bluuebunny/crossref_metadata_2025 huggingface dataset:
Data-Driven Design via Scalable Gaussian Processes for Multi-Response Big Data With Qualitative Factors
Authors: Wang Liwei , Yerramilli Suraj , Iyer Akshay , Apley Daniel , Zhu Ping , Chen Wei
Published: November 2021

Scientific and engineering problems often require an inexpensive surrogate model to aid understanding and the search for promising designs. While Gaussian processes (GP) stand out as easy-to-use and interpretable learners in surrogate modeling, they have difficulties in accommodating big datasets, qualitative inputs, and multi-type responses obtained from different simulators, which has become a common challenge for a growing number of data-driven design applications. In this paper, we propose a GP model that utilizes latent variables and functions obtained through variational inference to address the aforementioned challenges simultaneously. The method is built upon the latent variable Gaussian process (LVGP) model where qualitative factors are mapped into a continuous latent space to enable GP modeling of mixed-variable datasets. By extending variational inference to LVGP models, the large training dataset is replaced by a small set of inducing points to address the scalability issue. Output response vectors are represented by a linear combination of independent latent functions, forming a flexible kernel structure to handle multi-type responses. Comparative studies demonstrate that the proposed method scales well for large datasets with over 104 data points, while outperforming state-of-the-art machine learning methods without requiring much hyperparameter tuning. In addition, an interpretable latent space is obtained to draw insights into the effect of qualitative factors, such as those associated with “building blocks” of architectures and element choices in metamaterial and materials design. Our approach is demonstrated for machine learning of ternary oxide materials and topology optimization of a multiscale compliant mechanism with aperiodic microstructures and multiple materials.
Feedback Control of the Locomotion of a Tailed Quadruped Robot
Authors: Liu Yujiong , Ben-Tzvi Pinhas
Published: November 2021

The traditional locomotion paradigm of quadruped robots is to use dexterous (multi degrees of freedom) legs and dynamically optimized footholds to balance the body and achieve stable locomotion. With the introduction of a robotic tail, a new locomotion paradigm becomes possible as the balancing is achieved by the tail and the legs are only responsible for propulsion. Since the burden on the leg is reduced, leg complexity can be also reduced. This paper explores this new paradigm by tackling the dynamic locomotion control problem of a reduced complexity quadruped (RCQ) with a pendulum tail. For this specific control task, a new control strategy is proposed in a manner that the legs are planned to execute the open-loop gait motion in advance, while the tail is controlled in a closed-loop to prepare the quadruped body in the desired orientation. With these two parts working cooperatively, the quadruped achieves dynamic locomotion. Partial feedback linearization (PFL) controller is used for the closed-loop tail control. Pronking, bounding, and maneuvering are tested to evaluate the controller’s performance. The results validate the proposed controller and demonstrate the feasibility and potential of the new locomotion paradigm.
Analysis of the Knowledge Gain and Cognitive Load Experienced Due to the Computer-Aided Instruction of Additive Manufacturing Processes
Authors: Mathur Jayant , Miller Scarlett R. , Simpson Timothy W. , Meisel Nicholas A.
Published: November 2021

Although there is a substantial growth in the Additive Manufacturing (AM) market commensurate with the demand for products produced by AM methods, there is a shortage of skilled designers in the workforce that can apply AM effectively to meet this demand. This is due to the innate complications with cost and infrastructure for high-barrier-to-entry AM processes such as powder bed fusion when attempting to educate designers about these processes through in-person learning. To meet the demands for a skilled AM workforce while also accounting for the limited access to the range of AM processes, it is important to explore other mediums of AM education such as computer-aided instruction (CAI) which can increase access to hands-on learning experiences. Therefore, the purpose of this paper is to analyze the use of CAI in AM process education and focus on its effects on knowledge gain and cognitive load. Our findings show that when designers are educated about material extrusion and powder bed fusion through CAI, the knowledge gain for powder bed fusion is significantly different than knowledge gain for material extrusion, with no significant difference in cognitive load between these two AM processes. These findings imply that there is potential in virtual mediums to improve a designer’s process-centric knowledge for the full range of AM processes including those that are usually inaccessible. We take these findings to begin developing recommendations and guidelines for the use of virtual mediums in AM education and future research that investigates implications for virtual AM education.
BIKED: A Dataset and Machine Learning Benchmarks for Data-Driven Bicycle Design
Authors: Regenwetter Lyle , Curry Brent , Ahmed Faez
Published: November 2021

In this paper, we present “BIKED,” a dataset comprised of 4500 individually designed bicycle models sourced from hundreds of designers. We expect BIKED to enable a variety of data-driven design applications for bicycles and support the development of data-driven design methods. The dataset is comprised of a variety of design information including assembly images, component images, numerical design parameters, and class labels. In this paper, we first discuss the processing of the dataset, then highlight some prominent research questions that BIKED can help address. Of these questions, we further explore the following in detail: 1) Are there prominent gaps in the current bicycle market and design space? We explore the design space using unsupervised dimensionality reduction methods. 2) How does one identify the class of a bicycle and what factors play a key role in defining it? We address the bicycle classification task by training a multitude of classifiers using different forms of design data and identifying parameters of particular significance through permutation-based interpretability analysis. 3) How does one synthesize new bicycles using different representation methods? We consider numerous machine learning methods to generate new bicycle models as well as interpolate between and extrapolate from existing models using Variational Autoencoders. The dataset is available at http://decode.mit.edu/projects/biked/ along with referenced code.
Investigating Mind-Mapping as a Tool for Problem Exploration in Early Design
Authors: Chen Ting-Ju , Vyas Shantanu , Krishnamurthy Vinayak R.
Published: November 2021

We present an experiment to study the role of mind-mapping as a tool for design opportunity identification and problem understanding. Our goal is to investigate how the quality of design opportunity statements change with two different techniques, namely, mind-mapping and free writing. Identifying design opportunities is an important step in new product development and little is currently understood in terms of what tools can provide cognitive support for problem clarification. In this work, we focus on mind-mapping as one example of a potential tool for providing such support. Mind-maps are well-known for their ability to enable the exploration of ideas in an unconstrained and structured way. To study their role in helping problem exploration, we conducted a between-subject user study with 28 participants to investigate how information structure and organization affect the exploration of ideas in a given design context. Further, we propose new evaluation metrics to quantitatively assess key elements presented in the design opportunity statements generated after exploring the problem domain. We report on the quantitative results, the exploration behaviors, and the general user feedback about the experience. Finally, we discuss the implications of these findings on design problem identification and future digital mind-mapping tools for exploratory tasks.
A Framework for Interactive Structural Design Exploration
Authors: Valdez Sofia , Seepersad Carolyn , Kambampati Sandilya
Published: November 2021

Rapid advances in additive manufacturing and topology optimization enable unprecedented levels of design freedom for realizing complex structures. The challenge is that the increasing design freedom is accompanied by increasing complexity, such that it can become difficult for either computational algorithms or human designers alone to search these expansive design spaces effectively. Our goal is to establish an interactive design framework that is both data-driven and designer-guided so that human designers can work together with computational algorithms to search structural design spaces more effectively. The framework builds upon classical topology optimization techniques to build a library of designs for a class of problems. A conditional generative adversarial network (cGAN) is trained to establish a latent representation of the library and to support rapid exploration of candidate designs. The library of designs is clustered based on visual similarity. The user selects clusters with desirable features, and the underlying latent representation is manipulated to generate visually similar candidate designs with adjustable levels of diversity or similarity to the selected clusters. The framework enables designers to use their expertise and intuition to guide the algorithm towards promising solutions by screening designs quickly and eliminating clusters of designs that may not be desirable for reasons that are difficult to embed within the optimization itself but are recognizable and significant to a human designer (e.g., secondary functionality, aesthetics).
A Blockchain-Enabled Approach for Online Stream Sensor Data Protection in Cyber-Physical Manufacturing Systems
Authors: Shi Zhangyue , Liu Chenang , Kan Chen , Tian Wenmeng , Chen Yang
Published: November 2021

With the rapid development of the Internet of Things and information technologies, more and more manufacturing systems become cyber-enabled, which significantly improves the flexibility and productivity of manufacturing. Furthermore, a large variety of online sensors are also commonly incorporated in the manufacturing systems for online quality monitoring and control. However, the cyber-enabled environment may pose the collected online stream sensor data under high risks of cyber-physical attacks as well. Specifically, cyber-physical attacks could occur during the manufacturing process to maliciously tamper the sensor data, which could result in false alarms or failures of anomaly detection. In addition, the cyber-physical attacks may also illegally access the collected data without authorization and cause leakage of key information. Therefore, it becomes critical to develop an effective approach to protect online stream data from these attacks so that the cyber-physical security of the manufacturing systems could be assured. To achieve this goal, an integrative blockchain-enabled method, is proposed by leveraging both asymmetry encryption and camouflage techniques. A real-world case study that protects cyber-physical security of collected stream data in additive manufacturing is provided to demonstrate the effectiveness of the proposed method. The results demonstrate that malicious tampering could be detected in a relatively short time and the risk of unauthorized data access is significantly reduced as well.
Identifying Computer-Aided Design Action Types From Professional User Analytics Data
Authors: Leonardo Kevin , Olechowski Alison
Published: November 2021

Inspired by popular personality type indicators, we develop a framework for classifying individuals by their computer-aided design (CAD) behaviours. We are motivated by the trend of modern CAD software towards cloud platforms and expanded collaborative features. Cloud-CAD platforms enable collaboration by increasing access, and reducing conflicts and barriers to file-sharing.

In order to generate insight to support CAD collaboration, we analyze the real-world data from an industry partner’s product development project, consisting of eight professional designers working on a cloud-CAD platform. This data corresponds to more than 1,420,000 actions over a span of eight months. Via hierarchical clustering, we group 79 unique CAD activities into 14 categories of CAD action groups, such as Part Studio, Assembly, Comment, View/Scan and Export. Next, we identify the degree to which each of the eight designers performs activity in these CAD action groups. We demonstrate the usefulness of this framework by highlighting insights revealed by the CAD action group mapping, confirmed via discussion with the industry partner. This CAD-type behaviour framework provides a tool for assessment and reflection on the types of behavioural tendencies present or missing on a team of designers. It can assist CAD educators and trainees in understanding their comprehensive CAD learning trajectory. Future extensions of the framework could leverage artificial intelligence techniques to provide real-time feedback on designer roles.
Development of a Design for Additive Manufacturing Worksheet for Medical Casts
Authors: Noh Heena , Park Kijung , Park Kiwon , Okudan Kremer Gül E.
Published: November 2021

Traditional plaster casts often cause dermatitis due to disadvantages in usability and wearability. Additive manufacturing (AM) can fabricate customized casts to have light-weight, high strength, and better air permeability. Although existing studies have provided design for additive manufacturing (DfAM) guidelines to facilitate design applications for AM, most relevant studies focused on the mechanical properties of outputs and too general/specific design guidelines; novice designers may still have difficulty understanding trade-offs between functional and operational performance of various DfAM aspects for medical casts. As a response, this study proposes a DfAM worksheet for medical casts to effectively guide novice designers. First, important DfAM criteria and their possible solutions for medical casts are examined through a literature review to construct a basic DfAM framework for medical casts. Next, a scoring system that considers relative criteria importance and criteria evaluation from both functional and operational perspectives is developed to identify the overall suitability of a medical cast design for AM. A case study of finger cast designs was performed to identify the DfAM performance of the sample designs along with redesign requirements suggested by the worksheet. The proposed worksheet would be used to achieve rapid medical cast design by objectively assessing its suitability for AM.
Multibody Models for Tower Vibrations With an Unbalanced Rotor
Authors: Pedersen Simon S. , Madsen Niclas B. , Escalona José L. , Balling Ole
Published: November 2021

This paper compares different models that can be used to analyze the vibrations of an unbalanced rotor with horizontal axis over a flexible tower. Model results are compared with experimental results. The modeled system is equivalent to a wind turbine with perfectly rigid blades. The selected models are the linear elastic model that is obtained using the linear theory of vibrations and two multibody models. The first multibody model uses Component Mode Synthesis for the description of the tower flexibility while the second multibody model used a lumped properties approach. Experimental results validate with reasonable agreement the resonance speeds of an unbalanced rotor. Furthermore, the models, while low degrees of freedom, give valuable insight of inertial loads on drivetrain components based on tower top dynamic motion. The work presented in this paper showed the use of 3 low-degrees of freedom models to predict resonance and tower top displacements. All simulation models did exhibit slightly higher resonance frequencies than the experimental results. The results showed that the tower top motion for the rectangular tower resembles a figure eight type motion, while the square tower top shows an elliptical motion.
Quantitative mental state attributions in language understanding
Authors: Jara-Ettinger Julian , Rubio-Fernandez Paula
Published: November 2021

People can build nuanced and accurate representations of the contents of other people’s minds based on how they speak.
Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation
Authors: Oda Yukako , Takahashi Chisato , Harada Shota , Nakamura Shun , Sun Daxiao , Kiso Kazumi , Urata Yuko , Miyachi Hitoshi , Fujiyoshi Yoshinori , Honigmann Alf , Uchida Seiichi , Ishihama Yasushi , Toyoshima Fumiko
Published: November 2021

C-terminal alpha 1-antitrypsin peptides induce tight junction formation by activating G protein G13.
Genus-Specific Carbon Fixation Activity Measurements Reveal Distinct Responses to Oxygen among Hydrothermal VentCampylobacteria
Authors: McNichol Jesse , Dyksma Stefan , Mußmann Marc , Seewald Jeffrey S. , Sylva Sean P. , Sievert Stefan M.
Published: November 2021

Sulfidic environments worldwide are often dominated by sulfur-oxidizing, carbon-fixingCampylobacteria. Environmental factors associated with this group’s dominance are now understood, but far less is known about the ecology and physiology of members of subgroups of chemoautotrophicCampylobacteria.
Evaluation of the MRSA/SA ELITe MGB Assay for the Detection of
Staphylococcus aureus
in Bone and Joint Infections
Authors: Labetoulle R. , Rigaill J. , Lleres-Vadeboin M. , Grattard F. , Pozzetto B. , Cazorla C. , Botelho-Nevers E. , Boyer B. , Dupieux-Chabert C. , Laurent F. , Verhoeven P. O. , Carricajo A.
Published: November 2021

Bone and joint infections represent a potentially devastating complication of prosthetic orthopedic joint replacement, thus requiring both rapid and appropriate antibiotic treatment.
Staphylococcus aureus
is one of the most common pathogens involved in this pathology. Being able to assert its presence is the first step of efficient patient management.
The Combined Expression of the Nonstructural Protein NS1 and the N-Terminal Half of NS2 (NS2
1-180
) by ChAdOx1 and MVA Confers Protection against Clinical Disease in Sheep upon Bluetongue Virus Challenge
Authors: Utrilla-Trigo Sergio , Jiménez-Cabello Luis , Calvo-Pinilla Eva , Marín-López Alejandro , Lorenzo Gema , Sánchez-Cordón Pedro , Moreno Sandra , Benavides Julio , Gilbert Sarah , Nogales Aitor , Ortego Javier
Published: November 2021

Current BTV vaccines are effective but they do not allow to distinguish between vaccinated and infected animals (DIVA strategy) and are serotype specific. In this work we have develop a DIVA multiserotype vaccination strategy based on adenoviral (ChAdOx1) and MVA vaccine vectors, the most widely used in current phase I and II clinical trials, and the conserved nonstructural BTV proteins NS1 and NS2. This immunization strategy solves the major drawbacks of the current marketed vaccines.
Fracture in an arthrodesed Charcot’s knee joint
Authors: Reddy Sai Sabharish , Vaish Abhishek , Vaishya Raju
Published: November 2021

Charcot’s joint is a type of neuro-arthropathy, where asymmetrical damage of the involved joint happens haphazardly, without following any described pattern. We present a rare case of Charcot’s joint involving the knee joint in an adult male following spina bifida. His knee joint was successfully fused after two surgeries. Later, he sustained a fracture through the arthrodesis after a fall, which we managed surgically. The fracture through the knee arthrodesis was managed surgically by an open reduction and internal fixation, using a 14-hole broad low contact dynamic compression locking plate with bone grafting. Union was achieved at the knee arthrodesis site in 6 months. Fracture through a fused knee requires surgical management. Re-arthrodesis was done using a stable fixation. Postoperative rehabilitation should include protected weight bearing with braces and splints until a sound bony union is achieved.
Activated but impaired IFN-γ production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma
Authors: Huang Wenyong , Ye Dongmei , He Wenjing , He Xiaoshun , Shi Xiaomin , Gao Yifang
Published: November 2021

Objective

Mucosal-associated invariant T (MAIT) cells are innate T cells with immunoregulatory activity and were recently found to be associated with various tumor types. The role of intrasinusoidal MAIT cells in hepatocellular carcinoma (HCC) has not been fully characterized.

Design

Peripheral blood samples were obtained from patients with HCC and healthy controls. Liver-associated mononuclear cells (LMCs) were collected from liver perfusions of donors and patients with HCC undergoing liver transplantation. Blood and liver perfusates from patients with HCC were analyzed by flow cytometry for CD3 +CD161+Vα7.2+MAIT cell frequency, phenotype, and function.

Results

There were fewer MAIT cells in the peripheral blood and liver of patients with HCC than in the healthy controls. Interferon-γ (IFN-γ) production by these cells was also reduced. Peripheral MAIT cells showed upregulation of HLA-DR (Human Leukocyte Antigen DR） and the inhibitory molecule PD-1 (Programmed Cell Death Protein 1), but no significant differences in upregulation were found in intrasinusoidal MAIT cells. MAIT cells were significantly enriched in the liver relative to that in the peripheral blood of patients with HCC. High levels of activation markers and exhaustion markers including HLA-DR, CD69, and PD-1 were observed in LMCs of patients with HCC but not in the peripheral blood. Single-cell RNA sequencing revealed that intrasinusoidal MAIT cells exhibited distinct features in patients with HCC and the controls.

Conclusion

Our study showed that alterations in MAIT cells are associated with HCC. The distinct activity and function of MAIT cells in the peripheral blood and liver of patients with HCC might suggest a potential role of these cells in disease pathogenesis.
Geochronology, geochemistry, Sr–Nd–Hf isotope composition of the late Permian adakite in West Ujimqin, Inner Mongolia: petrogenesis and tectonic implications
Authors: Fan Yuxu , Xiao Qinghui , Li Tingdong , Cheng Yang , Li Yan , Guo Lingjun , Luo Pengyue
Published: November 2021

We report herein on new zircon U–Pb ages, the major and trace elements of whole-rock, and the Sr–Nd–Hf isotope composition for adakitic intrusives collected from the West Ujimqin district in the Southeast region of the Central Asian Orogenic Belt (CAOB). These data provide important constraints on the petrogenetic evolution and geodynamic setting of late Permian magmatism in the Southeast CAOB. The U–Pb dating of zircon shows that the ages of Seerbeng pluton and Nuhetingshala pluton in West Ujimqin are 255.3 ± 0.71 and 254.4 ± 1.2 Ma, respectively, which signifies that these are products of magmatic activity in the late Permian. The adakitic intrusives are characterized by high levels of Sr (Sr ≥ 741 ppm), low Y, low Yb, high Sr:Y ratios, and strongly fractionated rare earth elements (10.3 < LaN/YbN < 22.5), which is similar to the features of the adakite. The magmatic zircons exhibit positive Hf values (+8.1 to +13.3), and young two-stage model ages vary from 430 to 760 Ma. The high εNd(t) and low (87Sr:86Sr)i indicate that the adakitic granite derived from the partial melting of subducted oceanic slab. The high level of Mg# [100 × Mg/(Mg + Fe) in atomic number] and abundant Cr–Ni indicate that magmatic melts interacted with olivine rocks in the mantle. Considering these results and the regional rock assemblies, we conclude that the Paleo-Asian Ocean had not yet completely closed in the late Permian, and northward subduction continued, with the subducted slab possibly breaking off.
False biosignatures on Mars: anticipating ambiguity
Authors: McMahon Sean , Cosmidis Julie
Published: November 2021

It is often acknowledged that the search for life on Mars might produce false positive results, particularly via the detection of objects, patterns or substances that resemble the products of life in some way but are not biogenic. The success of major current and forthcoming rover missions now calls for significant efforts to mitigate this risk. Here, we review known processes that could have generated false biosignatures on early Mars. These examples are known largely from serendipitous discoveries rather than systematic research and remain poorly understood; they probably represent only a small subset of relevant phenomena. These phenomena tend to be driven by kinetic processes far from thermodynamic equilibrium, often in the presence of liquid water and organic matter, conditions similar to those that can actually give rise to, and support, life. We propose that strategies for assessing candidate biosignatures on Mars could be improved by new knowledge on the physics and chemistry of abiotic self-organization in geological systems. We conclude by calling for new interdisciplinary research to determine how false biosignatures may arise, focusing on geological materials, conditions and spatiotemporal scales relevant to the detection of life on Mars, as well as the early Earth and other planetary bodies.

Thematic collection:
This article is part of the Astrobiology: Perspectives from the Geology of Earth and the Solar System collection available at:
https://www.lyellcollection.org/cc/astrobiology-perspectives-from-geology-of-earth-and-solar-system
Volcaniclastic lacustrine sedimentation in the Pleistocene Guayllabamba intermontane basin in the Ecuadorian Andes
Authors: Martin-Merino German , Roverato Matteo , Almeida Rafael
Published: November 2021

In this work, we present a description of the sedimentary fill of a well-exposed lacustrine succession in the Ecuadorian Andes. The Guayllabamba basin is an intermontane basin located in the Andean range of Ecuador, and part of its sedimentary history is represented by a volcanically influenced
c.
100 m-thick lacustrine unit of Pleistocene age. We create a stratigraphic cross-section from the eastern to western lake margins and identify 19 facies that were used to carry out a palaeoenvironmental reconstruction. The Guayllabamba palaeolake was developed in a tectonic depression surrounded by volcanoes and it was filled with sediments derived from the erosion of the volcanic edifices, the reworking of unconsolidated pyroclastic deposits and deposition of pyroclastic currents into the lake. The lake shows a deepening trend, passing from shallow deltaic sedimentation to varved diatomites with turbidites. Abundant ash-fall beds, monolithological pumiceous deltaic sequences and pumice-dominated thick ignimbrites show the impacts of volcanism on lacustrine sedimentation within this basin. Soft-sediment deformation and gravity flow deposits are common owing to the intrabasinal tectonic activity and to the intrusion of a lava body.
Aulacoseira
-rich diatomites dominate the background lake sedimentation. The outcrops of the Guayllabamba basin are outstanding examples of the interaction between volcaniclastic and lacustrine sedimentation.
Dual Gated Graph Attention Networks with Dynamic Iterative Training for Cross-Lingual Entity Alignment
Authors: Xie Zhiwen , Zhu Runjie , Zhao Kunsong , Liu Jin , Zhou Guangyou , Huang Jimmy Xiangji
Published: November 2021

Cross-lingual entity alignment has attracted considerable attention in recent years. Past studies using conventional approaches to match entities share the common problem of missing important structural information beyond entities in the modeling process. This allows graph neural network models to step in. Most existing graph neural network approaches model individual knowledge graphs (KGs) separately with a small amount of pre-aligned entities served as anchors to connect different KG embedding spaces. However, this characteristic can cause several major problems, including performance restraint due to the insufficiency of available seed alignments and ignorance of pre-aligned links that are useful in contextual information in-between nodes. In this article, we propose DuGa-DIT, a dual gated graph attention network with dynamic iterative training, to address these problems in a unified model. The DuGa-DIT model captures neighborhood and cross-KG alignment features by using intra-KG attention and cross-KG attention layers. With the dynamic iterative process, we can dynamically update the cross-KG attention score matrices, which enables our model to capture more cross-KG information. We conduct extensive experiments on two benchmark datasets and a case study in cross-lingual personalized search. Our experimental results demonstrate that DuGa-DIT outperforms state-of-the-art methods.
Skeletal muscle wasting: the estrogen side of sexual dimorphism
Authors: McMillin Shawna L. , Minchew Everett C. , Lowe Dawn A. , Spangenburg Espen E.
Published: November 2021

The importance of defining sex differences across various biological and physiological mechanisms is more pervasive now than it has been over the past 15–20 years. As the muscle biology field pushes to identify small molecules and interventions to prevent, attenuate, or even reverse muscle wasting, we must consider the effect of sex as a biological variable. It should not be assumed that a therapeutic will affect males and females with equal efficacy or equivalent target affinities under conditions where muscle wasting is observed. With that said, it is not surprising to find that we have an unclear or even a poor understanding of the effects of sex or sex hormones on muscle wasting conditions. Although recent investigations are beginning to establish experimental approaches that will allow investigators to assess the impact of sex-specific hormones on muscle wasting, the field still needs rigorous scientific tools that will allow the community to address critical hypotheses centered around sex hormones. The focus of this review is on female sex hormones, specifically estrogens, and the roles that these hormones and their receptors play in skeletal muscle wasting conditions. With the overall review goal of assembling the current knowledge in the area of sexual dimorphism driven by estrogens with an effort to provide insights to interested physiologists on necessary considerations when trying to assess models for potential sex differences in cellular and molecular mechanisms of muscle wasting.
Extracellular cysteines C226 and C232 mediate hydrogen sulfide-dependent inhibition of Orai3-mediated store-operated calcium entry
Authors: Fresquez Adriana M. , White Carl
Published: November 2021

The gaseous signaling molecule hydrogen sulfide (H2S) physiologically regulates store-operated Ca2+ entry (SOCE). The SOCE machinery consists of the plasma membrane-localized Orai channels (Orai1-3) and endoplasmic reticulum-localized stromal interaction molecule (STIM)1 and STIM2 proteins. H2S inhibits Orai3- but not Orai1- or Orai2-mediated SOCE. The current objective was to define the mechanism by which H2S selectively modifies Orai3. We measured SOCE and STIM1/Orai3 dynamics and interactions in HEK293 cells exogenously expressing fluorescently tagged human STIM1 and Orai3 in the presence and absence of the H2S donor GYY4137. Two cysteines (C226 and C232) are present in Orai3 that are absent in the Orai1 and Orai2. When we mutated either of these cysteines to serine, alone or in combination, SOCE inhibition by H2S was abolished. We also established that inhibition was dependent on an interaction with STIM1. To further define the effects of H2S on STIM1/Orai3 interaction, we performed a series of fluorescence recovery after photobleaching (FRAP), colocalization, and fluorescence resonance energy transfer (FRET) experiments. Treatment with H2S did not affect the mobility of Orai3 in the membrane, nor did it influence STIM1/Orai3 puncta formation or STIM1-Orai3 protein-protein interactions. These data support a model in which H2S modification of Orai3 at cysteines 226 and 232 limits SOCE evoked upon store depletion and STIM1 engagement, by a mechanism independent of the interaction between Orai3 and STIM1.
Herb-Partitioned Moxibustion Improves Crohn’s Disease-Associated Intestinal Fibrosis by Suppressing the RhoA/ROCK1/MLC Pathway
Authors: Zhao Min , Weng Zhijun , Huang Yan , Zheng Handan , Han Dong , Shen Jiacheng , Huang Rong , Liu Huirong , Wu Luyi
Published: November 2021

Background and Aims. Intestinal fibrosis is one of the severe and common complications of Crohn’s disease (CD), but the etiology and pathogenesis remain uncertain. The study intended to examine whether the effect of herb-partitioned moxibustion on rats with CD-associated intestinal fibrosis is associated with the RhoA/ROCK1/MLC pathway. Methods. All experimental rats were randomly allocated into the normal control group (NC), model control group (MC), and herb-partitioned moxibustion group (HPM). Intestinal fibrosis was established in rats with CD by repeated rectal administrations of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Herb-partitioned moxibustion was applied at the Qihai (CV6) and Tianshu (ST25) acupoints once daily for 10 days in the HPM group. In this study, histological changes were examined by hematoxylin and eosin (HE) staining; then, Masson’s trichrome staining was used to assess the degree of fibrosis in each group. Experimental methods of immunohistochemistry, western blotting, and real-time PCR were applied to detect the levels of α-SMA, collagen III, RhoA, ROCK1, and p-MLC. Moreover, the double immunofluorescent staining for the colocalization of both α-SMA and ROCK1 was performed. Results. Contrasted with the normal controls, the collagen deposition and fibrosis scores were increased in colonic tissue of model rats, and HPM decreased the collagen deposition and fibrosis scores. The protein of α-SMA and collagen III in the MC group exceeds that of the NC group; HPM decreased the expression of α-SMA and collagen III in rats with intestinal fibrosis. Similarly, the expression of RhoA, ROCK1, and p-MLC in model rats was obviously increased compared with normal controls; the expression of RhoA, ROCK1, and p-MLC was decreased after HPM. The coexpression of α-SMA and ROCK1 in rats with intestinal fibrosis was higher than normal rats. Conclusion. HPM improves CD-associated intestinal fibrosis by suppressing the RhoA/ROCK1/MLC pathway.
A Comparison Study of the Effect on IBS-D Rats among Ginger-Partitioned Moxibustion, Mild Moxibustion, and Laser Moxibustion
Authors: Sun Chao , Yang Xiaofeng , Xie Sirui , Zhou Ziqin , Yu Guoliang , Feng Shangsheng , Zhao Jingyu , Wu Jiangtao , Ji Changchun
Published: November 2021

Background. Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional gastrointestinal disorder that severely affects patients’ life. Moxibustion is believed to be an effective way to treat IBS-D. However, the therapeutic effects and the underlying mechanisms in symptom management of IBS-D by different moxibustion therapies remain unclear. Methods. IBS-D model rats were divided into groups and treated with ginger-partitioned moxibustion (GPM), mild moxibustion (MM), and laser moxibustion (LM) at a temperature of 43°C, respectively. The temperature curves of acupoints were recorded during interventions. The therapeutic effects were evaluated on the basis of general condition, stool, and hematoxylin-eosin staining of the colon tissue. Moreover, the expression of transient receptor potential vanilloid 1 (TRPV1) receptors in both acupoint tissue and colon tissue was analyzed by immunohistochemistry. Results. After moxibustion treatment, the symptoms were improved. The expression of TRPV1 was increased in acupoint tissue and decreased in colon tissue. GPM and MM showed a more significant influence on IBS-D rats compared with LM. The temperature profile of GPM and MM was wave-like, while LM had an almost stable temperature curve. Conclusion. GPM, MM, and LM could improve the symptoms in IBS-D rats. Moxibustion might activate TRPV1 channels in the acupoint tissue and induce acupoint functions, which in turn inhibit the pathological activation state of the colon’s TRPV1, followed by improvements in abdominal pain and diarrheal symptoms. LM with stable temperature might lead to the desensitization of TRPV1 receptors and the tolerance of acupoint. GPM and MM provided dynamic and repetitive thermal stimulations that perhaps induced acupoint sensitization to increase efficacy. Therefore, dynamic and repetitive thermal stimulation is recommended in the application of moxibustion.
Numerical Analysis of Thermal Environment in Deep Mining
Authors: Li Qi , You Shuang , Ji HongGuang , Xu Huici , Wang Huan
Published: November 2021

To analyze heat effect in deep metal mines, it is crucial to understand the temperature field distribution around the mine tunnel. In this paper, a numerical model of the random mineral composition of the rock body is established based on finite element software to analyze the influence of the internal composition of the surrounding rock on the temperature field, and a numerical simulation model based on COMSOL finite element software is established based on the two heat exchange modes of heat conduction and heat convection in the surrounding rock. The results show that the numerical simulation results of a typical numerical simulation model using a single material are lower than the real situation; increasing the tunnel length does not increase the heat exchange efficiency between the rock wall and the air; increasing the wind velocity has a limited impact on the temperature field; the wind temperature more directly affects the mining surface; and the effect of wet air on the temperature field of the surrounding rock has a more substantial variation.
Lessons Learned from a Small Pediatric Continuous Renal Replacement Therapy Program
Authors: Holt Tanya , Griffin Olivia , Cyr Amelie , Brockman Rebecca , Wihak Laura , Hansen Gregory
Published: November 2021

Continuous renal replacement therapy (CRRT) has become a pillar of care in pediatric intensive care units (PICUs) over the past few decades. Quality indicators (QIs) have been evaluated that reflect safe and accountable CRRT. However, there is a paucity of data on outcomes and QIs in smaller-volume CRRT programming. The purpose of this retrospective study was to evaluate the efficiencies, effectiveness, and outcomes of a small-volume CRRT program. Eighty-two patients received CRRT over a 13-year period, and 79% survived to discharge. Sepsis or nonseptic shock (n = 11 (22%) versus n = 6 (50%);

p

value = 0.004) and time to CRRT initiation after PICU admission (1.1 versus 5.0 days;

p

value = 0.005) were independent predictors for mortality. The program also had positive outcomes for QIs related to CRRT efficiency and time of initiation, dosing delivery, and rate of adverse events. This study is important as it illustrates the opportunity that smaller centers have to initiate CRRT programming and provide safe and effective care.
Analyzing the Physical and Mental Quality of College Students Using Multidimensional Data Mining
Authors: Mu Yuanhong
Published: November 2021

Shaping the healthy psychology of college students and promoting the healthy growth of talents are the goals that colleges and universities should strive for in moral education. The mobile Internet era has brought opportunities and challenges to the psychological quality education of college students. In order to effectively cope with the existing challenges, it is imperative to explore a psychological quality education model that conforms to the new environment. Therefore, this article has carried out the analysis and management of the physical and mental quality of college students based on multidimensional data mining. By adopting exploratory factor analysis and confirmatory factor analysis methods, this paper establishes a structural equation model of students’ psychological quality. Through the theoretical discussion of psychological quality, the connotation and characteristics of the psychological quality of college students are further defined. We should discuss the relationship between psychological quality and other psychological phenomena and provide suggestions for college students’ psychological quality. There is a need for an empirical research program for the quality structure and actual psychological quality structure. Finally, we conducted a multidimensional evaluation of the program through the TOPSIS evaluation model and confirmed the effectiveness of the program.
Selection of an Inert Gas System for the Transportation of Direct Reduced Iron
Authors: Yazir Devran , Sahin Bekir , Alkac Murat
Published: November 2021

Direct reduced iron (DRI) can create significant risks such as ignition, explosion, and fire because of the oxidation reaction in case when DRI undergoes spontaneously heating and comes in contact with oxygen or water. For this reason, the transportation of DRI is classified as a dangerous task of which the inert process should be done in the ship’s holds. Many studies have been conducted on the production and production stages of DRI and other areas of use of inert gas, but no studies have been conducted on the safe transportation of this cargo by ships. This study analyzes the criteria and alternatives for selecting the inert gas system for the benefits of investors and shipowners in the shipping industry. The intuitionistic fuzzy TOPSIS (IF-TOPSIS) method is implemented to conduct the decision-making process. As a result of this study, preferences for candidate inert gas systems are modelled. Port facility nitrogen generator is selected as the most suitable inert gas system among alternative inert gas systems based on predetermined criteria.
Keratoconus Severity Classification Using Features Selection and Machine Learning Algorithms
Authors: Aatila Mustapha , Lachgar Mohamed , Hamid Hrimech , Kartit Ali
Published: November 2021

Keratoconus is a noninflammatory disease characterized by thinning and bulging of the cornea, generally appearing during adolescence and slowly progressing, causing vision impairment. However, the detection of keratoconus remains difficult in the early stages of the disease because the patient does not feel any pain. Therefore, the development of a method for detecting this disease based on machine and deep learning methods is necessary for early detection in order to provide the appropriate treatment as early as possible to patients. Thus, the objective of this work is to determine the most relevant parameters with respect to the different classifiers used for keratoconus classification based on the keratoconus dataset of Harvard Dataverse. A total of 446 parameters are analyzed out of 3162 observations by 11 different feature selection algorithms. Obtained results showed that sequential forward selection (SFS) method provided a subset of 10 most relevant variables, thus, generating the highest classification performance by the application of random forest (RF) classifier, with an accuracy of 98% and 95% considering 2 and 4 keratoconus classes, respectively. Found classification accuracy applying RF classifier on the selected variables using SFS method achieves the accuracy obtained using all features of the original dataset.
Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer
Authors: Grossman Joseph E. , Muthuswamy Lakshmi , Huang Ling , Akshinthala Dipikaa , Perea Sofia , Gonzalez Raul S. , Tsai Leo L. , Cohen Jonah , Bockorny Bruno , Bullock Andrea J. , Schlechter Benjamin , Peters Mary Linton B. , Conahan Catherine , Narasimhan Supraja , Lim Christine , Davis Roger B. , Besaw Robert , Sawhney Mandeep S. , Pleskow Douglas , Berzin Tyler M. , Smith Martin , Kent Tara S. , Callery Mark , Muthuswamy Senthil K. , Hidalgo Manuel
Published: November 2021

Purpose:

Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes.

Experimental Design:

PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes.

Results:

A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients.

Conclusions:

These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.
Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice
Authors: Le Xiuning , Sakai Hiroshi , Felip Enriqueta , Veillon Remi , Garassino Marina Chiara , Raskin Jo , Cortot Alexis B. , Viteri Santiago , Mazieres Julien , Smit Egbert F. , Thomas Michael , Iams Wade T. , Cho Byoung Chul , Kim Hye Ryun , Yang James Chih-Hsin , Chen Yuh-Min , Patel Jyoti D. , Bestvina Christine M. , Park Keunchil , Griesinger Frank , Johnson Melissa , Gottfried Maya , Britschgi Christian , Heymach John , Sikoglu Elif , Berghoff Karin , Schumacher Karl-Maria , Bruns Rolf , Otto Gordon , Paik Paul K.
Published: November 2021

Purpose:

Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups.

Patients and Methods:

This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity.

Results:

152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7–53.0]. Patients aged <75 (n = 84) and ≥75 (n = 68) had ORRs of 48.8% (95% CI: 37.7–60.0) and 39.7% (95% CI: 28.0–52.3), respectively. Treatment-naïve (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9–57.4) vs. 44.6% (33.7–55.9); median duration of response (95% CI): 10.8 (6.9–not estimable) vs. 11.1 (9.5–18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies.

Conclusions:

Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations.

See related commentary by Rosner and Spira, p. 1055