Miracle-dz/UniFAR-FTUs huggingface dataset:
Cryo-EM structure of the full-length WzmWzt ABC transporter required for lipid-linked O antigen transport

Significance Gram-negative bacteria employ cell surface polysaccharides to evade host immune responses, enhance survival in extreme environments, and protect themselves against antimicrobial agents. The outer membrane of gram-negatives is rich in lipopolysaccharide (LPS), comprising the endotoxin lipid A, a short oligosaccharide, and a long terminal polysaccharide known as the O antigen. O antigens extend the cellular envelope creating a barrier that obscures the cell membrane to protect it from complement component deposition and insertion, thereby evading the innate immune response of the host. Understanding O antigen biosynthesis and how the specialized ABC transporter WzmWzt translocates the O antigen for assembly of mature LPS provides a molecular basis for manipulating this fundamental process in gram-negative pathogens. O antigens are important cell surface polysaccharides in gram-negative bacteria where they extend core lipopolysaccharides in the extracellular leaflet of the outer membrane. O antigen structures are serotype specific and form extended cell surface barriers endowing many pathogens with survival benefits. In the ABC transporter-dependent biosynthesis pathway, O antigens are assembled on the cytosolic side of the inner membrane on a lipid anchor and reoriented to the periplasmic leaflet by the channel-forming WzmWzt ABC transporter for ligation to the core lipopolysaccharides. In many cases, this process depends on the chemical modification of the O antigen’s nonreducing terminus, sensed by WzmWzt via a carbohydrate-binding domain (CBD) that extends its nucleotide-binding domain (NBD). Here, we provide the cryo-electron microscopy structure of the full-length WzmWzt transporter from Aquifex aeolicus bound to adenosine triphosphate (ATP) and in a lipid environment, revealing a highly asymmetric transporter organization. The CBDs dimerize and associate with only one NBD. Conserved loops at the CBD dimer interface straddle a conserved peripheral NBD helix. The CBD dimer is oriented perpendicularly to the NBDs and its putative ligand-binding sites face the transporter to likely modulate ATPase activity upon O antigen binding. Further, our structure reveals a closed WzmWzt conformation in which an aromatic belt near the periplasmic channel exit seals the transporter in a resting, ATP-bound state. The sealed transmembrane channel is asymmetric, with one open and one closed cytosolic and periplasmic portal. The structure provides important insights into O antigen recruitment to and translocation by WzmWzt and related ABC transporters.
A multiple case study of coordinated care for children with IBD through caregiver interviews

Introduction Effective care coordination is critical to manage unpredictable complications of conditions such as pediatric inflammatory bowel disease (IBD) that have a relapsing and remitting course. Our objective was to explore perspectives of care coordination following emergency department (ED) visits by children with IBD, because these may indicate deficient care coordination. Methods Using a multiple case study approach, we sought perspectives through semi-structured interviews of caregivers (parents, primary care providers, and gastroenterologists) for children with IBD who had a recent ED visit in either of two large pediatric referral centers in the southeastern US. We used criterion sampling to identify eligible participants through a medical record report of ED visits, and iterative sampling concurrent with analysis until no new themes were identified. Interviews were transcribed verbatim, and transcripts were coded using directed content analysis to identify emergent themes. Results From twenty-six interviews, three major themes emerged: perceptions of appropriate expertise, desire for integration of information and services, and making assumptions instead of engaging. Participants describe distinct roles for primary care and gastroenterology providers and recognize communication and information barriers to better coordination. Some parents and gastroenterologists perceive challenges to engaging primary care providers. Common recommendations include explicit guidance from gastroenterologists to primary care providers and methods for direct communication. Discussion Stakeholders describe common barriers and facilitators for effective care coordination, but some express beliefs about provider roles that could hinder improvement efforts. Tools to support asynchronous communication and shared planning may improve coordination and care quality for complications of IBD.
Home Automation System Using IoT and Machine Learning Techniques

For maintaining comfortable living conditions within a home, Home Automation can be used. Least interaction with the system makes the system easy to use and uncomplicated. ​Faces can be used as the key to the room for automation of the devices and peripherals. When the person walks into the room the devices preselected turn on without having the user press any buttons inside the room to switch them on. Users can preselect what devices users want to be switched on during the process. Users need to train their faces to be recognized. Different users can register for unique personalization. This system represents the application of IoT for Home Automation system using smart techniques which includes a Raspberry Pi as a processing unit for data which is extracted from camera and a Graphical User Interface for program control.
Productivity, Sustainability, and Economic Growth in Metropolises: Estimates of Long-Time Commuting Effects in Developing Countries

In this study, the long-time commuting patterns of workers in six of the biggest metropolises of the world were observed â€“ New Delhi, Mexico City, SA£o Paulo, Manilla, Nairobi, and Accra â€“ located in very different geographic regions, and all of them coming from the developing world. The main question to be answered was whether there is scope for labor policy changes towards productivity improvements in this area. The findings brought fundamental insights to the debate about big cities' problems to avoid becoming more crowded, congested, and polluted, reducing sustainability, productivity, and economic growth. Simple random samples of workers in the Metropolitan Areas of each city were surveyed electronically, by Google-Forms e-survey during the second half of 2019. The sample proportions were the estimators of the population proportions. Considering specific error margins â€“ below 5 percentage points â€“ for each city, and with a 95 percent point of confidence level, the authors used proportion sample distributions to draw inferences about the population of workers. It was found that long-time commuters are between 12 and 26 percent of the workers who participated in the survey. More than 65 percent of workers in all the cities observed were interested in reducing commuting time. More than half of the workers agreed that reducing commuting time could improve labor productivity, and approximately the same share is aware of the negative effects on quality of life and health. Labor policy changes in these six metropolises have the potential of affecting more than 6.5 million workers.
OWNERSHIP OF DUAL CLASS SHARES AND PASSIVE INVESTMENT STRATEGIES

Previous studies of firms with two classes of stock find a price premium for the class with superior voting rights over the restricted voting rights shares. This premium changes over time and is related to the likelihood of a contested takeover attempt. These findings have implications for both passive and active investors. We find that for passive, buy-and-hold investors, restricted voting shares dominate superior voting shares in mean-variance space. This relationship also holds for a four factor model specification of stock returns. Our evidence indicates that passive, buy-and-hold investors can achieve a higher return with restricted vote shares than superior vote shares with no increase in either standalone or portfolio risk. * Corresponding author:, Fayetteville State University, 1200 Murchison Road, Fayetteville, NC 28301, Phone: (910) 672-1736 Fax: (910) 672-2065, Email: tgewilliams@uncfsu.edu
Synthesis of the 6-Substituted Imidazo[1,2-a]Pyridine-3-yl-2- Phosphonopropionic Acids as Potential Inhibitors of Rab Geranylgeranyl Transferase

Twelve phosphonopropionates derived from 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid (3-IPEHPC) were synthesized and evaluated for their activity as inhibitors of protein geranylgeranylation. The nature of the substituent in the C6 position of imidazo[1,2-a]pyridine ring was responsible for the compound's activity against Rab geranylgeranyl transferase (RGGT). The most active inhibitors disrupted Rab11A prenylation in the human cervical carcinoma HeLa cell line. The esterification of carboxylic acid in the phosphonopropionate moiety turned the inhibitor into an inactive analog.
WGEVIA: A Graph Level Embedding Method for Microcircuit Data

Functional microcircuits are useful for studying interactions among neural dynamics of neighboring neurons during cognition and emotion. A functional microcircuit is a group of neurons that are spatially close, and that exhibit synchronized neural activities. For computational analysis, functional microcircuits are represented by graphs, which pose special challenges when applied as input to machine learning algorithms. Graph embedding, which involves the conversion of graph data into low dimensional vector spaces, is a general method for addressing these challenges. In this paper, we discuss limitations of conventional graph embedding methods that make them ill-suited to the study of functional microcircuits. We then develop a novel graph embedding framework, called Weighted Graph Embedding with Vertex Identity Awareness (WGEVIA), that overcomes these limitations. Additionally, we introduce a dataset, called the five vertices dataset, that helps in assessing how well graph embedding methods are suited to functional microcircuit analysis. We demonstrate the utility of WGEVIA through extensive experiments involving real and simulated microcircuit data.
Chemical Characteristics of Three Kinds of Japanese Soy Sauce Based on Electronic Senses and GC-MS Analyses

Japanese soy sauce has become more acceptable by Chinese consumers due to its umami taste. However, the volatile flavor compounds and taste characters have not been fully clarified. This study aimed to explore the flavor characteristics of three kinds of Japanese soy sauce, including Koikuchi Shoyu, Usukuchi Shoyu, and Amakuchi Shoyu. The secret of volatile flavor substances was investigated by Gas Chromatography-Mass Spectrometry (GC-MS) and electronic nose, while taste compounds were investigated by silylation GC-MS and electronic tongue (E-tongue). A total of 173 volatile flavor substances and 160 taste compounds were identified. In addition, 28 aroma compounds with odor activity values (OAV) ≥ 1 were considered as the typical flavors. We found that alcohols and aldehydes were in high abundance in Japanese soy sauce, but only a small portion of pyrazines and esters were. Based on electronic nose and GC-MS analysis, Koikuchi Shoyu gives more contribution to aroma compounds, while Usukuchi Shoyu and Amakuchi Shoyu give the sourness and sweetness features based on E-tongue and silylation GC-MS analysis. In this study, 50 kinds of sugars were detected that contributed to the sweetness of soy sauce. This study will provide new insight into the flavor characteristics of Japanese soy sauce that potentially contribute to the innovation and development of soy sauce.
Testing a cultural orientation model of electronic word-of-mouth communication: a comparative study of U.S. and Korean social media users

ABSTRACT Expanding electronic word-of-mouth (eWOM) literature and cross-cultural literature, this study proposes a horizontal–vertical dimensions of individualism and collectivism (HVIC)-eWOM model in a cross-cultural context. We employed HVIC at the individual level to explain the variance of eWOM communications on social media. We collected data from American and Korean social media users to examine how the hypothesized model fits the samples from each country. The analysis of the HVIC-eWOM model within and between the two countries revealed that there are some similarities and differences in influential cultural dimensions on eWOM communications in the two countries. The results suggest that vertical aspects of individualism and collectivism are significant drivers of opinion-leadership and opinion-seeking tendencies for both countries.
Development of CAR-T Cell Persistence in Adoptive Immunotherapy of Solid Tumors

Chimeric antigen receptor (CAR) T (CAR-T) cell transfer has made great success in hematological malignancies, but only shown a limited effect on solid tumors. One of the major hurdles is the poor persistence of infused cells derived from ex vivo activation/expansion and repeated antigen encounter after re-infusion. Bcl-xL has been demonstrated to play an important role on normal T cell survival and function as well as genetically engineered cells. In the current study, we developed a retroviral CAR construct containing a second-generation carcinoembryonic antigen (CEA)-targeting CAR with the Bcl-xL gene and tested the anti-CEA CAR-T cell immunotherapy for colorectal cancer. In vitro, the anti-CEA CAR-T cells destroyed CEA-expressing tumor cells and sustained survival. In vivo, adoptive cell transfer of anti-CEA CAR-T cells significantly enhanced the ability of the CAR-T cells to accumulate in tumor tissues, suppress tumor growth and increase the overall survival rate of tumor-bearing mice in a murine model of colorectal cancer. These results demonstrate a novel CAR-T platform that has the ability to increase the persistence of CAR-T cells in solid tumors through exogenous expression of persistent genes. The data provide a potentially novel approach to augment CAR-T immunotherapy for solid tumors.
Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1

Electronic pacemakers still face major shortcomings that are largely intrinsic to their hardware-based design. Radical improvements can potentially be generated by gene or cell therapy-based biological pacemakers. Our previous work identified adenoviral gene transfer of Hcn2 and SkM1, encoding a “funny current” and skeletal fast sodium current, respectively, as a potent combination to induce short-term biological pacing in dogs with atrioventricular block. To achieve long-term biological pacemaker activity, alternative delivery platforms need to be explored and optimized. The aim of the present study was therefore to investigate the functional delivery of Hcn2/SkM1 via human cardiomyocyte progenitor cells (CPCs). Nucleofection of Hcn2 and SkM1 in CPCs was optimized and gene transfer was determined for Hcn2 and SkM1 in vitro. The modified CPCs were analyzed using patch-clamp for validation and characterization of functional transgene expression. In addition, biophysical properties of Hcn2 and SkM1 were further investigated in lentivirally transduced CPCs by patch-clamp analysis. To compare both modification methods in vivo, CPCs were nucleofected or lentivirally transduced with GFP and injected in the left ventricle of male NOD-SCID mice. After 1 week, hearts were collected and analyzed for GFP expression and cell engraftment. Subsequent functional studies were carried out by computational modeling. Both nucleofection and lentiviral transduction of CPCs resulted in functional gene transfer of Hcn2 and SkM1 channels. However, lentiviral transduction was more efficient than nucleofection-mediated gene transfer and the virally transduced cells survived better in vivo. These data support future use of lentiviral transduction over nucleofection, concerning CPC-based cardiac gene delivery. Detailed patch-clamp studies revealed Hcn2 and Skm1 current kinetics within the range of previously reported values of other cell systems. Finally, computational modeling indicated that CPC-mediated delivery of Hcn2/SkM1 can generate stable pacemaker function in human ventricular myocytes. These modeling studies further illustrated that SkM1 plays an essential role in the final stage of diastolic depolarization, thereby enhancing biological pacemaker functioning delivered by Hcn2. Altogether these studies support further development of CPC-mediated delivery of Hcn2/SkM1 and functional testing in bradycardia models.
Acute Liver Toxicity Modifies Protein Expression of Glutamate Transporters in Liver and Cerebellar Tissue

Glutamate is the main excitatory amino acid acting at the level of pre and postsynaptic neurons, as well as in glial cells. It is involved in the coordinated modulation of energy metabolism, glutamine synthesis, and ammonia detoxification. The relationship between the functional status of liver and brain has been known for many years. The most widely recognized aspect of this relation is the brain dysfunction caused by acute liver injury that manifests a wide spectrum of neurologic and psychiatric abnormalities. Inflammation, circulating neurotoxins, and impaired neurotransmission have been reported in this pathophysiology. In the present contribution, we report the effect of a hepatotoxic compound like CCl4 on the expression of key proteins involved in glutamate uptake and metabolism as glutamate transporters and glutamine synthetase in mice liver, brain, and cerebellum. Our findings highlight a differential expression pattern of glutamate transporters in cerebellum. A significant Purkinje cells loss, in parallel to an up-regulation of glutamine synthetase, and astrogliosis in the brain have also been noticed. In the intoxicated liver, glutamate transporter 1 expression is up-regulated, in contrast to glutamine synthetase which is reduced in a time-dependent manner. Taken together our results demonstrate that the exposure to an acute CCl4 insult, leads to the disruption of glutamate transporters expression in the liver-brain axis and therefore a severe alteration in glutamate-mediated neurotransmission might be present in the central nervous system.
Smartphones and Varsity Athletes: A Complicated Relationship

Varsity athletes are a group of high performers situated within a demographic notable for smartphone usage and media-multitasking. Surprisingly, little research has examined the impact of smartphones in the lives of varsity athletes. The purpose of this exploratory, qualitative study was to begin addressing this gap by investigating varsity athletes' experiences with smartphones. Varsity athletes (n = 21) from nine different sports participated in one of five focus groups, and data emerging from these discussions were subjected to an inductive thematic analysis. Results indicate that smartphones are a mainstay of varsity athletes' experiences, as the athletes regularly use their smartphones to manage roles and demands across multiple contexts (e.g., sport, school, home). Themes pertained to concurrent negative (e.g., stress, distraction, disengagement) and positive (e.g., self-regulation, social connectedness) implications of smartphone usage, making it clear that athletes' relationship with their smartphone is a complicated one. Findings contribute to the limited studies of smartphone usage among athletes, and support the notion that implications of usage exist along a continuum, rather than in distinct categories of “good” and “bad”. Results can inform practical guidelines for optimising athletes' use of smartphones in and around the sport context.
Non-linearity in the Life Cycle Assessment of Scalable and Emerging Technologies

Given a fixed product system model, with the current computational framework of Life Cycle Assessment (LCA) the potential environmental impacts associated to demanding one thousand units of a product will be one thousand times larger than what results from demanding 1 unit only – a linear relationship. However, due to economies of scale, industrial synergies, efficiency gains, and system design, activities at different scales will perform differently in terms of life cycle impact – in a non-linear way. This study addresses the issue of using the linear framework of LCA to study scalable and emerging technologies, by looking at different examples where technology scale up reflects non-linearly on the impact of a product. First, a computer simulation applied to an entire database is used to quantitatively estimate the effect of assuming activities in a product system are subject to improvements in efficiency. This provides a theoretical but indicative idea of how much uncertainty can be introduced by non-linear relationships between input values and results at the database level. Then the non-linear relations between the environmental burden per tkm of transport on one end, and the cargo mass and range autonomy on the other end is highlighted using a parametrized LCA model for heavy goods vehicles combined with learning scenarios that reflect different load factors and improvement in battery technology. Finally, a last example explores the case of activities related to the mining of the cryptocurrency Bitcoin, an emerging technology, and how the impact of scaling the Bitcoin mining production is affected non-linearly by factors such as increase in mining efficiency and geographical distribution of miners. The paper concludes by discussing the relation between non-linearity and uncertainty and by providing recommendations for accounting for non-linearity in prospective LCA studies.
Adaptability Promotes Student Engagement Under COVID-19: The Multiple Mediating Effects of Academic Emotion

In response to the COVID-19 pandemic, millions of students in China followed an emergency policy called “Suspending Classes without Stopping Learning” to continue their study online as schools across the country were closed. The present study examines how students adapted to learning online in these unprecedented circumstances. We aimed to explore the relationship between adaptability, academic emotion, and student engagement during COVID-19. 1,119 university students from 20 provinces participated in this longitudinal study (2 time points with a 2-week interval). The results showed that adaptability (the ability to respond to changes) and student engagement are significantly positively correlated with positive academic emotion and negatively correlated with negative academic emotion. Furthermore, adaptability not only directly predicts student engagement, but also affects student engagement through the chain mediation of positive academic emotion and negative academic emotion. The results contribute to the gap in knowledge regarding changes in students’ learning in response to the outbreak. This study further explains the internal mechanisms mediating the relationship between adaptability and student engagement. It may provide references for educational researchers and universities in dampening the negative effects of COVID-19 on students’ learning by improving their adaptability and developing positive academic emotions.