jimnoneill/paper-to-field-training huggingface dataset:
BMP4 reprograms glucose metabolism in hepatocellular carcinoma (HCC) cells by upregulating glycogen synthesis through the SMAD/SLC2A1 (GLUT1) signaling axis

Abstract Background Excessive hepatic glycogen accumulation benefits tumorigenesis and cancer cell survival. We previously reported that BMP4 was elevated in Hepatocellular carcinoma (HCC) and augmented HCC cell survival under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway. However, the mechanism underlying BMP4’s effect on glucose metabolism remains elusive. In this study, we investigated the effect of BMP4 on hepatic glycose metabolism through glucose transporter SLC2A1 (GLUT1) in HCC cells. Methods The expression of BMP4 and SLC2A1 were acquired by analyzing the TCGA-LIHC dataset, as well as by immunohistochemical analysis of the 40 pairs of human HCC samples and para-tumor tissues. Gene expressions were detected by qPCR, immunoflurorescence staining, and Western blotting. Overexpression and silencing of BMP4 were accomplished through adenoviruses Ad-B4 and Ad-siB4 infection. Hepatic glycogen was detected by PAS staining. SLC2A1(GLUT1) function was blocked by the inhibitor BAY-876. ChIP assay was used to determine the binding of SMADs to the promoter region of SLC2A1 in HCC cells. Lastly, the in vivo effect of BMP4-regulated SLC2A1 on HCC tumor growth was assessed in a xenograft model of HCC. Results The elevated expression of BMP4 in HCC tumor tissues was highly correlated with hepatic glycogen accumulation in clinical samples. SLC2A1 was highly expressed in HCC tumor tissue and correlated with clinical stage and prognosis. Exogenous BMP4 augmented glycogen accumulation and up regulated the expression of glycogen synthesis-related genes in Huh7 and HepG2 cells, both of which were effectively blunted by SLC2A1inhibitor BAY-876. In mechanism, BMP4 activated SMAD5 to regulate the promoter of SLC2A1to enhance its expression. The in vivo xenograft experiments revealed that BMP4 promoted glycogen accumulation and tumor growth, which were effectively diminished by BAY-876. Conclusion These results demonstrate that BMP4 can reprogram hepatic glycogen metabolism and promote tumor growth of HCC cells through SMAD/SLC2A1 axis, which may be exploited as novel therapeutic targets for HCC treatment.

Topic: Cancer, Hypoxia, and Metabolism
Subfield: Cancer Research
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Glucocorticoid receptor distribution in rat testis during postnatal development and effects of dexamethasone on immature peritubular cells in vitro.

In this study, the occurrence of the glucocorticoid receptor in the rat testis during early stages of postnatal development and its potential functional significance were investigated. Quantitative analyses of immunohistochemically labelled paraffin sections revealed that the receptor was present during all stages of postnatal development in the nuclei of interstitial cells such as Leydig cells, macrophages and fibroblasts, and endothelial cells of blood vessels. The labelling index increased initially, with maximum levels reached within the second week of postnatal development, and decreased thereafter. Within the seminiferous tubules, the glucocorticoid receptor could be detected in the nuclei of germ cells as well as Sertoli cells, reaching the highest levels in 3-week-old rats, mainly due to immature germ cell staining. In contrast, approximately 50% of the peritubular cell nuclei were stained throughout postnatal development. In vitro experiments on immature and immortalized peritubular cells demonstrated a dose-dependent and significant decrease in proliferation and fibronectin secretion after administration of dexamethasone. The data of this study suggest that glucocorticoids have a consistently repressive effect on peritubular cells throughout postnatal development. In summary, labelling of germ cells, especially in immature rats, might indicate an inhibition of spermatogenesis by corticosteroids.

Topic: Birth, Development, and Health
Subfield: Pediatrics, Perinatology and Child Health
Field: Medicine
Domain: Health Sciences
A Preliminary Evaluation of Elementary School Teachers' Willingness to Gain Certification in Science or Mathematics in an Effort Towards Achieving School-wide STEM Certification (RTP, Strand 3)

Abstract A Preliminary Evaluation of Elementary School Teachers Willingness to Gain Certification in Science or Mathematics in an Effort Towards Achieving School-wide STEM Certification (RTP, Strand 3)Teacher buy-in is critical to the success of achieving elementary school STEM certification inthe state of Georgia. The goal of the certification program is to provide educational opportunitiesin which students are prepared as 21st century learners. More than 75 percent of a school’s staffmust have a science or math endorsement or middle school science or math certification (bypassing the middle school GACE, Georgia Assessments for the Certification of Educators) or areworking on that endorsement/certification for a school to attain this status. The State of Georgiahas an initiative to increase the number of students prepared for and enrolled in STEM degreeprograms. This initiative developed in response to the critical need for science, technology,engineering, and mathematics (STEM) graduates to ensure the future success of its workforce. Inaddition, there is a necessity to develop the quantity and quality of Georgia’s P-12 science andmathematics teachers. This research focuses on evaluating early education teachers willingnessto receive STEM education training and also assisting them with introducing and implementingSTEM concepts to their students on a daily basis in their classrooms. A survey was developed toassess teachers’ current certifications, comfort level with math and science education, andwillingness to receive additional training, if necessary, in one Georgia elementary school.Preliminary survey results indicate that the majority of teachers were not adequately trained andhad a low level of interest and willingness to receive additional training. This research willpresent the final results of a school-wide survey as well as present an action plan for furtherteacher engagement and buy-in towards the achievement of STEM certification for the school.

Topic: Agricultural and Financial Auditing
Subfield: General Agricultural and Biological Sciences
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Fucosyltransferases: Differential plasma and tissue alterations in hepatocellular carcinoma and cirrhosis

To determine whether abnormal metabolism of l-fucose in hepatocellular carcinoma is accompanied by alterations in the activities of fucosyltransferases, the latter were determined in plasma and liver tissue of patients with this disease and in cirrhotic and normal subjects. Activities of α-2/α-3 and α-6-l -fucosyltransferases were all significantly greater in plasma from patients with hepatocellular carcinoma than in plasma from cirrhotic patients or normal subjects (p &lt; 0.025). The activity of each enzyme was dependent, to a similar extent, on Mn 2+ , Mg 2+ and triton X-10, irrespective of the source, and all displayed pH optimums in the range of 7.5 to 8.0. In contrast, activities of α-2/α-3 fucosyltransferases were significantly lower (p &lt; 0.025) in homogenates prepared from tumorous liver tissue than in that prepared from nontumorous tissue from hepatocellular carcinoma and cirrhotic patients, whereas for the α-6 enzyme the situation was reversed (typically, tumor tissue levels were 5 pmol/hr/mg; in nontumor tissue they were 2 pmol/hr/mg). Activities of galactosyl and mannosyltransferase in tumor tissue were greater in all cases than in nontumor cirrhotic tissue. Plasma fucosyltransferases are specifically elevated in hepatocellular carcinoma but different mechanisms appear to underlie the changes seen for α-2/α-3 and α-6-l-fucosyltransferases. (Hepatology 1991;13:683-688.)

Topic: Glycosylation and Glycoproteins Research
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Medical devices; clinical chemistry and clinical toxicology devices; classification of newborn screening test systems for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. Final rule.

The Food and Drug Administration (FDA) is classifying newborn screening test systems for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Newborn Screening Test Systems for Amino Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, the Food and Drug Administration Modernization Act of 1997, and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Topic: Pharmaceutical studies and practices
Subfield: Pediatrics, Perinatology and Child Health
Field: Medicine
Domain: Health Sciences
Napping During Night Shift: Practices, Preferences, and Perceptions of Critical Care and Emergency Department Nurses

Background Nurses working night shifts are at risk for sleep deprivation, which threatens patient and nurse safety. Little nursing research has addressed napping, an effective strategy to improve performance, reduce fatigue, and increase vigilance. Objective To explore nurses’ perceptions, experiences, barriers, and safety issues related to napping/not napping during night shift. Methods A convenience sample of critical care nurses working night shift were interviewed to explore demographics, work schedule and environment, and napping/ not napping experiences, perceptions, and barriers. Transcripts were constantly compared, and categories and themes were identified. Results Participants were 13 critical care nurses with an average of 17 years’ experience. Ten nurses napped regularly; 2 avoided napping because of sleep inertia. The need for and benefits of napping or not during night shift break were linked to patient and nurse safety. Ability to nap was affected by the demands of patient care and safety, staffing needs, and organizational and environmental factors. Conclusions Nurses identified personal health, safety, and patient care issues supporting the need for a restorative nap during night shift. Barriers to napping exist within the organization/work environment.

Topic: Sleep and Work-Related Fatigue
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Phytochemical study of <i>Glycyrrhiza pallidiflora</i> Maxim.

This article presents the results of the primary phytochemical study of Glycyrrhiza pallidiflora Maxim. introduced in the southeast of Western Siberia. The qualitative and quantitative composition of several primary and secondary metabolites in underground and aboveground organs of the plant were studied in different years of introduction and vegetation period. The presence of triterpene saponins, coumarins, chromones, chalcones, aurones, 5-oxy-flavones, 5-oxy-flavonols, flavan-3-ols, and proanthocyanidins was determined. The total content of phenolic compounds in the grass reached 2.83±0.22% and in the roots up to 0.77±0.27%. Eighteen proteinogenic amino acids were identified, including 8 essential and 10 nonessential amino acids. The seeds were found to accumulate 4.27±0.25% of fatty oils with a predominance of triglycerides of polyunsaturated acids.

Topic: Pharmacological Effects of Natural Compounds
Subfield: Pharmacology
Field: Pharmacology, Toxicology and Pharmaceutics
Domain: Life Sciences
Protein sequence design on given backbones with deep learning

Abstract Deep learning methods for protein sequence design focus on modeling and sampling the many- dimensional distribution of amino acid sequences conditioned on the backbone structure. To produce physically foldable sequences, inter-residue couplings need to be considered properly. These couplings are treated explicitly in iterative methods or autoregressive methods. Non-autoregressive models treating these couplings implicitly are computationally more efficient, but still await tests by wet experiment. Currently, sequence design methods are evaluated mainly using native sequence recovery rate and native sequence perplexity. These metrics can be complemented by sequence-structure compatibility metrics obtained from energy calculation or structure prediction. However, existing computational metrics have important limitations that may render the generalization of computational test results to performance in real applications unwarranted. Validation of design methods by wet experiments should be encouraged.

Topic: Protein Structure and Dynamics
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Reference Intervals for and the Effects of Sample Handling and Sex on Rotational Thromboelastometry in Healthy Adult Pigs

Accurate assessment of coagulation in porcine studies is essential. We sought to establish normal values for porcine rotational thromboelastometry (ROTEM) according to the American Society for Veterinary Clinical Pathology guidelines and to assess the effects of various preanalytical parameters on those measurements. Healthy Yorkshire-cross pigs ( n = 81; 46 males and 35 females) were anesthetized. By using a 18-gauge needle attached to a vacuum phlebotomy tube, blood was acquired from the cranial vena cava. Tubes were filled in the following order: evacuation clot tube, EDTA tube, heparin tube, and 2 citrate tubes. The citrate tubes were randomly assigned to 30 min with or without constant agitation on a rocker. The following parameters were reported according to the manufacturer's recommendations: clotting time, clot formation time, α, (tangent to the clot formation curve when the clot firmness is 20 mm), clot firmness after 10 and 20 min, maximal clot firmness, maximum lysis, and lysis indexes at 30 and 45 min. Reference intervals were reported as mean ± 2 SD (parametric distribution) or 2.5th and 97.5th percentile of the population's results (nonparametric distribution). The effects of sex, sampling order, and agitation on ROTEM results were analyzed through linear regression. Neither sex nor sample agitation influenced any of the ROTEM parameters. Combined reference intervals were established for each ROTEM parameter by pooling data from the nonagitated tubes for both male and female pigs. This study is the first to establish ROTEM reference intervals from a large number of male and female adult Yorkshire-cross pigs and to provide a detailed description of preanalytical sample processing.

Topic: Trauma, Hemostasis, Coagulopathy, Resuscitation
Subfield: Critical Care and Intensive Care Medicine
Field: Medicine
Domain: Health Sciences
Aging effects on the ability to use temporal context in speech perception

Elderly and young adults listened to a continuum of stimuli varying in closure duration from “rabid” to “rapid” presented at fast and normal speaking rates, with a carrier phrase and in isolation. Rates for the phrase and word were either consistent or conflicting, to determine the relative influence of extrinsic versus intrinsic temporal cues. In addition, the effect of intensity level was examined for all the above conditions. Hearing sensitivity was within normal limits through the low-pass cutoff frequency (3.15 kHz) for the filtered speech. In contrast to previous findings with isolated words [P. J. Price and H. J. Simon, J. Acoust. Soc. Am. 76, 406–509 (1984)], no significant overall age effects were seen for either the word alone conditions at the higher intensity or for any of the phrase + word conditions. These results suggest that, when hearing sensitivity is controlled, age per se may not explain the increased difficulty that many elderly have in processing fast speech. Follow-up research is planned to determine why these data conflict with previous findings.

Topic: Hearing Loss and Rehabilitation
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Modeling and measurement internal threat process based on advanced stochastic model

Previous research on internal threats was mostly focused on modeling threat behaviors. These studies have paid little attention to risk measurement. This paper analyzed the internal threat scenarios, introduced the operation related protection model into the firewall-password model, constructed a series of sub models. By analyzing the illegal data out process, the analysis model of target network can be rapidly generated based on four protection sub-models. Then the risk value of an assessment point can be computed dynamically according to the Petri net computing characteristics and the effectiveness of overall network protection can be measured. This method improves the granularity of the model and simplifies the complexity of modeling complex networks and can realize dynamic and real-time risk measurement.

Topic: Network Security and Intrusion Detection
Subfield: Computer Networks and Communications
Field: Computer Science
Domain: Physical Sciences
Future hydrology and climate in the River Nile basin

A critical discussion of recent studies that analysed the effects of climate change on the water resources of the River Nile Basin (RNB) is presented. First, current water-related issues on the RNB showing the particular vulnerability to environmental changes of this large territory are described. Second, observed trends in hydrological data (such as temperature, precipitation, river discharge) as described in the recent literature are presented. Third, recent modelling exercises to quantify the effects of climate changes on the RNB are critically analysed. The many sources of uncertainty affecting the entire modelling chain, including climate modelling, spatial and temporal downscaling, hydrological modelling and impact assessment are also discussed. In particular, two contrasting issues are discussed: the need to better recognize and characterize the uncertainty of climate change impacts on the hydrology of the RNB, and the necessity to effectively support decision-makers and propose suitable adaptation strategies and measures. The principles of a code of good practice in climate change impact studies based on the explicit handling of various sources of uncertainty are outlined.

Topic: Transboundary Water Resource Management
Subfield: Sociology and Political Science
Field: Social Sciences
Domain: Social Sciences
A comparison of parallel- and series elastic elements in an actuator for mimicking human ankle joint in walking and running

Elastic elements in prosthetic devices can help to reduce peak power (PP) and energy requirements (ER) for the actuators. Calculations showed that it is impossible with current commercial motor technology to mimic human ankle behavior in detail for higher walking and running speeds with single motor solutions using a Serial Elastic Actuator (SEA). Concerning this result we checked the requirements of a parallel elastic actuator (PEA) and a combination of serial and parallel (SE+PEA) springs. We found that a PEA can reduce PP additionally in comparison to the SEA by pre-loading the spring in the flight phase. This reduces also peak torque. But this loading needs additional energy so that the ER increase in comparison to the SEA. The SE+PEA concept can further decrease PP. With that, the ER are less than the PEA but higher than for the SEA. The results show less benefit for the PEA and the SE+PEA when a constant stiffness and a fixed parallel spring slack length is used for both gaits and all speeds. All concepts show that mimicking human ankle joint behavior in running and walking at higher speeds is still challenging for single motor devices.

Topic: Prosthetics and Rehabilitation Robotics
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Primary ciliary dyskinesia: improving the diagnostic approach

The diagnosis of primary ciliary dyskinesia (PCD) has relied on analysis of ciliary motility and ultrastructure; however, these tests are not readily available and have not been standardized. Consequently, the diagnosis of PCD may be delayed or missed or made incorrectly. This review outlines the potential utility of new diagnostic tests, including measurement of nasal nitric oxide (NO) production and systematic analysis for mutations in gene encoding ciliary proteins.

Topic: Cystic Fibrosis Research Advances
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Updates in microsurgical technique for cleft palate reconstruction

Background: The soft palate is a crucial structure that plays a vital role in maintaining the airway open, facilitating swallowing, and enabling speech. Excisional surgery that disrupts the functional architecture of the soft palate leads to considerable morbidity, and neither prosthetic nor flap reconstructions can adequately restore the intrinsic velar musculature. The primary objectives in treating oral malignancies that impact the soft palate are to attain oncological control and minimize the occurrence of complications and undesired consequences. In the present age of microsurgical practice, teams are striving to not only accomplish oncological excision and successful flap procedures but also to enhance functional results. In this case, a suprafascial ALT flap was surgically created to provide extra volume and optimize the functional benefit of the remaining velar muscles. The treatment method depends on the dimensions of the defect and the anatomical components removed. For full-thickness injuries, direct repair is recommended, while for full-thickness, "near-total to total," greater than 70%, a nonanatomic reconstruction is carried out, and a fascial sling is included to constrict the velopharynx. Tips for addressing velopharyngeal constriction include using a two-layer closure technique, using a fascial sling, positioning the skin vessel/perforator, incorporating the vastus lateralis muscle, maintaining a minimum distance between the point of entrance into the muscle and the point where the perforator branches off, and verifying the vitality of the muscle prior to completing the closure. In conclusion, employing an anterolateral thigh (ALT) free flap technique for palate reconstruction achieves favorable functional results with minimal complications at the donor site. Keywords: Microsurgery, cleft palate, free flap

Topic: Cleft Lip and Palate Research
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences