Financial implications of this strategy are discussed in detail and supported by extensive numerical experiments.
Flavopiridol Mitigates the Progression of Monocrotaline-Induced Pulmonary Hypertension in Rats by Targeting Cyclin-Dependent Kinase 9
Authors: Jia Qi , Hu Zhiqiang , Song Nannan , Mao Weike
Published: January 2022

Purpose

To investigate the role of cyclin-dependent kinase 9 (CDK9) and the therapeutic potential of a CDK9 inhibitor (flavopiridol) in monocrotaline (MCT)-induced pulmonary hypertension (PH).

Methods

For the in vivo experiments, rats with PH were established by a single intraperitoneal injection of MCT (60 mg/kg). After 2 weeks of MCT injection, rats were then treated with flavopiridol (5 mg/kg, i.p., twice a week) or vehicle for 2 weeks. For the in vitro experiments, human pulmonary artery smooth muscle cells (HPASMCs) were treated with flavopiridol (0.025-1 μM) or vehicle under hypoxic conditions. Hemodynamic recording, right ventricle histology, lung histology, and pulmonary arterial tissue isolation were performed. The expression levels of CDK9, RNA polymerase II, c-Myc, Mcl-1, and survivin were determined by qRT-PCR and western blotting, and the proliferation and apoptosis of rat pulmonary arterial tissues and/or HPASMCs were also assayed.

Results

Compared to the control group, CDK9 was upregulated in pulmonary arterial tissues from MCT-induced PH rats and hypoxic cultured HPASMCs. Upregulation of CDK9 was associated with enhanced phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNA pol II) at serine-2 (Ser-2), promoting the expression of prosurvival and antiapoptotic proteins (c-Myc, Mcl-1, and survivin). Furthermore, treatment with flavopiridol (5 mg/kg) significantly alleviated pulmonary artery remodeling and partially reversed the progression of MCT-induced PH. Consistently, flavopiridol (0.5 μM) treatment decreased the proliferation and induced the apoptosis of cultured HPASMCs under hypoxic conditions. As a result of CDK9 inhibition and subsequent inhibition of RNA pol II CTD phosphorylation at Ser-2, flavopiridol decreased c-Myc, Mcl-1, and survivin expression in isolated pulmonary small arteries, leading to cell growth inhibition and apoptosis.

Conclusion

Flavopiridol mitigates the progression of MCT-induced PH in rats by targeting CDK9.
Parent Management Training Combined with Group-CBT Compared to Parent Management Training Only for Oppositional Defiant Disorder Symptoms: 2-Year Follow-Up of a Randomized Controlled Trial
Authors: Helander Maria , Enebrink Pia , Hellner Clara , Ahlen Johan
Published: January 2022

Parent management training (PMT) is recommended treatment for children with oppositional defiant disorder (ODD) and child-directed cognitive behavior therapy (CBT) is also recommended for school-aged children. The current study examined 2-year follow-up effects of parent management training (PMT) combined with the CBT based group intervention Coping Power Program (CPP) compared to PMT only. Results showed long-term effectiveness of both PMT and PMT combined with CPP in reduced disruptive behavior problems and harsh parenting strategies, and increased emotion regulation- and social communication skills. The earlier reported increase in emotion regulation- and social communication skills in the PMT with CPP condition during treatment remained stable while the PMT condition showed continued improvement during the follow-up period. To conclude, PMT with CPP did generally not provide significant benefits at the 2-year follow-up compared to PMT, apart from an improvement earlier in time regarding emotion regulation- and social communication skills.

Trial registration number ISRCTN10834473, date of registration: 23/12/2015.
Role of glycosyltransferases in carcinogenesis; growth factor signaling and EMT/MET programs
Authors: Takahashi Motoko , Hasegawa Yoshihiro , Maeda Kento , Kitano Masato , Taniguchi Naoyuki
Published: January 2022

The glycosylation of cell surface receptors has been shown to regulate each step of signal transduction, including receptor trafficking to the cell surface, ligand binding, dimerization, phosphorylation, and endocytosis. In this review we focus on the role of glycosyltransferases that are involved in the modification of N-glycans, such as the effect of branching and elongation in signaling by various cell surface receptors. In addition, the role of those enzymes in the EMT/MET programs, as related to differentiation and cancer development, progress and therapy resistance is discussed.
Exploring the Effect of Augmented Reality on Cognitive Load, Attitude, Spatial Ability, and Stereochemical Perception
Authors: Elford Daniel , Lancaster Simon J. , Jones Garth A.
Published: January 2022

Augmented reality (AR) has the capacity to afford a virtual experience that obviates the reliance on using two-dimensional representations of 3D molecules for teaching stereochemistry to undergraduate students. Using a combination of quantitative instruments and qualitative surveys/interviews, this study explored the relationships between students’ attitudes, perceived cognitive load, spatial ability, and academic performance when engaging in an asynchronous online stereochemistry activity. Our activity was designed using elements of game-based learning, and integrated AR technologies. The control group was provided with a copy of our activity that used two-dimensional drawings, whereas the AR group completed an activity using the AR technologies. For this cohort of students, results indicated significant improvement in academic performance in both the control and AR groups. The introduction of AR technologies did not result in the AR group outperforming the control group. Participants from both groups displayed significant improvements in spatial ability throughout the research period. Further, a moderate correlation (rs = 0.416) between students’ spatial ability and academic performance was found. No significant intergroup differences in the perceived cognitive loads of students were observed. A significant difference was observed on one item of the Intellectual Accessibility subscale of the ASCI (V2), Complicated–Simple. We found no correlation for student attitude or cognitive load with academic performance. The findings of this study provide insights for future AR-related studies to explore the role of spatial ability, student attitude, and cognitive load in learning performance.
Generalized vec trick for fast learning of pairwise kernel models
Authors: Viljanen Markus , Airola Antti , Pahikkala Tapio
Published: January 2022

Pairwise learning corresponds to the supervised learning setting where the goal is to make predictions for pairs of objects. Prominent applications include predicting drug-target or protein-protein interactions, or customer-product preferences. In this work, we present a comprehensive review of pairwise kernels, that have been proposed for incorporating prior knowledge about the relationship between the objects. Specifically, we consider the standard, symmetric and anti-symmetric Kronecker product kernels, metric-learning, Cartesian, ranking, as well as linear, polynomial and Gaussian kernels. Recently, a$$O(nm+nq)$$O(nm+nq)time generalized vec trick algorithm, where$$n$$n,$$m$$m, and$$q$$qdenote the number of pairs, drugs and targets, was introduced for training kernel methods with the Kronecker product kernel. This was a significant improvement over previous$$O(n^2)$$O(n2)training methods, since in most real-world applications$$m,q<< n$$m,q<<n. In this work we show how all the reviewed kernels can be expressed as sums of Kronecker products, allowing the use of generalized vec trick for speeding up their computation. In the experiments, we demonstrate how the introduced approach allows scaling pairwise kernels to much larger data sets than previously feasible, and provide an extensive comparison of the kernels on a number of biological interaction prediction tasks.
Mitigation of False Brinelling in a Roller Bearing: A Case Study of Four Types of Greases
Authors: Lin Chih-Ling , Fallahnezhad Khosro , Brinji Osama , Meehan Paul A.
Published: January 2022

Four commercial greases with various thickeners and base oils were experimentally examined to compare their false brinelling wear resistance in a test rig simulating roller bearings during rail/sea transportation for the first time. Greases containing zinc dialkyl dithiophosphates (ZDDP) showed superior false brinelling reduction, evidenced by no visible wear mark in the raceways. The mechanism for false brinelling mitigation was shown to be from a ZDDP-induced tribofilm which decreases the friction and wear coefficient in the contact area. Surface chemical analysis showed that for grease lubricated fretting contacts, ZDDP-derived tribofilms can be generated in the presence of micro-sliding motions and energy dissipation at the contact interface at low frequency (i.e., 4–8 Hz), due to the mechanochemical reactions. For greases without ZDDP, false brinelling wear was reduced by 97% when using grease with a more abundant and less viscous oil, which bleeds readily from an open structured thickener. The results highlight the ability of ZDDP as an additive in grease to better protect roller bearings against false brinelling during rail/sea transportation.
Explainable depression detection with multi-aspect features using a hybrid deep learning model on social media
Authors: Zogan Hamad , Razzak Imran , Wang Xianzhi , Jameel Shoaib , Xu Guandong
Published: January 2022

The ability to explain why the model produced results in such a way is an important problem, especially in the medical domain. Model explainability is important for building trust by providing insight into the model prediction. However, most existing machine learning methods provide no explainability, which is worrying. For instance, in the task of automatic depression prediction, most machine learning models lead to predictions that are obscure to humans. In this work, we propose explainable Multi-Aspect Depression Detection with Hierarchical Attention Network MDHAN, for automatic detection of depressed users on social media and explain the model prediction. We have considered user posts augmented with additional features from Twitter. Specifically, we encode user posts using two levels of attention mechanisms applied at the tweet-level and word-level, calculate each tweet and words’ importance, and capture semantic sequence features from the user timelines (posts). Our hierarchical attention model is developed in such a way that it can capture patterns that leads to explainable results. Our experiments show that MDHAN outperforms several popular and robust baseline methods, demonstrating the effectiveness of combining deep learning with multi-aspect features. We also show that our model helps improve predictive performance when detecting depression in users who are posting messages publicly on social media. MDHAN achieves excellent performance and ensures adequate evidence to explain the prediction.
How Has Access to Care for Medi-Cal Enrollees Fared Relative to Employer-Sponsored Insurance 4 Years After the Affordable Care Act Expansion?
Authors: Babey Susan H. , Ponce Ninez A. , Becker Tara , Rasmussen Petra W. , Scheitler A. J.
Published: January 2022

Background

The number of Californians covered by Medi-Cal increased more than 50% between 2013 and 2018, largely due to expansion under the Affordable Care Act (ACA). This rapid expansion of Medicaid rolls prompted concerns that Medi-Cal enrollees would face greater difficulty accessing health care.

Objective

Examine whether gaps in access to care between Medi-Cal and employer-sponsored insurance (ESI) present in 2013 (prior to ACA implementation) had changed by 2018 (several years post implementation).

Design

Secondary analysis of data from the 2013 and 2018 California Health Interview Survey. The sample included adults of ages 18–64 insured all year and covered by ESI or Medi-Cal at time of interview. Logistic regressions were used to examine variation across years in the association between access to care and insurance type.

Main Measures

Five access to care outcomes were assessed: no usual source of care, not accepted as new patient in past year, insurance not accepted in past year, delayed medical care in past year, and difficulty getting timely appointment. The main predictors of interest were type of insurance (Medi-Cal or ESI) and survey year (2013 or 2018).

Key Results

The association between insurance type and access to care changed significantly over time for three outcomes: not accepted as new patient in past year (OR = 0.55, 95% CI = 0.32–0.97), delayed medical care in past year (OR = 1.55, 95% CI = 1.06–2.25), and difficulty getting timely appointment (OR = 0.41, 95% CI = 0.23–0.74). Predicted probabilities indicate gaps between Medi-Cal and ESI narrowed for not accepted as new patient in past year and difficulty getting timely appointment, but widened for delayed medical care.

Conclusions

Despite the rapid expansion in the number of Californians covered by Medi-Cal, most gaps in access to care between Medi-Cal and ESI enrollees improved or did not significantly change between 2013 and 2018.
HGF Secreted by Mesenchymal Stromal Cells Promotes Primordial Follicle Activation by Increasing the Activity of the PI3K-AKT Signaling Pathway
Authors: Mi Xin , Jiao Wenlin , Yang Yajuan , Qin Yingying , Chen Zi-Jiang , Zhao Shidou
Published: January 2022

Primordial follicle activation is fundamental for folliculogenesis and for the maintenance of fertility. An effective therapeutic strategy for patients with premature ovarian insufficiency (POI) is to promote the activation of residual primordial follicles. The secretome of human umbilical cord mesenchymal stromal cells (hUC-MSC-sec) contains several components that might promote the activation of primordial follicles. In the present study, we revealed that treatment with the hUC-MSC-sec significantly increased the proportion of activated primordial follicles in mouse ovaries both in vitro and in vivo. The activating effects of hUC-MSC-sec on primordial follicles were attributed to the activation of the PI3K-AKT signaling pathway by hepatocyte growth factor (HGF). While the effect of the hUC-MSC-sec was attenuated by the neutralizing antibodies against HGF, application of exogenous HGF alone also promoted the activation of primordial follicles. Furthermore, we demonstrated that HGF promoted the expression of KITL in granulosa cells by binding with the HGF receptor c-Met, thereby increasing the activity of the PI3K-AKT signaling pathway to activate primordial follicles. Taken together, our findings demonstrate that hUC-MSC-sec promotes primordial follicle activation through the functional component HGF to increase the PI3K-AKT signaling activity, highlighting the application of the hUC-MSC-sec or HGF for the treatment of POI patients.

Graphical abstract
On the Robosphere: A Philosophical Explication of the Socio-technical Status of Social Robots
Authors: Lamola Malesela John
Published: January 2022

As the Fourth Industrial Revolution advances, socially-situated robots are increasingly not exclusively human-like (i.e. humanoids). They also include socially interactive animaloids. How does this myriad of socially intelligent artefacts emerge as members of a cyber-physical social system in which they are accorded the standing of social robots? And how are we to account for the nature of the universe-of-meaning that emerges from this human-artificial social reality? Utilizing conceptual tools derived from the philosophical fields of phenomenology and “new materialism”, I proffer a theoretic account of robotic sociality. I postulate how robots become members of a cyber-physical social network that is cohabited with sapient humans. Two novel functional constructs are introduced in the process: “the humanoidic” and “the robosphere”. The former illuminates that spontaneous bestowal of sociality on robots is tantamount to a recognition of their social agency. I then demonstrate how this psychical process of the recognition of these humanoidic artefacts instantiates an emergence of a shared human–robot cyber-physical world of relational meaning-making, a robosphere. As a corroboration of the self-manifestation of the robosphere as a concrete social system, it is shown that Industry 4.0 adumbrates Society 4.0, a cybernetic social formation, and the envisioned advance of this into the more technocratic super-smart Society 5.0.
Characterization of groundwater in the 'Tamnean' Plutonic Suite aquifers using hydrogeochemical and multivariate statistical evidence: a study in the Garu-Tempane District, Upper East Region of Ghana
Authors: Okofo Louis Boansi , Bedu-Addo Kenneth , Martienssen Marion
Published: January 2022

The 'Tamnean' Plutonic Suite aquifer is the main public water supply for the Garu-Tempane District. Thus, hydrogeochemical characterization is essential to provide valuable insights into pollution sources and the main controls on groundwater chemistry. In this regard, multivariate statistical methods, conventional hydrochemical graphical methods, and various ionic ratios complemented with PHREEQC geochemical modelling were carried out using 38 groundwater samples collected from the Tamnean Plutonic Suite aquifers, Ghana. The ionic ratio plots, the chloro-alkaline indices, and the graphical diagrams indicate that the major sources of groundwater chemistry are silicate mineral dissolution and cation exchange coupled with the leaching of domestic solid waste and nitrogen-based fertilizers. The Q-mode hierarchical cluster analysis reveals three spatial groundwater zones. Groundwater from recharge areas consists of Ca–Na–HCO3 water types in cluster 1. The intermediate zone is characterized by Ca–Mg–Na–HCO3 water types of moderate ionic compositions in cluster 2, and this evolves into a discharge zone in cluster 3 mainly of Ca–Mg–Na–HCO3–NO3 water types. The principal component analysis (PCA) reveals three factors, which account for 81% of the total variance, and this suggests most of the groundwater chemistry had longer interaction with the lithological materials. The PHREEQC geochemical modelling consisting of mineral saturation index indicates that groundwater is mostly supersaturated with respect to dolomite and undersaturated with respect to calcite, anhydrite, fluorite, gypsum, and halite. Based on the water quality index, the groundwater in the district is generally suitable for drinking water purposes. All the samples are within the World Health Organization acceptable limits for drinking water except for lower pH, elevated nitrate and bromide concentrations in some of the wells. About 10.5% of the groundwater samples are contaminated with nitrate, which may pose a health danger to the inhabitants in the communities. The finding of this study will not only contribute to solving the research paucity regarding the Tamnean Plutonic Suite aquifers in the Garu-Tempane District but will serve as a valuable document for water managers and decision-makers in Ghana.
Theoretical analysis and parametric investigation of an innovative helical air gap membrane desalination system
Authors: Shahu Vandita T. , Thombre Shashikant B.
Published: January 2022

A helical air gap membrane desalination (HAGMD) system is designed in the present study. The condenser is designed as a cylindrical shape with helical fins machined on the outer surface of a hollow copper condenser. A detailed theoretical model, studying heat and mass transfer in the HAGMD module, was developed. The theoretical model for a cylindrical system with fins is developed for the first time and is unique in the MD literature. Experimentation was carried out to examine the behavior of the HAGMD module under diverse design and operating conditions. The effect of cold flow rate, feed flow rate, feed temperature, the height of fins, the number of fins, and the length of the module is determined on the performance of the HAGMD system. Permeate flux and gained output ratio (GOR) were considered as the performance indicators of the system. Results showed that permeate flux increases with cold flow rate, feed temperature, feed flow rate, as well as number of fins, while the increase in height of fins negatively affects the flux. Theoretical model and experimental results are found to be in excellent agreement with only 6.7% of error which shows that the present theoretical model is excellent to predict the performance of any HAGMD system. For similar design parameters, the average flux increased by 135% for the finned HAGMD module, with 35 fins over the one with that only for 1 fin. Maximum experimental distillate flux is found to be 20 kg/m2 hr, and GOR is found to be 0.75.