75 research outputs found
Asymptotic Conformal Invariance of SU(2) and Standard Models in Curved Space-time
The asymptotic conformal invariance of some SU(2) model and Standard Model in
curved space-time are investigated. We have examined the conditions for
asymptotic conformal invariance for these models numerically.Comment: 13 pages, Revtex3.
Progressive reduced order modeling: empowering data-driven modeling with selective knowledge transfer
Data-driven modeling can suffer from a constant demand for data, leading to
reduced accuracy and impractical for engineering applications due to the high
cost and scarcity of information. To address this challenge, we propose a
progressive reduced order modeling framework that minimizes data cravings and
enhances data-driven modeling's practicality. Our approach selectively
transfers knowledge from previously trained models through gates, similar to
how humans selectively use valuable knowledge while ignoring unuseful
information. By filtering relevant information from previous models, we can
create a surrogate model with minimal turnaround time and a smaller training
set that can still achieve high accuracy. We have tested our framework in
several cases, including transport in porous media, gravity-driven flow, and
finite deformation in hyperelastic materials. Our results illustrate that
retaining information from previous models and utilizing a valuable portion of
that knowledge can significantly improve the accuracy of the current model. We
have demonstrated the importance of progressive knowledge transfer and its
impact on model accuracy with reduced training samples. For instance, our
framework with four parent models outperforms the no-parent counterpart trained
on data nine times larger. Our research unlocks data-driven modeling's
potential for practical engineering applications by mitigating the data
scarcity issue. Our proposed framework is a significant step toward more
efficient and cost-effective data-driven modeling, fostering advancements
across various fields
Computational Synthesis of Wearable Robot Mechanisms: Application to Hip-Joint Mechanisms
Since wearable linkage mechanisms could control the moment transmission from
actuator(s) to wearers, they can help ensure that even low-cost wearable
systems provide advanced functionality tailored to users' needs. For example,
if a hip mechanism transforms an input torque into a spatially-varying moment,
a wearer can get effective assistance both in the sagittal and frontal planes
during walking, even with an affordable single-actuator system. However, due to
the combinatorial nature of the linkage mechanism design space, the topologies
of such nonlinear-moment-generating mechanisms are challenging to determine,
even with significant computational resources and numerical data. Furthermore,
on-premise production development and interactive design are nearly impossible
in conventional synthesis approaches. Here, we propose an innovative autonomous
computational approach for synthesizing such wearable robot mechanisms,
eliminating the need for exhaustive searches or numerous data sets. Our method
transforms the synthesis problem into a gradient-based optimization problem
with sophisticated objective and constraint functions while ensuring the
desired degree of freedom, range of motion, and force transmission
characteristics. To generate arbitrary mechanism topologies and dimensions, we
employed a unified ground model. By applying the proposed method for the design
of hip joint mechanisms, the topologies and dimensions of non-series-type hip
joint mechanisms were obtained. Biomechanical simulations validated its
multi-moment assistance capability, and its wearability was verified via
prototype fabrication. The proposed design strategy can open a new way to
design various wearable robot mechanisms, such as shoulders, knees, and ankles.Comment: 28 pages, 7 figures, Supplementary Material
Identification and purification of a soluble region of BubR1: a critical component of the mitotic checkpoint complex
The mitotic checkpoint complex (MCC) ensures the fidelity of chromosomal segregation, by delaying the onset of anaphase until all sister chromatids have been properly attached to the mitotic spindle. In essence, this MCC-induced delay is achieved via the inhibition of the anaphase-promoting complex (APC). Among the components of the MCC, BubR1 plays two major roles in the functions of the mitotic checkpoint. First, BubR1 is able to inhibit APC activity, either by itself or as a component of the MCC, by sequestering a APC coactivator, known as Cdc20. Second, BubR1 activates mitotic checkpoint signaling cascades by binding to the centromere-associated protein E, a microtubule motor protein. Obtaining highly soluble BubR1 is a prerequisite for the study of its structure. BubR1 is a multi-domain protein, which includes a KEN box motif, a mad3-like region, a Bub3 binding domain, and a kinase domain. We obtained a soluble BubR1 construct using a three-step expression strategy. First, we obtained two constructs from BLAST sequence homology searches, both of which were expressed abundantly in the inclusion bodies. We then adjusted the lengths of the two constructs by secondary structure prediction, thereby generating partially soluble constructs. Third, we optimized the solubility of the two constructs by either chopping or adding a few residues at the C-terminus. Finally, we obtained a highly soluble BubR1 construct via the Escherichia coli expression system, which allowed for a yield of 10.8 mg/L culture. This report may provide insight into the design of highly soluble constructs of insoluble multi-domain proteins
Taurine in drinking water recovers learning and memory in the adult APP/PS1 mouse model of Alzheimer's disease
Alzheimer's disease (AD) is a lethal progressive neurological disorder affecting the memory. Recently, US Food and Drug Administration mitigated the standard for drug approval, allowing symptomatic drugs that only improve cognitive deficits to be allowed to accelerate on to clinical trials. Our study focuses on taurine, an endogenous amino acid found in high concentrations in humans. It has demonstrated neuroprotective properties against many forms of dementia. In this study, we assessed cognitively enhancing property of taurine in transgenic mouse model of AD. We orally administered taurine via drinking water to adult APP/PS1 transgenic mouse model for 6 weeks. Taurine treatment rescued cognitive deficits in APP/PS1 mice up to the age-matching wild-type mice in Y-maze and passive avoidance tests without modifying the behaviours of cognitively normal mice. In the cortex of APP/PS1 mice, taurine slightly decreased insoluble fraction of Aβ. While the exact mechanism of taurine in AD has not yet been ascertained, our results suggest that taurine can aid cognitive impairment and may inhibit Aβ-related damages.MIT International Science and Technology InitiativesKorea Health Industry Development Institute (H14C04660000)Korea Institute of Science and Technology (Open Research 2E24582)Korea Institute of Science and Technology (Flagship 2E25023
Quaternary structures of Vac8 differentially regulate the Cvt and PMN pathways.
Armadillo (ARM) repeat proteins constitute a large protein family with diverse and fundamental functions in all organisms, and armadillo repeat domains share high structural similarity. However, exactly how these structurally similar proteins can mediate diverse functions remains a long-standing question. Vac8 (vacuole related 8) is a multifunctional protein that plays pivotal roles in various autophagic pathways, including piecemeal microautophagy of the nucleus (PMN) and cytoplasm-to-vacuole targeting (Cvt) pathways in the budding yeast Saccharomyces cerevisiae. Vac8 comprises an H1 helix at the N terminus, followed by 12 armadillo repeats. Herein, we report the crystal structure of Vac8 bound to Atg13, a key component of autophagic machinery. The 70-angstrom extended loop of Atg13 binds to the ARM domain of Vac8 in an antiparallel manner. Structural, biochemical, and in vivo experiments demonstrated that the H1 helix of Vac8 intramolecularly associates with the first ARM and regulates its self-association, which is crucial for Cvt and PMN pathways. The structure of H1 helix-deleted Vac8 complexed with Atg13 reveals that Vac8[Delta 19-33]-Atg13 forms a heterotetramer and adopts an extended superhelical structure exclusively employed in the Cvt pathway. Most importantly, comparison of Vac8-Nvj1 and Vac8-Atg13 provides a molecular understanding of how a single ARM domain protein adopts different quaternary structures depending on its associated proteins to differentially regulate 2 closely related but distinct cellular pathways
Differential Proteome Profiling Using iTRAQ in Microalbuminuric and Normoalbuminuric Type 2 Diabetic Patients
Diabetic nephropathy (DN) is a long-term complication of diabetes mellitus that leads to end-stage renal disease. Microalbuminuria is used for the early detection of diabetic renal damage, but such levels do not reflect the state of incipient DN precisely in type 2 diabetic patients because microalbuminuria develops in other diseases, necessitating more accurate biomarkers that detect incipient DN. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify urinary proteins that were differentially excreted in normoalbuminuric and microalbuminuric patients with type 2 diabetes where 710 and 196 proteins were identified and quantified, respectively. Some candidates were confirmed by 2-DE analysis, or validated by Western blot and multiple reaction monitoring (MRM). Specifically, some differentially expressed proteins were verified by MRM in urine from normoalbuminuric and microalbuminuric patients with type 2 diabetes, wherein alpha-1-antitrypsin, alpha-1-acid glycoprotein 1, and prostate stem cell antigen had excellent AUC values (0.849, 0.873, and 0.825, resp.). Moreover, we performed a multiplex assay using these biomarker candidates, resulting in a merged AUC value of 0.921. Although the differentially expressed proteins in this iTRAQ study require further validation in larger and categorized sample groups, they constitute baseline data on preliminary biomarker candidates that can be used to discover novel biomarkers for incipient DN
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