jimnoneill/paper-to-field-training huggingface dataset:
From Type I to Type II: Design, Synthesis, and Characterization of Potent Pyrazin‐2‐ones as DFG‐Out Inhibitors of PDGFRβ

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Abstract Reversible protein kinase inhibitors that bind in the ATP cleft can be classified as type I or type II binders. Of these, type I inhibitors address the active form, whereas type II inhibitors typically lock the kinase in an inactive form. At the molecular level, the conformation of the flexible activation loop holding the key DFG motif controls access to the ATP site, thereby determining an active or inactive kinase state. Accordingly, type I and type II kinase inhibitors bind to so‐called DFG‐in or DFG‐out conformations, respectively. Based on our former study on highly selective platelet‐derived growth factor receptor β (PDGFRβ) pyrazin‐2‐one type I inhibitors, we expanded this scaffold toward the deep pocket, yielding the highly potent and effective type II inhibitor 5 (4‐[(4‐methylpiperazin‐1‐yl)methyl]‐ N ‐[3‐[[6‐oxo‐5‐(3,4,5‐trimethoxyphenyl)‐1 H ‐pyrazin‐3‐yl]methyl]phenyl]benzamide). In vitro characterization, including selectivity panel data from activity‐based assays (300 kinases) and affinity‐based assays (97 kinases) of these PDGFRβ type I ( 1 ; 5‐(4‐hydroxy‐3‐methoxy‐phenyl)‐3‐(3,4,5‐trimethoxyphenyl)‐1 H ‐pyrazin‐2‐one) and II ( 5 ) inhibitors showing the same pyrazin‐2‐one chemotype are compared. Implications are discussed regarding the data for selectivity and efficacy of type I and type II ligands.
A night in the life of a migrant street artist: In conversation with visual artist Shp

Field: Arts and Humanities (Social Sciences)

The following text is a transcription and translation from a conversation with Eduardo Santos, a Brazilian tagger and street artist who currently lives in Lisbon, Portugal. Santos, more widely known as Shp (‘sheep’), member of the group Pregos (literally translated as ‘nails’), responded to questions about identity, life philosophy and art through a series of WhatsApp audios. In addition, Shp and Xiên, another Brazilian migrant, provide a voice-over for a ten-minute video that shows a ‘night in the life’ of a pixador, the name given in Brazilian Portuguese to a street artist who practises the Brazilian variant that mixes elements of tagging and graffiti. Topics broached include: a comparison between pixo and Brazilian funk, marginalized arts, the street, the origins of pixo in Lisbon, respect and the presence of Brazil in the tuga (Portugal). English subtitles were done by Mariana Gil, a Brazilian photographer and migrant living in Aarhus, Denmark (video link: https://www.instagram.com/tv/CQYue_MnUuk/?utm_medium=copy_link ).
Transformer Inrush Measurements in a Distribution Grid Laboratory

Field: Engineering (Physical Sciences)

This data set contains measurement data of distribution transformer inrush transients obtained in the Distribution Grid Laboratory at the IAEW at RWTH Aachen University. Within the framework of the investigations, a medium voltage feeder with one or multiple medium/low voltage transformers is energised. The setup is either supplied by the public medium voltage grid or by a grid-forming converter. In the latter case, grid voltage distortions can be observed during the inrush transient due to output current limitation of the converter. The inrush measurements were carried out within the framework of the project DiSCo (Distribution System Inrush From Grid-Forming Converters). The authors gratefully acknowledge funding by E.ON SE as well as the technical support in development, execution and analysis of the experimental investigations by Westnetz GmbH. In addition, we would like to thank the colleagues of the Institute for Power Generation and Storage Systems (PGS) for their support and the informative discussions.
Neonatal Eye Defects and Stem Cell Therapeutics

Field: Medicine (Health Sciences)

Present review aims to describe various neonatal eye defects and its stem cell therapeutics. This article attempts to highlight common causes of visual impairment in infants and present the recent approaches used for restoration of normal vision in patients. The article highlights the need for setting microenvironment or stem cell micro niche for regeneration of opticneural complexes. Till date no proven drug based treatment existed for inherited eye defects. By adopting different therapeutic measures causal effects can be improved. The article advocates cell based therapeutics for wound healing of optical tissues for functional restoration using appropriate and suitable cell transplantations in animal models. In addition, possible solutions have been suggested to reduce the pain in newborns and infants from serious life-threatening visual complications or infection induced visual pathogenesis. This article emphasizes use of stem cell derived lens cells for human lens development and regeneration of corneal and retinal cells for increasing future therapeutic applications. As an alternative remedy exploring and designing new biomaterials to make matrix based nano-structure constructs for corneal repair and regeneration has been suggested. Bioengineered corneal devices are addressed with safe use of tissue-engineered hydrogels to allow regeneration of radiosensitivity in neural-visual cell complex. Present review presents new advancements in the field of biocompatible substrates, bio-matrix, transplantation methods and micro-niche maintaining factors for restoration, repairing and healing of visual-neuroepithelial complexes successfully.
Epigenetic Gene Regulation in the Bacterial World

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

SUMMARY Like many eukaryotes, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Unlike eukaryotes, however, bacteria use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation plays roles in the virulence of diverse pathogens of humans and livestock animals, including pathogenic Escherichia coli , Salmonella, Vibrio, Yersinia, Haemophilus , and Brucella . In Alphaproteobacteria , methylation of adenine at GANTC sites by the CcrM methylase regulates the cell cycle and couples gene transcription to DNA replication. In Gammaproteobacteria , adenine methylation at GATC sites by the Dam methylase provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage genomes, transposase activity, and regulation of gene expression. Transcriptional repression by Dam methylation appears to be more common than transcriptional activation. Certain promoters are active only during the hemimethylation interval that follows DNA replication; repression is restored when the newly synthesized DNA strand is methylated. In the E. coli genome, however, methylation of specific GATC sites can be blocked by cognate DNA binding proteins. Blockage of GATC methylation beyond cell division permits transmission of DNA methylation patterns to daughter cells and can give rise to distinct epigenetic states, each propagated by a positive feedback loop. Switching between alternative DNA methylation patterns can split clonal bacterial populations into epigenetic lineages in a manner reminiscent of eukaryotic cell differentiation. Inheritance of self-propagating DNA methylation patterns governs phase variation in the E. coli pap operon, the agn43 gene, and other loci encoding virulence-related cell surface functions.
Forms of Violence Faced by Children during Their Discipline in Islamic Thought and International Law

Field: Social Sciences (Social Sciences)

This study aims to achieve the following: knowing the forms of violence faced by children during their discipline, knowing the attitude of pioneers of Islamic thought, international laws and universal declarations of children rights towards violence against children during their discipline and providing the right alternative means to discipline children. The study reached the following results: the use of a soft and kind method in disciplining children instead of using violence against them has good effect on the children. Disciplining children with violence has a negative impact on the their mental and physical health and international laws, conventions and declarations have emphasised the criminalisation of the use of violence and cruelty against children in all circumstances.
Ultralow-Power Operation in Subthreshold Regimes Applying Clockless Logic Newlogiccircuitspromisetoprovideexceptionalthroughputandenergysavingswhen thesupplyvoltageislessthanthethresholdvalueneededtosustainnormaloperation.

Field: Engineering (Physical Sciences)

Energy performance requirements are causing designers of next-generation systems to explore approaches to lowest possible power consumption. Subthreshold operation is being examined to stretch low-power circuit designs beyond the normal modes of operation, with the potential for large energy savings. Some of the challenges to be overcome, like 10-100� performance penalties, are being addressed by re- search into parallelism. However, the uncertainty in timing generated by operating in subthreshold represents a major challenge to overcome. In this paper, first, we will introduce some background information on digital logic subthreshold operation, then provide some background on clockless logic design approaches giving a brief overview of some of the characteristics of the different design styles and focusing on NULL convention logic. Next, we will examine the applica- tion of that clockless logic approach to a military system, reviewing the background of the experiment, factors consid- ered in the comparison, and then summarizing the results of the comparisons. Finally, an overview of additional research and development that will be needed to make the technique available to subthreshold designers is presented.
High expression of TAZ/YAP promotes the progression of malignant melanoma and affects the postoperative survival of patients.

Field: Medicine (Health Sciences)

Background: YAP/TAZ have been reported to be highly expressed in malignant tumors. This research was aimed to study the expression of TAZ/YAP protein in malignant melanoma and to investigate its relationship to the clinicopathology and prognosis of patients with malignant melanoma. Methods: A total of 156 pairs of malignant melanoma tumor tissues and melanocytic nevi tissues were collected. The expression of TAZ and YAP proteins were detected by immunohistochemistry and western blotting. Relationship between TAZ/YAP and clinical data of malignant melanoma were analyzed. Results: The number of positive cells of TAZ and YAP in malignant melanoma tumor tissues was significantly higher than that in melanocytic nevi tissues, and the expression of both proteins was positively correlated with malignant melanoma (r = 0.687, P <0.01); TAZ and YAP protein expression in malignant melanoma tissue was significantly correlated with tumor thickness, invasive depth grade, lymph node metastasis and TNM stages (P <0.05), and increased with TNM staging. The expression of TAZ and YAP in patients with lymph node metastasis was significantly higher than that in non-metastatic patients (P <0.05). High expression of TAZ/YAP significantly reduced the postoperative survival rate in patients with malignant melanoma. Conclusion: TAZ/YAP is highly expressed in malignant melanoma tumor tissues. The high expression of TAZ/YAP promotes the progression of malignant melanoma and affects the postoperative survival of patients.
Teratogenetic properties of thalidomide.

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Background: We retrospectively analyzed the efficacy and safety of lenvatinib in 12 patients with advanced radioiodine-refractory thyroid cancer in the setting of daily clinical practice. Patients and Methods: The starting daily dose of lenvatinib was 24 mg, tapered in the case of adverse events. Disease status was periodically evaluated by a single radiologist and safety assessment was regularly performed. Results: After a median follow-up of 13.3 months, 6- and 12-month progression-free survival rates were 63.6% and 54.6%, respectively. Overall survival at 6 and 12 months was 83.3% and 75.0%. Partial response was observed in five patients, while two showed stable disease as their best response. Conversely, progressive disease at first radiological assessment was detected in four patients. All patients experienced at least one adverse event, including systemic and gastrointestinal toxicity, high blood pressure and hand–foot syndrome. In order to manage toxicity, transient drug interruption and dose reduction were required in 10 and 9 cases, respectively. Conclusion: Our data confirm lenvatinib efficacy in patients with advanced thyroid cancer, despite an important toxic profile.
IoT-Enabled Non-Contact-Based Infrared Thermometer for Temperature Recording of a Person

Field: Engineering (Physical Sciences)

Laboratories are essential facilities provided in professional institutes for scientific and technological work. The lab must ensure their accuracy to regulatory requirements and maintain their data records so that the laboratory environment can be monitored properly. The laboratory environment temperature (LET) is monitored to ensure proper regulation and maintenance of indoor conditions and also to correlate the collected samples with these conditions. The LET data collection must be stored to influence the quality of the results and to ensure the stability of the laboratory environment. Hence, an IoT solution is presented to supervise real-time temperature and is known as iRT. This method helps to monitor ambient object supervision in real time. It is composed of a hardware prototype to collect the temperature data and to use web application to provide the history of temperature evolution. The result gained from the study is promising, and it provides a significant contribution to IoT-based temperature monitoring systems.
The effect of nerve growth factor on the development of sodium channels in PC12 cells

Field: Neuroscience (Life Sciences)

We have studied the development of the action potential Na + channels in PC12 cells, an established line that has been useful as a model for neuronal differentiation. In continuous culture PC12 cells, although electrically inexcitable, nevertheless have a low level of Na + channels as judged by the increase in 22 Na + uptake in the presence of veratridine and scorpion toxin. These two neurotoxins have been shown to promote activation of Na + channels in a variety of electrically excitable cells. Following treatment with nerve growth factor (NGF), conditions which induce differentiation to an electrically excitably neuronal-cell type, the neurotoxin-activated 22 Na + uptake increases approximately 12-fold, on a per cell basis, reaching a maximum in 12–16 days. The dose–response curves for veratridine and scorpion toxin are unchanged by NGF treatment (K 0.5 for veratridine, 18–14 μM; K 0.5 for scorpion toxin, 120–96 nM). Na + channels in both undifferentiated and differentiated cells are tetrodotoxin sensitive and NGF treatment has no effect on the inhibition constant (K i , 10–12 nM). Na + channel sites were measured directly by the specific binding of [ 3 H]saxitoxin. In NGF-treated cells, the saxitoxin receptor density reaches 154 fmol/mg protein (K d , 1.3 nM), a level comparable to other excitable cells. Levels in control cells were too low to measure accurately. These findings show that NGF treatment of PC12 cells leads to a substantial increase in the expression of neurotoxin-sensitive Na + channels. Furthermore, these channels are pharmacologically similar, if not identical, to those which exist in undifferentiated cells and therefore do not appear to result from the conversion of preexisting channels.
One More Mission for a Multi-mission Platform: An Argument for Support Relationships for Theater Missile Defense

Field: Engineering (Physical Sciences)

Abstract : Establishing effective national missile defense is a top priority for the United States military. Improved missile defense assets, including the development of Aegis ballistic missile defense (BMD), provide a strategic deterrent and a limited ability to defeat ballistic missile attacks. Operational commanders must leverage the assets developed for national missile defense to counter the more prevalent, likely and challenging threat of theater ballistic missiles. To do so requires the application of sound operational art. Specifically, clearly defined command and control relationships that ensure effective and sustained joint theater missile defense (TMD) are needed. The thesis of this paper is that a support relationship is the optimal C2 relationship for Aegis ships in TMD because it best provides the necessary logistics and protection for the Aegis BMD assets without sacrificing their efficacy in traditional maritime missions. This paper provides background information about the operational capabilities and limitations of Aegis BMD and discusses important distinctions between national and theater missile defense. Then it explains why the support relationship is best suited for Aegis BMD in the TMD mission and offers recommendations to ensure effective TMD C2 relationships are established.
Concomitant cardiac and pulmonary operations for lung cancer.

Field: Medicine (Health Sciences)

From 1973 through 1990, 21 patients (17 men and 4 women) underwent concomitant cardiac operation and pulmonary resection for lung cancer. The mean age was 65.3 years (range, 50 to 80 years). Eighteen patients underwent coronary artery bypass; 1 underwent coronary bypass and mitral valve replacement; 1, aortic valve replacement; and 1, left ventricular aneurysmectomy. Pulmonary procedures included 16 lobectomies, 3 segmentectomies, and 2 wedge resections. Nine resections were performed during cardiopulmonary bypass, and 12 were performed either before or after bypass. On final pathologic diagnosis, 11 patients had adenocarcinoma, 7 had squamous cell carcinoma, and 3 had undifferentiated lesions. Twelve patients were in cancer stage 1 and 9 were in stage II. Placement of an intraaortic balloon pump was required in 3 patients. No patient sustained excessive blood loss requiring reoperation. Only 2 incidents (9.5%) of disseminated infection were reported. The overall 1-year survival rate was 90.5% and the 5-year survival rate was 52.4%. We found concomitant cardiac operation and pulmonary resection for lung cancer to be a safe and effective alternative to staged treatment in patients not requiring a pneumonectomy. Combined cardiac and pulmonary surgery spares the patient the risk and cost of a 2nd major surgical procedure without compromising long-term survival.
Creative Contributions of the Methods of Inventive Principles of TRIZ and BioTRIZ to Problem Solving

Field: Decision Sciences (Social Sciences)

This study compares the potential of the methods of inventive principles (IPR) of TRIZ (MIPT) and BioTRIZ (MIPB) in relation to stimulating creativity in problem solving. The two methods were applied to different issues by groups of undergraduate students. The solutions were evaluated in terms of creativity, which was defined by the criteria of originality and utility. Quantitative analysis provided evidence that the two methods are equal in terms of creative contributions. However, further analyses indicate that the IPs derived from biological systems tend to provide a greater creative contribution compared to those based on technical systems. In addition, it was found that repeated inventive principles (IPR), that is, those indicated more than once by the applied methods, tend to introduce a greater potential for stimulating creativity compared to inventive principles (IPs) indicated only once.
Synthetic aperture ladar based on a MOPAW laser

Field: Physics and Astronomy (Physical Sciences)

Long range land surveillance is a critical need in numerous military and civilian security applications, such as threat detection, terrain mapping and disaster prevention. A key technology for land surveillance, synthetic aperture radar (SAR) continues to provide high resolution radar images in all weather conditions from remote distances. State of the art SAR systems based on dual-use satellites are capable of providing ground resolutions of one meter; while their airborne counterparts obtain resolutions of 10 cm. Certain land surveillance applications such as subsidence monitoring, landslide hazard prediction and tactical target tracking could benefit from improved resolution. The ultimate limitation to the achievable resolution of any imaging system is its wavelength. State-of-the-art SAR systems are approaching this limit. The natural extension to improve resolution is to thus decrease the wavelength, i.e. design a synthetic aperture system in a different wavelength regime. One such system offering the potential for vastly improved resolution is Synthetic Aperture Ladar (SAL). This system operates at infrared wavelengths, ten thousand times smaller radar wavelengths. This paper presents a SAL platform based on the INO Master Oscillator with Programmable Amplitude Waveform (MOPAW) laser that has a wavelength sweep of Δλ=1.22 nm, a pulse repetition rate up to 1 kHz and up to 200 μJ per pulse. The results for SAL 2D imagery at a range of 10 m are presented, indicating a reflectance sensibility of 8 %, ground-range and azimuth resolution of 1.7 mm and 0.84 mm respectively.
Isopropyl available for citrus: Registration of the isopropyl ester specifically for use as plant growth regulator on citrus permits this form of 2,4-D

Field: Agricultural and Biological Sciences (Life Sciences)

The value of 2,4-D and related substances for preventing mature citrus fruit drop, for increasing fruit size, and for amending oil spray used for pest control to prevent leaf drop or fruit drop—or both—has been demonstrated.
Evaluation of genotoxic and cytologic effects of environmental stressin wheat species with different ploidy levels

Field: Agricultural and Biological Sciences (Life Sciences)

Drought and salinity induce biochemical, physiological, morphological, and genetic responses in plants. To understand the damage to different wheat species caused by these stresses, we investigated root-shoot growth, cell division, chromosomal aberrations, and nucleolus organizer regions (AgNORs) in root tip cells. Inhibition of root and shoot growth were observed in diploid, tetraploid, and hexaploid wheat genotypes after salt and drought stresses. Both stresses had adverse effects on dividing cells in root tips of all wheat species and caused a decrease in mitotic index values. Salt and drought lead to the induction of chromosome aberrations and repression of interphase AgNOR parameters. Both treatments produced different mitotic abnormalities including chromosomal stickiness, c-mitosis, and micronuclei formation, which indicated their action on the mitotic spindle. Reduction in AgNOR parameters showed that salt and drought may decrease the level of ribosomal biogenesis and reduce the length of the cell cycle. Because of the toxicity of Na ions, salinity inhibited all parameters at a higher degree than drought in all Triticum species. Cytotoxic effects of salinity and drought were mainly observed in meristematic cells in all wheat species. This comprehensive analysis may provide valuable information for understanding the effects of salt and drought stresses on cytogenetics of wheat species.
Six New Genera in the Chaetognath Family Sagittidae

Field: Agricultural and Biological Sciences (Life Sciences)

The following six new genera of Sagittidae, with type species listed in parentheses, are proposed: Adhesisagitta (Sagitta hispida Conant, 1985), Demisagitta (Sagitta demipenna Tokioka and Pathansali, 1963), Decipisagitta (Sagitta decipiens Fowler, 1905), Tenuisagitta (Sagitta tenuis Conant, 1986), Abacisagitta (Sagitta pulchra Doncaster, 1903), Oculosagitta (Sagitta megalophthalma Dallot and Ducret, 1969).