bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Control Formulation for Manual Wheelchair Locomotion Simulations: Influence of Anteroposterior Stability
Authors: Loisel Jade , Rouvier Théo , Hybois Samuel , Bascou Joseph , Sauret Christophe 
Published: August 2023

Abstract
Manual wheelchair (MWC) locomotion exposes the user's upper-body to large and repetitive loads, which can lead to upper limbs pain and injuries. A thinner understanding of the influence of MWC settings on propulsion biomechanics could allow for a better adaptation of MWC configuration to the user, thus limiting the risk of developing such injuries. Advantageously compared to experimental studies, simulation methods allow numerous configurations to be tested. Recent studies have developed predictive locomotion simulation using optimal control methods. However, those models do not consider MWC anteroposterior stability, potentially resulting in unreasonable propulsion strategies. To this extent, this study aimed at confirming if constraining MWC anteroposterior stability in the optimal control formulation could lead to a different simulated movement. For this purpose, a four-link rigid-body system was used in a forward dynamics optimization paired with an anteroposterior stability constraint to predict MWC locomotion dynamics of the upper limbs during both startup and steady-state propulsion. Simulation results indicated the occurrence of MWC tipping when stability was not constrained, and that the constrained optimal control algorithm predicted different propulsion strategies. Hence, further proceedings of MWC locomotion simulation and optimal control investigations should take the anteroposterior stability into account to achieve more realistic simulations. Additionally, the implementation of the anteroposterior stability constrains unexpectedly resulted in a reduction of the computational time.
Physical Insight Into Whoosh Noise in Turbocharger Compressors Using Computational Fluid Dynamics
Authors: Dehner Rick , Selamet Ahmet , Sriganesh Pranav , Banerjee Deb , Selamet Emel , Karim Ahsanul , Brewer Todd , Morelli Anthony 
Published: August 2023

Abstract
Whoosh is typically the primary noise concern for turbocharger centrifugal compressors without ported shroud recirculating casing treatments, utilized for spark-ignition automotive applications. Whoosh is characterized by broadband elevation of noise in approximately the 4–13 kHz range, where the lower frequency boundary is dictated by the cut-on frequency of the first multidimensional acoustic mode. At mid-to-low compressor flow rates, swirling, reversed flow emanates from the leading-edge tip region of the main impeller blades, comprising an annular zone at the inducer plane. High velocity gradients are observed near the shear layer between the bidirectional forward and reverse flow which results in the formation of rotating instability cells. Whoosh noise is generated due to the interaction of these rotating instabilities with the leading edge of main impeller blades. Along a line of constant rotational speed, whoosh noise exhibits a dome-like character, where its maximum value occurs in the mid-to-low flow region and the levels decrease at elevated and reduced mass flow rates. To provide insight into the variation of broadband whoosh noise with flowrate, this work includes experimentally validated computational fluid dynamics predictions for five mass flow rates at a fixed rotational speed. These predictions span the constant speed flow range from just below the peak efficiency to near the surge boundary. Computational predictions capture the physical mechanism responsible for the dome-like character of whoosh noise as a function of flowrate at a given rotational speed.
Virtual Dynamics Model for Five-Axis Machining of Thin-Walled Blades
Authors: Karimi Behnam , Altintas Yusuf 
Published: August 2023

Abstract
The five-axis ball-end milling dynamics of thin-walled blades is presented. The cutting forces are predicted from the ball-end mill–blade geometry engagement maps along the toolpath. The Frequency Response Function (FRF) of the thin-walled blade is predicted using Finite Element shell elements, and it is updated along the toolpath as the metal is removed. The predicted cutting forces are applied on both the workpiece and tool FRFs to predict the forced vibrations and chatter stability at each tool location. A simplified method to update the cutter-workpiece engagement (CWE) is used to obtain the three-dimensional stability lobe diagram at each desired point on the blade. The integrated model is used to simulate the five-axis machining of thin-walled blades in the digital environment. The proposed digital model is experimentally validated by machining a series of thin-walled rectangular plates and a twisted fan blade.
A Dynamic Reliability Prognosis Method for Reusable Spacecraft Mission Planning Based on Digital Twin Framework
Authors: Gao Bo , Ye Yumei , Pan Xin , Yang Qiang , Xie Weihua , Meng Songhe , Huo Yanyan 
Published: August 2023

Abstract
Reusable spacecraft has great potential in reducing space launch cost. Structural reliability evaluation is critical for mission planning of reusable spacecraft. A dynamic reliability prognosis method based on digital twin framework is proposed for mission planning in the paper. In this method, Uncertainties integration and dynamic model updating are implemented through a dynamic Bayesian network. A maintenance point is set when the predicted structural reliability level is lower than a threshold or unexpected conditions such as landing impact occur. Then, inspected data can be assimilated by the framework to dynamically update the structural reliability. Thus, it supports dynamic adjustment of maintenance interval, early warning of structure failure, and mission planning with quantified risk. A numerical example considering single point crack growth under fatigue load and landing impact of a simplified spacecraft structure is used for demonstration. Results show that the crack size predictions can be calibrated by inspected data and its uncertainties can be reduced. The proper selection of landing impact probability in reliability prediction is helpful to control the maintenance interval. The reliability of the spacecraft can be increased through model updating with new inspected data, representing a potential lifetime extension can be realized by the proposed method.
The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates
Authors: Anwar Imran J. , Berman Dora M. , DeLaura Isabel , Gao Qimeng , Willman Melissa A. , Miller Allison , Gill Alan , Gill Cindy , Perrin Steve , Ricordi Camillo , Ruiz Philip , Song Mingqing , Ladowski Joseph M. , Kirk Allan D. , Kenyon Norma S. 
Published: August 2023

Prior studies of anti-CD40 ligand (CD40L)–based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An anti-CD40L-specific monoclonal antibody, AT-1501 (Tegoprubart), was engineered to minimize risk of thromboembolic complications by reducing binding to Fcγ receptors expressed on platelets while preserving binding to CD40L. AT-1501 was tested in both a cynomolgus macaque model of intrahepatic islet allotransplantation and a rhesus macaque model of kidney allotransplantation. AT-1501 monotherapy led to long-term graft survival in both islet and kidney transplant models, confirming its immunosuppressive potential. Furthermore, AT-1501–based regimens after islet transplant resulted in higher C-peptide, greater appetite leading to weight gain, and reduced occurrence of cytomegalovirus reactivation compared with conventional immunosuppression. These data support AT-1501 as a safe and effective agent to promote both islet and kidney allograft survival and function in nonhuman primate models, warranting further testing in clinical trials.
The mature N-termini of
Plasmodium
effector proteins confer specificity of export
Authors: Hasan Muhammad M. , Polino Alexander J. , Mukherjee Sumit , Vaupel Barbara , Goldberg Daniel E. 
Published: August 2023

ABSTRACT

The intraerythrocytic malaria parasite
Plasmodium falciparum
exports hundreds of proteins into the host red blood cell (RBC). Most are targeted to the endoplasmic reticulum (ER) by a stretch of hydrophobic amino acids and cleaved further downstream at a conserved motif called the
Plasmodium
Export Element (PEXEL) by the ER protease plasmepsin V (PM V). The mature effectors then travel through the secretory pathway to the parasitophorous vacuole (PV) that surrounds the parasite. There, PEXEL proteins are somehow recognized as export-destined proteins, as opposed to PV-resident proteins, and are selectively translocated out into the RBC. The mature N-terminus appears to be important for export. There is conflicting data on whether PM V cleavage is needed for proper export or whether any means of generating the mature N-terminus would suffice. We replaced the PEXEL-containing N-terminal sequence of an exported GFP reporter with a signal peptide sequence and showed that precise cleavage by signal peptidase, generating the proper mature N-terminus, yields export competence. Expressing a construct with only the native ER targeting signal without the PM V cleavage site dramatically decreased the amount of a mature PEXEL reporter, indicating that the hydrophobic stretch lacks an efficient cleavage signal. Therefore, the PEXEL motif functions as a specialized signal cleavage site when appropriately located after an ER targeting sequence. Our data suggest that PM V cleavage and RBC export are two independent events for PEXEL proteins. We also tested and rejected the hypothesis that an alpha-helical mature N-terminus is necessary for export.

IMPORTANCE
Malaria parasites export hundreds of proteins to the cytoplasm of the host red blood cells for their survival. A five amino acid sequence, called the PEXEL motif, is conserved among many exported proteins and is thought to be a signal for export. However, the motif is cleaved inside the endoplasmic reticulum of the parasite, and mature proteins starting from the fourth PEXEL residue travel to the parasite periphery for export. We showed that the PEXEL motif is dispensable for export as long as identical mature proteins can be efficiently produced via alternative means in the ER. We also showed that the exported and non-exported proteins are differentiated at the parasite periphery based on their mature N-termini; however, any discernible export signal within that region remained cryptic. Our study resolves a longstanding paradox in PEXEL protein trafficking.
A
Toxoplasma gondii
lipoxygenase-like enzyme is necessary for virulence and changes localization associated with the host immune response
Authors: Ramírez-Flores Carlos J. , Erazo Flores Billy Joel , Tibabuzo Perdomo Andrés M. , Barnes Katie L. , Wilson Sarah K. , Mendoza Cavazos Carolina , Knoll Laura J. 
Published: August 2023

ABSTRACT

While the asexual cycle of
Toxoplasma gondii
can occur in any warm-blooded animal, the sexual cycle is restricted to the feline intestine. We previously determined that because cats lack delta-6-desaturase activity in their intestines, they build up excess linoleic acid, which signals
T. gondii
to undergo sexual development. We hypothesized that
T. gondii
oxygenates linoleic acid to signal sexual development, so we examined the
T. gondii
genome for lipoxygenases-like enzymes (TgLOXL) enzymes. We identified seven TgLOXLs that were at least 100-fold more abundant in the cat intestinal versus the tissue culture tachyzoite stage. Parasites deleted in TgLOXL1 (TgΔLOXL1) had no significant growth differences in tissue culture fibroblast cells. Because the sexual development assay begins with brain cysts, we infected mice with TgΔLOXL1 and were surprised to find that TgΔLOXL1 had reduced virulence. The TgΔLOXL1 parasitemia was reduced by 3 d post-infection and largely cleared by 7 d post-infection. At 3 d post-infection, the cytokines interferon gamma (IFN-γ), IL-6, MCP-1, and TNF-α were significantly reduced in TgΔLOXL1-infected mice, which prompted us to examine TgΔLOXL1 in IFN-γ KO mice. We found that IFN-γ KO mice infected with TgΔLOXL1 succumbed to acute infection with the same kinetics as the parental and complemented strains, suggesting that TgLOXL1 plays a role in the IFN-γ signaling cascade. In tissue culture fibroblasts, TgLOXL1 was localized within the parasite, but in leukocytes from infected mice and activated macrophages, TgLOXL1 was localized within the host cytoplasm. These results suggest that TgLOXL1 changes localization in response to host immune activation.

IMPORTANCE

Lipoxygenases (LOXs) are enzymes that catalyze the deoxygenation of polyunsaturated fatty acids such as linoleic and arachidonic acid. These modifications create signaling molecules that are best characterized for modulating the immune response. Deletion of the first lipoxygenase-like enzyme characterized for
Toxoplasma gondii
(TgLOXL1) generated a less virulent strain, and infected mice showed a decreased immune response. This virulence defect was dependent on the mouse cytokine interferon gamma IFNγ. TgLOXL1 changes location from inside the parasite in tissue culture conditions to vesicular structures within the host immune cells during mouse infection. These results suggest that TgLOXL1 plays a role in the modification of the host immune response in mice.
A new hypothesis on BV etiology: dichotomous and crisscrossing categorization of complex versus simple on healthy versus BV vaginal microbiomes
Authors: Ma Zhanshan (Sam) 
Published: August 2023

ABSTRACT

It has been estimated that bacterial vaginosis (BV) influences as many as one-third of women, but its etiology remains unclear. A traditionally held view is that dominance by
Lactobacillus
is the hallmark of a healthy vaginal microbiome (VM) and lack of dominance may make women BV-prone. A more recent characterization is that the human VMs can be classified into five major types, four of which possess type-specific dominant species of
Lactobacillus
. The remaining one (type IV) is not dominated by
Lactobacillus
and contains a handful of strictly anaerobic bacteria. Nevertheless, exceptions to the first hypothesis have been noticed from the very beginning, and there is not a definite relationship, suggested yet, between the five VM types and BV status. Here, we propose a novel hypothesis that assumes the existence of four VM types from dichotomous crisscrossing of “complex versus simple (high-diversity or low-dominance versus low-diversity or high-dominance)” on “healthy versus BV” (the four essential dimensions of VMs). We comprehensively test the hypothesis with 7,958 VM samples by demonstrating the statistically significant differences between the four VM types in community diversity, composition, dominance, heterogeneity, and stochasticity, and by identifying unique/enriched species in each VM type. We further verified the categorization (hypothesis) by using six machine learning (ML) algorithms, including deep learning artificial intelligence (AI) technology, to reclassify the randomly mixed VM samples into four respective types and achieved 85%–100% classification precisions. Our hypothesis provides a foundation for further investigating the etiology and automatic diagnosis of BV based on inexpensive amplicon sequencing and AI technology.

IMPORTANCE

BV may influence as many as one-third of women, but its etiology remains unclear. A traditional view is that dominance by
Lactobacillus
is the hallmark of a healthy vaginal microbiome and lack of dominance may make women BV-prone. Recent studies show that the human VMs can be classified into five major types, four of which possess type-specific dominant species of
Lactobacillus
. The remaining one (type IV) is not dominated by
Lactobacillus
and contains a handful of strictly anaerobic bacteria. Nevertheless, exceptions to the first hypothesis have been noticed from the very beginning, and there is not a definite relationship, suggested yet, between the five VM types and BV status. Here, we propose and test a novel hypothesis that assumes the existence of four VM types from dichotomous crisscrossing of “complex versus simple (high diversity or low dominance versus low diversity or high dominance)” on “healthy versus BV.” Consequently, there are simple BV versus complex BV.
Development of the early-life gut microbiome and associations with eczema in a prospective Chinese cohort
Authors: Cheung Man Kit , Leung Ting Fan , Tam Wing Hung , Leung Agnes S. Y. , Chan Oi Man , Ng Rita W. Y. , Yau Jennifer W. K. , Yuen Lai-yuk , Tong Sylvia L. Y. , Ho Wendy C. S. , Yeung Apple C. M. , Chen Zigui , Chan Paul K. S. 
Published: August 2023

ABSTRACT

The first few years of life is a key period for the development of the gut microbiome. However, our current understanding of this topic is largely biased toward Western populations. In this study, we characterized the development and determinants of the gut microbiome in a prospective cohort of 112 term Chinese children by sequencing 713 stool samples collected at nine time points from birth to 3 years of age using 16S rRNA gene sequencing. We revealed alterations in the composition and alpha and beta diversities of the gut microbiota across the first 3 years of life. We identified mode of delivery, feeding mode, and intrapartum antibiotics as the major determinants of the early-life gut microbiome, the effects of all of which persisted up to 12 months. Importantly, by conducting a nested case–control study, we showed that alterations in the infant gut microbiota precede the development of eczema. Interestingly, we identified a depletion of
Bacteroides
and an enrichment of
Clostridium sensu stricto 1
in the gut microbiome of infants with eczema at 1 year old. The same patterns were also observed in C-section-born infants within the same time frames, suggesting a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema. Our study has revealed important associations between the gut microbiome and eczema in infancy and has established the basis for potential prevention/treatment of eczema via modulation of the gut microbiota.

IMPORTANCE

Eczema is a major allergic disease in children, which is particularly prevalent in Chinese children during their first year of life. In this study, we showed that alterations in the infant gut microbiota precede the development of eczema in a prospective Chinese cohort. In particular, we discovered enrichments of the genera
Clostridium sensu stricto 1
and
Finegoldia
in the cases at 3 and 1 month of age, respectively, which may represent potential targets for intervention to prevent eczema. Besides, we identified a depletion of
Bacteroides
from 1 to 6 months of age and an enrichment of
Clostridium sensu stricto 1
at 3 months in the eczema cases, patterns also observed in C-section-born infants within the same time frames, providing first evidence to support a role of the gut microbiota in previously reported associations between C-section and increased risk of eczema in infancy.
Validation of a comorbidity questionnaire in patients with neurological disorders
Authors: Vijiaratnam Nirosen , Vadera Shree , Lefringhausen Katharina , Girges Christine , Schrag Anette 
Published: August 2023

RationalSeveral tools exist to assess comorbidities in neurological disorders, the most widely used being the Charlson Comorbidity Index (CCI), but it has several limitations. The Comorbidity and General Health Questionnaire (CGHQ) is a newly designed tool, which includes additional comorbidities associated with health-related quality of life (HR-QOL) and outcomes in neurological disorders.Aims and objectivesTo assess the feasibility and validity of the CGHQ in patients with neurological disease.MethodTwo hundred patients attending a general neurological clinic were invited to complete the CGHQ along with the EQ-5D-5L questionnaire. The CCI was simultaneously completed by the assessor. CGHQ comorbidity scores were compared with CCI, symptom burden and EQ-5D-5L scores.ResultsThe CGHQ captured 22 additional comorbidities not included on the CCI and more comorbidities were endorsed on the CGHQ. The CGHQ correlated weakly to moderately with CCI comorbidity scores. While both the CGHQ and CCI correlated negatively with the EQ-5D-5L Visual Analogue Scale, only the CGHQ correlated negatively with the EQ-5D-5L summary index. The CGHQ but not the CCI correlated strongly and positively with symptom burden scores.ConclusionThe CGHQ allows a more comprehensive assessment of comorbidities than the CCI and better correlates with patients’ overall symptom burden and HR-QOL in neurological patients.
Do markers of adiposity and glycaemia mediate the association between low carbohydrate diet and cardiovascular risk factors: findings from the UK National Diet and Nutrition Survey (NDNS) 2008–2016
Authors: Tramontt Cláudia Raulino , Mouti Saad , Lima Do Vale Marjorie , Li Xunhan , Golubic Rajna , Ray Sumantra 
Published: August 2023

ObjectivesTo examine the associations between low carbohydrate diet (LCD) and conventional cardiovascular risk factors and investigate whether these associations are mediated by body mass index (BMI), waist circumference (WC) and haemoglobin A1c (HbA1c) applying causal mediation analyses.MethodsWe included 3640 adults aged 45–80 years from the UK National Diet and Nutrition Survey programme (2008–2016) with data on dietary intake, anthropometric and biochemical parameters. Four hypothetical interventions were examined: (1) LCD, (2) Low carbohydrate (LC) and high fibre diet (LCHF), (3) LC and high saturated fat diet (LCHS) and (4) LC and high unsaturated fat diet (LCHU). BMI and WC were used as markers of obesity. Biochemical markers included HbA1c, total cholesterol, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, triglycerides, systolic and diastolic blood pressure and C reactive protein (CRP). BMI, WC and HbA1c were used as a mediator of the effects. The analysis was adjusted for sociodemographic characteristic, smoking, estimated total energy intake, alcohol consumption and antihypertensive medication. To identify a potential causal effect of LCD on cardiovascular disease (CVD) risk, we estimated the average treatment effect, and corresponding p values and CI for the total, indirect and direct effect of the treatment on the outcome.ResultsBMI, WC and HbA1c fully mediated the association between LCD and triglycerides and fully mediated the effects of LCHF on LDL, although BMI and WC were not sufficient to fully mediate the effects of LCHF on triglycerides and CRP. BMI alone fully mediated the effects of LCHS on HbA1c, triglycerides, LDL and CRP. None of these mediators explained the effect of LCHU on CVD risk markers.ConclusionThe causal hypotheses tested in this study demonstrate that individuals on LCD with high fibre intakes improved their CVD markers as expected, but those on LCD who increase fat intake had no effects on CVD markers mediated by obesity and diabetes.