jimnoneill/paper-to-field-training huggingface dataset:
Metformin Is a Pyridoxal-5′-phosphate (PLP)-Competitive Inhibitor of SHMT2

The anticancer actions of the biguanide metformin involve the functioning of the serine/glycine one-carbon metabolic network. We report that metformin directly and specifically targets the enzymatic activity of mitochondrial serine hydroxymethyltransferase (SHMT2). In vitro competitive binding assays with human recombinant SHMT1 and SHMT2 isoforms revealed that metformin preferentially inhibits SHMT2 activity by a non-catalytic mechanism. Computational docking coupled with molecular dynamics simulation predicted that metformin could occupy the cofactor pyridoxal-5′-phosphate (PLP) cavity and destabilize the formation of catalytically active SHMT2 oligomers. Differential scanning fluorimetry-based biophysical screening confirmed that metformin diminishes the capacity of PLP to promote the conversion of SHMT2 from an inactive, open state to a highly ordered, catalytically competent closed state. CRISPR/Cas9-based disruption of SHMT2, but not of SHMT1, prevented metformin from inhibiting total SHMT activity in cancer cell lines. Isotope tracing studies in SHMT1 knock-out cells confirmed that metformin decreased the SHMT2-channeled serine-to-formate flux and restricted the formate utilization in thymidylate synthesis upon overexpression of the metformin-unresponsive yeast equivalent of mitochondrial complex I (mCI). While maintaining its capacity to inhibit mitochondrial oxidative phosphorylation, metformin lost its cytotoxic and antiproliferative activity in SHMT2-null cancer cells unable to produce energy-rich NADH or FADH2 molecules from tricarboxylic acid cycle (TCA) metabolites. As currently available SHMT2 inhibitors have not yet reached the clinic, our current data establishing the structural and mechanistic bases of metformin as a small-molecule, PLP-competitive inhibitor of the SHMT2 activating oligomerization should benefit future discovery of biguanide skeleton-based novel SHMT2 inhibitors in cancer prevention and treatment.

Topic: Metabolism, Diabetes, and Cancer
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Deriving Basic Living Service Items and Establishing Spatial Data in Rural Areas

This study aims to derive basic living service facility items in rural areas and construct related spatial data. To do this, a literature review on the laws and systems related to the residential environment and services in rural areas, rural spatial planning, and the ‘Rural Convention’ strategic plan reports for the Jeolla and Gyeongsang Region in 2021 was conducted. Primary data collection and review on the list of basic living service items in rural areas derived from the analysis were conducted. After data collection, 12 sectors and 44 types of rural basic living service items were derived; the data selection was carried out based on the clarity of the subject of data management, whether it was established nationwide, whether it was disclosed and provided, whether it was periodically updated, and whether it was an underlying law. Afterwards, data on the derived rural basic living service items were constructed. Afterwards, spatial data on the derived rural basic living service items were constructed. Because open data provided through various institutions were employed, data structure unification such as data attribute values and code names was needed, and abnormal data such as address errors and omissions were refined. After that, the data provided in text form was converted into spatial data through geocoding, and through comparative review of the distribution status of the converted data and the provided address, spatial data related to rural basic living services were finally constructed for about 540,000 cases. Finally, implications for data construction for diagnosing rural living areas were derived through the data collection and construction process. The derived implications include data unification, data update system establishment, the establishment of attribute values necessary for rural living area diagnosis and spatial planning, data establishment plan for facilities that provide various services, rural living area analysis method, and diagnostic index development. This study is meaningful in that it laid the foundation for data-based rural area diagnosis and rural planning, by selecting the basic rural living service items, and constructing spatial data on the selected items.

Topic: Korean Urban and Social Studies
Subfield: Management, Monitoring, Policy and Law
Field: Environmental Science
Domain: Physical Sciences
Divergent Patterns of Confrontation With Death Using the Anticipated Farewell to Existence Questionnaire (AFEQT): Cross-Sectional Comparative Study of Four Samples With Increasing Proximity to Death.

Abstract Background: Based on the concept of “ Daseinsverabschiedung ”, an anthropological theory of “Anticipated Farewell to Existence” (AFE) was suggested on the basis of six grounding dimensions (“derived in AFE”): selfhood (“expiration of the time of existence”), interpersonality (“altruistic preoccupation”), temporality (“struggle for acceptance”), corporeality (“wounded physical integrity”), worldliness (“reconciliation with own existence”), and transcendence (“self-transcendence”). The purpose of the study is to investigate the extent to which the relevance of these anthropological dimensions differs between people in different stages of life, especially those facing their own death. Methods: The sample (N=485) consists of dying individuals in palliative wards and hospices (n=121); old people living in nursing homes not suffering from a mortal disease (n=62); young adults (n=152), and middle-aged adults (n=150). The relevance of anticipated farewell to existence was measured by means of the “Anticipated Farewell to Existence Questionnaire” (AFEQT). Further assessment tools: Big Five Inventory (BFI-10), Life Attitude Profile (LAP-R), Eastern Cooperative Oncology Group (ECOG), and Basic Documentation for Psycho-Oncology (PO-Bado). The internal consistency of the AFEQT was assessed using Cronbach’s alpha and convergent validity by means of dimensions of LAP-R. Differences in the relevance of the AFEQT dimensions among stages of life were estimated by means of multiple regression models. Results: According to Cronbach’s alpha, the internal consistency of the AFEQT subscales was sufficient for the whole sample. Convergent validity with dimensions of LAP-R was found for young and middle-aged participants. Dying people scored significantly higher for most of the dimensions than young and middle-aged as well as elderly people. Personality traits of “oenness” and “agreeableness” are positively associated with the extent of assessed dimensions of AFEQT. Conclusions: Anthropological reflections on the structure of human beings, which is activated or actualized in a special way in the face of death, can provide a framework for practice facing a humanization of medicine at the end of life, considering real experiences, possible needs, and underlying human conditions when facing end of life. The dimensions proposed can be taken into account in a sensitive way by supporting dialogues with dying people and their relatives. Trial registration: observational study.

Topic: Palliative Care and End-of-Life Issues
Subfield: Public Health, Environmental and Occupational Health
Field: Medicine
Domain: Health Sciences
Profiling of Phytochemical Compounds of East Java Red Rice Bran Has the High-Value Biological Activities as Antioxidant and Antidiabetic

The phytochemicals contained in rice bran, mainly flavonoid compounds, are predicted to have biological activity. Flavonoids are able to counteract the free radicals and degrade insulin resistance. The East Java Red Rice Bran samples, e.g., Mentik Wangi, Aek Sibundong, and Blambangan, were used in the study. Their phytochemical profiles, functional groups, antioxidant, and antidiabetic activities were investigated. The phytochemical analysis showed that the bran of Mentik Wangi, Aek Sibundong, and Blambangan contained flavonoid, triterpenoid, phenolic, tannin, and glycoside. Based on the FTIR, some functional groups were identified in three rice bran varieties, namely, the O-H stretching, C-H aliphatic, C-H sp3 stretching, C=C stretching aromatics, C=C stretching alkenes, CH2 and CH3 bonds rocking, C-H aromatic, CH-OH stretching alcohols, and C-O stretching ether or ester suggesting that rice brans are rich in phytochemical compounds. Through LC-HRMS analysis in positive ion mode, several types of flavonoids were confirmed. Pinocembrin was found in the three brands. The highest antioxidant and antidiabetic activity were observed in Blambangan rice bran with an IC50 value of 1.09 and 75.76 µg/mL, respectively. To conclude, the red rice bran phytochemical compounds exhibit potential biological activities as antioxidant and antidiabetic agents.

Topic: Phytochemicals and Antioxidant Activities
Subfield: Biochemistry
Field: Medicine
Domain: Health Sciences
The Effect of Load Deception on Kinetic Variables during the Second Pull from Blocks of the Power Clean

&lt;p&gt; Strength &amp; conditioning practitioners often seek novel and applied methods to enhance athletic performance. The purpose of this current research was to examine whether ‘not knowing the load ‘during a mid-thigh pull (MTP) performance led to enhanced performance characteristics across a randomised selection of loads (75%-95% 1RM). Fifteen male collegiate athletes (age 21.8 ± 2.3, height 171.8 ± 7.5 cm, mass 89.3kg ± 9.8kg, MTP 1RM 135.5kg ± 18kg) were selected for the pre 1RM MTP and the 5 post randomised unknown lifts between 75%-95% of individual 1RM. The research demonstrated that unknown loads at 75% 1RM lead to significant changes in average power (AP) (known1062±251 W, unknown1213 ± 289W; p ≤ 0.05; effect size (ES) = 0.56 small). Unknown loads at 75% 1RM lead to significant changes in average velocity (AV) (known: 0.49±0.1, unknown: 0.66 ± 0.10m/s; p ≤ 0.00; ES = 1.66 large). There was also a significant change in peak velocity (PV) at 75% 1RM (known: 0.74±0.16, unknown: 0.95 ± 0.26m/s; p ≤ 0.05; ES = 0.99 moderate). Unknown loads at 80% 1RM lead to significant changes in AV (known: 0.47±0.10 unknown: 0.60 ± 0.10m/s; p ≤ 0.01; ES = 1.36 large). There was no significant difference in AP, AV, peak power (PP) and PV variables across 85, 90, 95% 1RM (p ≥ 0.05; ES = trivial to small). It appears that these findings especially at unknown loads between 75% and 80% 1RM could be beneficial in enhancing velocity-based performance variables. Therefore, the applications of unknown loads are of meaningful practical use to enhance performance variables during weightlifting pulling derivatives. Therefore, weightlifting pulling derivatives are potentially a useful training modality to improve desirable ballistic actions in particular triple extension. &lt;/p&gt;

Topic: Sports Performance and Training
Subfield: Orthopedics and Sports Medicine
Field: Medicine
Domain: Health Sciences
Assembling Desire, Love and Affect in an Art Museum School

This chapter is comprised of desire, love and affective flows that passed through an emblematic art museum school as it was being shut down. Moving through this space are matters of power, race, belonging, loss and identity. Fueled by capacities of bodies to affect and be affected, the authors join in a second-person account of their experiences during the dissolution of the school based on Deleuze's concept of event. To one side of the event is past debris: the founding of the historic art museum school, and how its romantic ideals recently collided with political agendas and capital flows. On the other side of the event is the "yet to come," potential. Cramped between the two spaces is a desiring, art production of affective objects arranged around a gallery based on the theme of love–printed texts on postcards, audio recordings, love letters, dream telling, books about love–situated around a bed, a place of lovemaking, births, deaths and dreaming.

Topic: Art Education and Development
Subfield: Visual Arts and Performing Arts
Field: Arts and Humanities
Domain: Social Sciences
Forty-five Years of Dialogue Facilitation (1972–2017)

The aim of this article is to investigate how the Conference on Security and Cooperation in Europe ( csce ) succeeded in channelling the Cold War in a peaceful direction by facilitating a Pan-European dialogue during the second half of the Cold War (1972–1990), and what lessons we can learn from it today in terms of dialogue facilitation, so as to raise the profile of the Organization for Security and Cooperation in Europe and reduce international tensions. It is based on the hypothesis that the csce facilitated the ‘multilateralisation of European security’ through dialogue, and stabilised European relations by turning security into a joint venture. This article concludes with ten recommendations for facilitating dialogue through the osce so as to multilateralise European security again today.

Topic: European and Russian Geopolitical Military Strategies
Subfield: Political Science and International Relations
Field: Social Sciences
Domain: Social Sciences
Building an Online Grocery Business

This paper uses the case of ASDA.com, ASDA’s home-shopping arm, to demonstrate the challenges in building and developing an online grocery business in the UK. To set the stage, the initial implementation and learning from phone/catalogue home-shopping in ASDA is outlined to demonstrate why e-commerce was seen as most economically suitable to conduct a grocery home-shopping business. Then the paper illustrates the development stages and critical aspects of ASDA.com’s Web shop. Particularly, it delineates the operational aspects of B2C e-commerce in the grocery business: fulfillment center and fulfillment process. The case will also describe ASDA’s efforts in overcoming problems with their home-shopping fulfillment model and present important elements of ASDA.com’s virtual store and its operation. The paper concludes with the challenges that ASDA.com has been facing, their current status, and future prospects.

Topic: Consumer Retail Behavior Studies
Subfield: Marketing
Field: Business, Management and Accounting
Domain: Social Sciences
Serous adenocarcinoma detected in the cervical smear: A case report

Introduction. Cytological smear tests of the cervix are routine diagnostic methods used for detection of precancerous lesions and tumors of the cervix; they are highly sensitive and specific in the detection of precancerous squamous intraepithelial lesions. Glandular lesions are much less frequently found in the cervical smear. The most common glandular lesions detected in the cervical smear are endocervical and endometrial adenocarcinomas. Cervical metastases are rare, although there are case reports in the literature. Case Report. In this case report, we present a 64-year-old woman with an abnormal cervical smear and postmenopausal metrorrhagia. Numerous accumulations, as well as individual atypical epithelial cells, were detected in the cervical smear and a cytological diagnosis of a highgrade squamous intraepithelial lesion was made based on cytomorphological features suspicious for invasion (Bethesda Classification, 2014) so a cervical biopsy and curettage of the endocervical canal were performed. A high-grade serous adenocarcinoma was diagnosed by histopathological examination of cervical biopsy and cervical canal curettage specimens, after which a transvaginal ultrasound examination was performed, which showed tumors on both ovaries and free fluid in the abdominal cavity. The patient underwent abdominal hysterectomy with bilateral salpingo-oophorectomy. Histological examination confirmed high-grade ovarian papillary serous adenocarcinoma with psammoma bodies. Conclusion. The cytological diagnostic features and criteria for serous adenocarcinoma in Papanicolaou smears are still vague and insufficiently defined in the literature, which is the reason for very common errors in the interpretation, so further research on the pathogenesis, diagnosis and therapy of this tumor is of great importance.

Topic: Cervical Cancer and HPV Research
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Polluter-financed environmentally beneficial expenditures: Effective use or improper abuse of citizen suits under the Clean Water Act

In 1970, recognizing the cumbersome and often ineffective enforcement mechanisms in existing federal water and air pollution statutes, Congress passed the first citizen suit provision. This provision of the Clean Water Act was the subject of intense debate and underwent several transitions before it was finally adopted. With the advent of citizen suits in environmental legislation, Congress opened the courts to the public. Citizen suit provisions allowed private citizens to serve as watch-dogs of both industry and government, creating an additional check in the enforcement schemes established by Congress. But the provisions allowed only for enforcement, not for the right to sue for damages. The remedies available to citizen-plaintiffs were injunctive relief and, in the case of the Clean Water Act, civil penalties payable to the US Treasury. Focusing on the Clean Water Act, this Comment explores the use of alternative payments as settlement of Clean Water Act citizen suits: polluter-financed environmentally beneficial expenditures. As established through consent decrees, these expenditures go to local cleanup, research, and educational projects in the area of Clean Water Act violations, in lieu of or in addition to civil penalties. While the US Department of Justice has objected to the use of such settlements,more » one apellate court has ratified their use. This essay postulates that environmentally beneficial expenditures established through consent decrees are an important and effective use of the Clean Water Act's citizen suit provision, serving the dual goals of deterring polluters and mitigating the effects of past violations.« less

Topic: Environmental law and policy
Subfield: Law
Field: Social Sciences
Domain: Social Sciences
GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer

Abstract Although the Sonic hedgehog (SHH) signaling pathway has been implicated in promoting malignant phenotypes of prostate cancer, details on how it is activated and exerts its oncogenic role during prostate cancer development and progression is less clear. Here, we show that GLI3, a key SHH pathway effector, is transcriptionally upregulated during androgen deprivation and posttranslationally stabilized in prostate cancer cells by mutation of speckle-type POZ protein (SPOP). GLI3 is a substrate of SPOP-mediated proteasomal degradation in prostate cancer cells and prostate cancer driver mutations in SPOP abrogate GLI3 degradation. Functionally, GLI3 is necessary and sufficient for the growth and migration of androgen receptor (AR)–positive prostate cancer cells, particularly under androgen-depleted conditions. Importantly, we demonstrate that GLI3 physically interacts and functionally cooperates with AR to enrich an AR-dependent gene expression program leading to castration-resistant growth of xenografted prostate tumors. Finally, we identify an AR/GLI3 coregulated gene signature that is highly correlated with castration-resistant metastatic prostate cancer and predictive of disease recurrence. Together, these findings reveal that hyperactivated GLI3 promotes castration-resistant growth of prostate cancer and provide a rationale for therapeutic targeting of GLI3 in patients with castration-resistant prostate cancer (CRPC). Implications: We describe two clinically relevant mechanisms leading to hyperactivated GLI3 signaling and enhanced AR/GLI3 cross-talk, suggesting that GLI3-specific inhibitors might prove effective to block prostate cancer development or delay CRPC.

Topic: Hedgehog Signaling Pathway Studies
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Ototoxicity: etiology and issues.

Several classes of drugs have been identified as having ototoxic potential: aminoglycoside antibiotics, other basic antibiotics, antimalarial drugs, loop diuretics, and salicylates. Various chemicals have also been implicated in causing ototoxicity. If certain predisposing conditions are present when a potentially ototoxic drug is administered, the risk of ototoxicity is increased. These conditions include impaired renal functioning, pregnancy, previous or concomitant treatment with another potentially ototoxic drug, inherited susceptibility to ototoxicity, and the effects of noise. Other conditions that have been associated with ototoxicity for which there is a lack of strong scientific support are age, sex, and pre-existing hearing loss. The physician's awareness of predisposing conditions combined with rational drug usage can reduce ototoxic risk to the individual.

Topic: Hearing, Cochlea, Tinnitus, Genetics
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Changes in Some Parameters in Mixtures of Sainfoin with Subterranean Clover

Changes in some morphological and physiological parameters (leaves/stems ratio, total plastid pigments content, amount of fixed nitrogen) of sainfoin (Onobrychis Adans.) and subterranean clover (Trifolium subterraneum ssp.), pure grown and in mixtures in ratio 50:50% were studied in filed experiment in the Institute of Forage Crops, Pleven (2011-2015). Local population of sainfoin and three subspecies of subterranean clover, i.e. Trifolium subterraneum spp. brachycalicinum (cv. Antas), Trifolium subterraneum spp. yanninicum (cv. Trikkala) and Trifolium subterraneum spp. subterraneum (cv. Denmark) were used. Leaves/stems ratio of sainfoin in pure stands was 0.35 and it was found be enhanced in mixtures with Trifolium subterraneum spp. brachycalicinum (0.39) by 12.8%, and with Trifolium subterraneum spp. yanninicum (0.38) by 9.5%. Total plastid pigments in mixtures increased by 8.3% for Trifolium subterraneum spp. yanninicum spp. brachycalicinum and Trifolium subterraneum spp. yanninicum, and by 9.8% for Trifolium subterraneum spp. subterraneum, and decreased in sainfoin by 17.2% for mixture with Trifolium subterraneum spp. yanninicum. There were from 2.20 kg N/da (sainfoin + Trifolium subterraneum spp. subterraneum) to 2.88 kg N/da (sainfoin + Trifolium subterraneum spp. brachycalicinum) more fixed nitrogen in comparison to the amount fixed from pure grown sainfoin. Sainfoin and subterranean clover in mixtures showed good mutual tolerance, morphological and physiological status.

Topic: Agronomic Practices and Intercropping Systems
Subfield: Agronomy and Crop Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences