bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redundant Non-Serial Implicit Manipulator Kinematics and Dynamics
Authors: Haug Edward J. 
Published: April 2024

Abstract
Redundant non-serial manipulators that include a spectrum of parallel and non-parallel heavy load bearing construction and material handling equipment are treated, using foundations of differential geometry. Kinematics of this category of manipulator are defined in manipulator configuration space by algebraic equations in input and output coordinates that cannot be explicitly solved for either as a function of the other. New sets called assembly components of manipulator configuration space are defined that partition the space into maximal, path-connected, disjoint, topological components. All configurations within an assembly component can be connected by one or more continuous paths within that component, but configurations in different assembly components cannot be connected by continuous paths. Forward and inverse kinematically singular configurations are characterized by criteria that partition each assembly component into path-connected, singularity-free assembly components in which equations of kinematics and dynamics are well behaved. It is shown that a generalized inverse velocity-based kinematic formulation that is problematic for serial manipulators is likewise plagued with problems for non-serial implicit manipulators that can be avoided using the methods presented. Singularity-free differentiable manipulator configuration space components are defined and parameterized by both input and operational coordinates, leading to well-posed ordinary differential equations of manipulator dynamics in both input and operational coordinates. Three typical applications and associated model problems are studied throughout the paper to illustrate the methods and results presented.
Online Self-Calibration of Cable-Driven Parallel Robots Using Covariance-Based Data Quality Assessment Metrics
Authors: Caverly Ryan J. , Cheah Sze Kwan , Bunker Keegan R. , Patel Samir , Sexton Niko , Nguyen Vinh L. 
Published: April 2024

Abstract
This article presents an algorithm to perform self-calibration of cable-driven parallel robots (CDPRs), where the CDPR’s end-effector pose is estimated in conjunction with the calibration of biases in CDPR’s measurements. Two new metrics, known as the position dilution of precision (PDOP) and orientation dilution of precision (ODOP), are introduced as a means to quantify the quality of data collected with regards to self-calibration. These metrics are based on a covariance matrix that is computed online as part of the proposed self-calibration algorithm, which results in the PDOP and ODOP directly corresponding to the standard deviation of the position and orientation errors, respectively. These metrics are used to intuitively select which data points contribute to improved calibration, resulting in a computationally efficient algorithm requiring few data points to maintain accurate calibration. In addition, the PDOP and ODOP provide a means to assess when sufficient calibration data have been collected. Numerical results involving an inverse kinematic simulation with rigid cables and a dynamic simulation with flexible cables indicate that the proposed algorithm is capable of performing self-calibration in a computationally efficient manner. Moreover, the simulation results indicate that the proposed PDOP and ODOP metrics result in smaller position and orientation errors when used to prune the dataset compared to the observability indices found in the literature. Accuracy of the proposed algorithm is also confirmed through experiments when compared to ground-truth pose data.
NiCrBSi/WC Composite Claddings Processed on AISI 316L Steel Alloy by the Direct Laser Deposition Process: Studies on Dry Sliding Wear Behavior and Wear Mechanism Maps
Authors: Birada Lakshmi Manasa , Vyshnavi Pullela , Rao Thella Babu 
Published: April 2024

Abstract
This study presented the wear behavior of the NiCrBSi/WC composite claddings processed on an AISI 316L steel alloy substrate by laser cladding approach. The scanning electron microscope (SEM) morphology of the claddings has shown excellent substrate–cladding interface bonding, good WC particulate distribution, and no noticeable cracks and voids. The electron dispersion spectroscope (EDS) spectra have confirmed the presence of respective NiCrBSi alloy matrix and WC elements. The XRD spectra have identified various phases and compounds such as gamma-Ni, FeNi3, Ni3B, Cr23C6, Ni3Si, and W2C commonly in all the processed composite claddings. The microhardness of the claddings was measured between 791 and 1086 HV0.2 for increasing the reinforcement WC particulate percentage from 15 wt% to 60 wt%. It is about 470% surface hardness enhancement with the processed composite claddings compared with the substrate alloy. The reinforcement of WC from 15 wt% to 60 wt% with the composite claddings resulted in wear resistance enhancement from 21.85% to 60.64% and the coefficient of friction from 56.87% to 77.92% against the substrate. The wear-rate maps and their respective cladding's worn surface morphology have described the wear mechanisms typically as adhesive, abrasive, oxidation, and delamination. The wear mechanisms are mainly influenced by the WC particulate percentage. The increased WC particulate content has increased the dominance of the abrasive wear mechanism while reducing the window of the adhesive wear mechanism. The windows of various wear mechanisms and their ranges, such as adhesive 0.0033 to 0.028, abrasion 0.010 to 0.067, oxidation 0.012 to 0.093, and delamination 0.015 to 0.120 mm3/m, for NiCrBSi/WC composite claddings comprehensibly represented the wear behavior for the varied conditions of dry sliding wear parameters.
Analytic Center-Based Tension Distribution for Cable-Driven Platforms
Authors: Di Paola Vincenzo , Goldsztejn Alexandre , Zoppi Matteo , Caro Stéphane 
Published: April 2024

Abstract
A redundant cable-driven platform (CDP) is composed of m cables that exceed the degree-of-freedom (DoF) of the end-effector. The choice of tension along the cables admits infinite solutions. This paper proposes the use of the analytic center to solve the tension distribution problem. Adopting this technique allows finding tensions far from the tension limits, namely, robust as well as tension profiles continuous and differentiable in time. The continuity, differentiability, and uniqueness of the solution are also proven. Moreover, the possibility of including non-linear constraints acting on the tensions (e.g., friction) is a further contribution. The computational time with the proposed approach is compared to the existing techniques to assess its real-time applicability. Finally, several simulations using several cable-driven parallel robots’ (CDPRs) architectures are reported to demonstrate the method’s capabilities.
A randomized assessors-blind clinical trial to evaluate the safety and the efficacy of albendazole alone and in combination with mebendazole or pyrantel for the treatment of
Trichuris trichiura
infection in school-aged children in Lambaréné and surroundings
Authors: Nguema Moure Paul Alvyn , Nzamba Maloum Moustapha , Manouana Gédéon Prince , Laclong Lontchi Roméo-Aimé , Mbong Ngwese Mirabeau , Edoa Jean Ronald , Fréjus Zinsou Jeannot , Meulah Brice , Mahmoudou Saidou , N'noh Dansou Elsy Mirna , Josiane Honkpehedji Yabo , Romeo Adegbite Bayode , Agnandji Selidji Todagbe , Ramharter Michael , Lell Bertrand , Borrmann Steffen , Kremsner Peter G. , Dejon-Agobé Jean Claude , Adegnika Ayôla Akim 
Published: April 2024

ABSTRACT

Helminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three different anthelmintic combinations to treat
Trichuris trichiura
infections. We conducted a randomized assessors-blind clinical trial involving children aged 2–17 years with
T. trichiura
. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and on the second day, albendazole (arm A), mebendazole 500 mg (arm B), or pyrantel 125 mg/kg (arm C). We assessed treatment efficacy using the cure rate (CR) and egg reduction rate (ERR) at 3 and 6 weeks post-treatment. At 3 weeks post-treatment, ERR and CR were highest in study arm A [ERR = 94%, 95% confidence interval (CI): 92–95; CR = 71%; 95% CI: 58–81] compared to the B and C arms. Decrease in ERR was significant only for arm B versus arm A (
P
-value <0.001); decrease in ERR was significant for arms B and C (
P
-value <0.001). No statistical difference was observed in CR when comparing arms A and B (
P
-value =1.00) and C (
P
-value =0.27). At 6 weeks, a decrease in ERR was observed in three arms, significant only for arm C, 81% (95% CI: 78–83). A significant increase in egg counts was observed between 3 and 6 weeks post-treatment. All treatments were safe with mild adverse events. Albendazole 400 mg/day (arm A) showed the highest efficacy against trichuriasis. Nonetheless, this treatment regimen was able to cure half of the treated individuals highlighting concerns about controlling the transmission of
T. trichiura
.

CLINICAL TRIAL

Registered at ClinicalTrials.gov (
NCT04326868
).
Alginate oligosaccharide assimilation by gut microorganisms and the potential role in gut inflammation alleviation
Authors: Ma Xiao-Qing , Wang Bing , Wei Wei , Tan Fang-Cheng , Su Hang , Zhang Jun-Zhe , Zhao Chen-Yang , Zheng Hua-Jun , Feng Yan-Qin , Shen Wei , Yang Jin-Bo , Li Fu-Li 
Published: April 2024

ABSTRACT

Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism
Bacteroides clarus
was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome.

IMPORTANCE
Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.
Promoter regulatory mode evolution enhances the high multidrug resistance of
tmexCD1-toprJ1
Authors: Wang Chengzhen , Yang Jun , Xu Zeling , Lv Luchao , Chen Sheng , Hong Mei , Liu Jian-Hua 
Published: April 2024

ABSTRACT

Antibiotic resistance could rapidly emerge from acquiring the mobile antibiotic resistance genes, which are commonly evolved from an intrinsic gene. The emergence of the plasmid-borne mobilized efflux pump gene cluster
tmexCD1-toprJ1
renders the last-resort antibiotic tigecycline ineffective, although its evolutionary mechanism remains unclear. In this study, we investigate the regulatory mechanisms of the progenitor NfxB-MexCD-OprJ, a chromosomally encoded operon that does not mediate antibiotic resistance in the wild-type version, and its homologs, TNfxB1-TMexCD1-TOprJ1 mediating high-level tigecycline resistance, and TNfxB3-TMexCD3-TOprJ1. Mechanistic studies demonstrated that in
nfxB-mexCD-oprJ
, MexCD expression was under a weaker promoter, P
mexC
and inhibited by a strong repressor NfxB. For
tmexCD1-toprJ1
, TMexCD1 was highly expressed owing to the presence of a strong promoter, P
tmexC1
, and an inactive suppressor, TNfxB1, with a T39R mutation that rendered it unable to bind to promoter DNA. In
tnfxB3-tmexCD3-toprJ1b
, TMexCD3 expression was intermediate because of the local regulator TNfxB3, which binds to two inverted repeat sequences of P
tmexC
. Additionally, TNfxB3 exhibited lower protein expression and weaker DNA binding affinity than its ancestor NfxB, together with their promoter activities difference explaining the different expression levels of
tmexCD-toprJ
homologs. Distinct fitness burdens on these homologs-carrying bacteria were observed due to the corresponding expression level, which might be associated with their global prevalence. In summary, our data depict the mechanisms underlying the evolution and dissemination of an important mobile antibiotic resistance gene from an intrinsic chromosomal gene.

IMPORTANCE

As antibiotic resistance seriously challenges global health, tigecycline is one of the few effective drugs in the pipeline against infections caused by multidrug-resistant pathogens. Our previous work identified a novel tigecycline resistance efflux pump gene cluster
tmexCD1-toprJ1
in animals and humans, together with its various variants, a rising clinical concern. Herein, this study focused on how the local regulation modes of
tmexCD1-toprJ1
evolved to a highly expressed efflux pump. Through comparative analysis between three
tnfxB-tmexCD-toprJ
homologs and their progenitor
nfxB-mexCD-oprJ
, modes, we demonstrated the evolutionary dynamics from a chromosomal silent gene to an active state. We found the de-repression of the local regulator and an increase of the promoter activity work together to promote a high production of drug efflux machines and enhance multidrug resistance. Our findings revealed that TMexCD1-TOprJ1 adopts a distinct evolutionary path to achieve higher multidrug resistance, urgently needing tight surveillance.
Persistence and evolution of
Pseudomonas aeruginosa
following initiation of highly effective modulator therapy in cystic fibrosis
Authors: Armbruster Catherine R. , Hilliam Yasmin K. , Zemke Anna C. , Atteih Samar , Marshall Christopher W. , Moore John , Koirala Junu , Krainz Leah , Gaston Jordan R. , Lee Stella E. , Cooper Vaughn S. , Bomberger Jennifer M. 
Published: April 2024

ABSTRACT

Today, more than 90% of people with cystic fibrosis (pwCF) are eligible for the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy called elexacaftor/tezacaftor/ivacaftor (ETI) and its use is widespread. Given the drastic respiratory symptom improvement experienced by many post-ETI, clinical studies are already underway to reduce the number of respiratory therapies, including antibiotic regimens, that pwCF historically relied on to combat lung disease progression. Early studies suggest that bacterial burden in the lungs is reduced post-ETI, yet it is unknown how chronic
Pseudomonas aeruginosa
populations are impacted by ETI. We found that pwCF remain infected throughout their upper and lower respiratory tract with their same strain of
P. aeruginosa
post-ETI, and these strains continue to evolve in response to the newly CFTR-corrected airway. Our work underscores the continued importance of CF airway microbiology in the new era of highly effective CFTR modulator therapy.

IMPORTANCE

The highly effective cystic fibrosis transmembrane conductance regulator modulator therapy Elexakaftor/Tezacaftor/Ivacaftor (ETI) has changed cystic fibrosis (CF) disease for many people with cystic fibrosis. While respiratory symptoms are improved by ETI, we found that people with CF remain infected with
Pseudomonas aeruginosa
. How these persistent and evolving bacterial populations will impact the clinical manifestations of CF in the coming years remains to be seen, but the role and potentially changing face of infection in CF should not be discounted in the era of highly effective modulator therapy.
Testing multiplexed anti-ASFV CRISPR-Cas9 in reducing African swine fever virus
Authors: Zheng Zezhong , Xu Lei , Gao Yangbin , Dou Hongwei , Zhou Yixuan , Feng Xu , He Xiangjun , Tian Zhen , Song Lingling , Mo Guolong , Hu Jiapan , Zhao Hongye , Wei Hongjiang , Church George M. , Yang Luhan 
Published: April 2024

ABSTRACT

African swine fever (ASF) is a highly fatal viral disease that poses a significant threat to domestic pigs and wild boars globally. In our study, we aimed to explore the potential of a multiplexed CRISPR-Cas system in suppressing ASFV replication and infection. By engineering CRISPR-Cas systems to target nine specific loci within the ASFV genome, we observed a substantial reduction in viral replication
in vitro
. This reduction was achieved through the concerted action of both Type II and Type III RNA polymerase-guided gRNA expression. To further evaluate its anti-viral function
in vivo
, we developed a pig strain expressing the multiplexable CRISPR-Cas-gRNA via germline genome editing. These transgenic pigs exhibited normal health with continuous expression of the CRISPR-Cas-gRNA system, and a subset displayed latent viral replication and delayed infection. However, the CRISPR-Cas9-engineered pigs did not exhibit a survival advantage upon exposure to ASFV. To our knowledge, this study represents the first instance of a living organism engineered via germline editing to assess resistance to ASFV infection using a CRISPR-Cas system. Our findings contribute valuable insights to guide the future design of enhanced viral immunity strategies.

IMPORTANCE

ASFV is currently a devastating disease with no effective vaccine or treatment available. Our study introduces a multiplexed CRISPR-Cas system targeting nine specific loci in the ASFV genome. This innovative approach successfully inhibits ASFV replication
in vitro
, and we have successfully engineered pig strains to express this anti-ASFV CRISPR-Cas system constitutively. Despite not observing survival advantages in these transgenic pigs upon ASFV challenges, we did note a delay in infection in some cases. To the best of our knowledge, this study constitutes the first example of a germline-edited animal with an anti-virus CRISPR-Cas system. These findings contribute to the advancement of future anti-viral strategies and the optimization of viral immunity technologies.
Refining taxonomic identification of microalgae through molecular and genetic evolution: a case study of
Prorocentrum lima
and
Prorocentrum arenarium
Authors: Zheng Danlin , Zou Ligong , Zou Jian , Li Qun , Lu Songhui 
Published: April 2024

ABSTRACT

Species delimitation based on lineage definition has become increasingly popular. However, these methods have been limited, especially for species that lack genomic data and are morphologically similar. The trickiest part for the species identification is that the interspecific and intraspecific boundaries are vague. Taking
Prorocentrum
(Dinophyta) as an example, analysis of cell morphology, growth, and toxin synthesis in both species of
P. lima
and
P. arenarium
does not provide a reliable basis for species delineation. However, through phylogenetic and genetic distance analyses of their ITS and LSU sequences, establishment of evolutionary tree based on orthologous gene sequences, and combining the results of automatic barcode gap discovery and Poisson tree processes models, it was sustained that
P. arenarium
does not belong to the
P. lima
complex and should be considered as an independent species. Interspecies genetic evolution analysis revealed that
P. lima
and
P. arenarium
may contribute to evolutionary direction that favors combating reverse environmental factors. In
P. lima
, viral invasion may be one of the reasons for its large genome size. In the study,
P. lima
complex has been selected as an example to enhance the taxonomic identification of microalgae through molecular and genetic evolution, offering valuable insights into refining taxonomic identification and promoting microbial biodiversity research in other species.

IMPORTANCE

Microalgae, especially the species known as
Prorocentrum
, have received significant attention due to their ability to trigger harmful algal blooms and produce toxins. However, the boundaries between species and within species are ambiguous. Clear and comprehensive species delineation indicates that
Prorocentrum arenarium
should be considered as an independent species, separate from the
Prorocentrum lima
complex. Improving the classification and identification of microalgae through molecular and genetic evolution will provide reference points for other cryptic species.
Prorocentrum
occupy multiple ecological niches in marine environments, and studying their evolutionary direction contributes to understanding their ecological adaptations and community succession.
Unlocking the mechanism of action: a cost-effective flow cytometry approach for accelerating antimicrobial drug development
Authors: Mermans Fabian , De Baets Hanna , García-Timermans Cristina , Teughels Wim , Boon Nico 
Published: April 2024

ABSTRACT

Antimicrobial resistance is one of the greatest challenges to global health. While the development of new antimicrobials can combat resistance, low profitability reduces the number of new compounds brought to market. Elucidating the mechanism of action is crucial for developing new antimicrobials. This can become expensive as there are no universally applicable pipelines. Phenotypic heterogeneity of microbial populations resulting from antimicrobial treatment can be captured through flow cytometric fingerprinting. Since antimicrobials are classified into limited groups, the mechanism of action of known compounds can be used for predictive modeling. We demonstrate a cost-effective flow cytometry approach for determining the mechanism of action of new compounds. Cultures of
Actinomyces viscosus
and
Fusobacterium nucleatum
were treated with different antimicrobials and measured by flow cytometry. A Gaussian mixture mask was applied over the data to construct phenotypic fingerprints. Fingerprints were used to assess statistical differences between mechanism of action groups and to train random forest classifiers. Classifiers were then used to predict the mechanism of action of cephalothin. Statistical differences were found among the different mechanisms of action groups. Pairwise comparison showed statistical differences for 35 out of 45 pairs for
A. viscosus
and for 32 out of 45 pairs for
F. nucleatum
after 3.5 h of treatment. The best-performing random forest classifier yielded a Matthews correlation coefficient of 0.92 and the mechanism of action of cephalothin could be successfully predicted. These findings suggest that flow cytometry can be a cheap and fast alternative for determining the mechanism of action of new antimicrobials.

IMPORTANCE
In the context of the emerging threat of antimicrobial resistance, the development of novel antimicrobials is a commonly employed strategy to combat resistance. Elucidating the mechanism of action of novel compounds is crucial in this development but can become expensive, as no universally applicable pipelines currently exist. We present a novel flow cytometry-based approach capable of determining the mechanism of action swiftly and cost-effectively. The workflow aims to accelerate drug discovery and could help facilitate a more targeted approach for antimicrobial treatment of patients.