jimnoneill/paper-to-field-training huggingface dataset:
A Quantitative Systems Pharmacology Computer Model for Schizophrenia Efficacy and Extrapyramidal Side Effects

Abstract Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I‐III Regulatory, Quality, Manufacturing Postmarketing Phase IV Despite tremendous advances in understanding the neurobiology of schizophrenia, no real therapeutic breakthrough in terms of novel antipsychotics has been made since the serendipitous discovery of chlorpromazine. We describe a computer‐based mechanistic disease simulation model of biophysically realistic neurons that captures most of the subcortical neuromodulatory processes important in the pathophysiology of schizophrenia and calibrate this with a large retrospective clinical database for Positive and Negative Symptoms Scale in Schizophrenia ( PANSS total) and extrapyramidal symptoms ( EPS ) liability. Additionally we make this platform more actionable for practical use in central nervous system drug discovery by introducing a synaptic receptor competition model that accurately captures clinical target exposures. The model accounts for threefold more variance than the simple dopamine D 2 receptor occupancy rule and is also superior in a number of independent clinical data sets. As such, the model is a first step in a better understanding of the human neurobiology of schizophrenia. Using human pharmacology and a positron emission tomography target engagement study as input, the model can estimate a value for the clinical efficacy on PANSS total and EPS side effect liability for the clinical doses of a new investigative compound. This Quantitative Systems Pharmacology platform, by simulating the effect of co‐medications and genotypes in a clinical setting, represents a useful addition to psychiatric drug discovery efforts.

Topic: Treatment of Major Depression
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Through Lines: Exploring Past/Present Connections in Middle Grade Novels

Abstract Recently, the public outcry after the death of George Floyd at the hands of Minneapolis police revealed a disconnect among some Americans between historical events (slavery, the Civil Rights movement) and the present day. That is, many Americans—particularly White Americans—had believed racism to be a mostly historical construct and failed to understand the ways in which past societal structures continue to influence racial inequities today. This article explores the use of historical and modern novel pairs to bridge gaps in understanding for middle grade readers. Reading high‐quality, culturally authentic books such as Esperanza Rising (Ryan, 2000) and Return to Sender (Alvarez, 2009) can help students recognize the systemic nature of racism and critically consider ways in which they can use their own voices to disrupt it. Included in this piece are instructional ideas and multiple novel pair suggestions.

Topic: Educator Training and Historical Pedagogy
Subfield: Sociology and Political Science
Field: Social Sciences
Domain: Social Sciences
Therapeutic time window for angiotensin‐(1–7) in acute lung injury

Background and Purpose There is presently no proven pharmacological therapy for the acute respiratory distress syndrome. Recently, we and others discovered that the heptapeptide angiotensin‐(1–7) [Ang‐(1–7)] shows significant beneficial effects in preclinical models of acute lung injury (ALI). Here, we aimed to identify the best time window for Ang‐(1–7) administration to protect rats from oleic acid (OA) induced ALI. Experimental Approach The effects of i.v. infused Ang‐(1–7) were examined over four different time windows before or after induction of ALI in male Sprague–Dawley rats. Haemodynamic effects were continuously monitored, and loss of barrier function, inflammation and lung peptidase activities were measured as experimental endpoints. Key Results Ang‐(1–7) infusion provided the best protection against experimental ALI when administered by continuous infusion starting immediately after 30 min OA infusion till the end of the experiment (30–240 min). Both pretreatment (−60 to 0 min before OA) and short‐term therapy (30–90 min) also had beneficial effects although less pronounced than the effects achieved with the optimal therapy window. Starting infusion of Ang‐(1–7) 60 min after the end of OA treatment (90–240 min) did not protect barrier function or haemodynamics but still reduced myeloperoxidase activity and increased ACE2/ACE activity ratio respectively. Conclusions and Implications Our findings indicate that early initiation of therapy after ALI and continuous drug delivery are most beneficial for optimal therapeutic efficiency of Ang‐(1–7) treatment in experimental ALI and, presumably accordingly, in clinical acute respiratory distress syndrome.

Topic: Respiratory Support and Mechanisms
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Integrated Analysis of Small RNA, Transcriptome, and Degradome Sequencing Reveals the MiR156, MiR5488 and MiR399 Are Involved in the Regulation of Male Sterility in PTGMS Rice

A photoperiod- and thermo-sensitive genic male sterile (PTGMS) line is the basic material for two-hybrid rice and is an important genetic breeding resource. Peiai64S (PA64S) is an important germplasm resource of PTGMS rice, and it has been applied to two-line hybrid rice systems in China. Pollen fertility in PA64S is regulated by the temperature and photoperiod, but the mechanism of the fertility transition is unclear. In this study, we obtained the male fertile plant PA64S(F) and the male sterile plant PA64S(S) by controlling different temperatures under long light conditions and used the male fertile and sterile plants to investigate the role of microRNAs (miRNAs) in regulating male fertility in rice. We performed the small RNA library sequencing of anthers from PA64S(S) and PA64S(F). A total of 196 miRNAs were identified—166 known miRNAs among 27 miRNA families and 30 novel miRNAs. In the transcriptome analysis, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes revealed significant enrichment in the synthesis and metabolism of fatty acids and some secondary metabolism pathways such as fatty acid metabolism and phenylalanine metabolism. With a comprehensive analysis of miRNA, transcriptome, and degradome sequencing, we identified that 13 pairs of miRNA/target genes regulated male fertility in rice by responding to temperature change, among which the miR156, miR5488, and miR399 affect the male fertility of PA64S by influencing SPLs, the lignin synthesis of anther walls, and the flavonoid metabolism pathway. The results provide a new understanding of PTGMS rice, which will help us better understand the potential regulatory mechanisms of male sterility in the future.

Topic: Plant Molecular Biology Research
Subfield: Plant Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Atelectasis: An Uncommon Sign of Achalasia in Childhoo

An 11-year-old boy presented to our pediatric pulmonology clinic with a 3-month history of atelectasis evident on his chest radiography. Breath sounds revealed fine crackles in the right lower zone and rhonchi in the upper zones. His initial pulmonary function test was compatible with restrictive pulmonary disease. Chest tomography revealed that the trachea, right intermediate, and middle lobe bronchi were narrowed by megaesophagus. Esophagogram determined dilatation of the esophagus and “bird-beak” sign in the esophagogastric junction but it was not sufficient to diagnose. Esophageal manometry which is the gold standard test for achalasia was performed and type 2 achalasia was diagnosed. His symptoms improved following Heller myotomy conducted together with Dor fundoplication. Although respiratory problems are more common in infants and younger children, atypical respiratory presentations may also occur during adolescence. Achalasia should be one of the rare differential diagnoses of pediatric restrictive pulmonary disease.

Topic: Tracheal and airway disorders
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Clip thinking in the digital age: complementary or contradictory

This paper explores the concept of "Clip Thinking" in the context of the digital age and investigates whether it is a complimentary or contradictory approach. Clip Thinking refers to the tendency of individuals to consume information and ideas in short, fragmented, and easily digestible formats, often facilitated by social media platforms and digital technologies. While Clip Thinking offers benefits such as quick access to diverse perspectives and efficient information processing, it also raises concerns about shallow engagement, echo chambers, and reduced critical thinking skills. This study employs a mixed-methods approach, combining qualitative interviews and quantitative surveys, to gather insights from participants representing different age groups, educational backgrounds, and digital media consumption habits. The qualitative interviews delve into participants' motivations, habits, and experiences related to Clip Thinking, providing an in-depth understanding of the phenomenon. The quantitative surveys measure participants' information consumption patterns, cognitive abilities, and attitudes towards Clip Thinking. On one hand, participants appreciate the convenience and accessibility offered by short, clipped content. They find it easier to navigate the overwhelming information landscape, rapidly browse topics of interest, and connect with a broader range of ideas. On the other hand, concerns emerge regarding the potential for information overload, reduced attention spans, and a lack of depth in understanding complex issues. Participants express worries about the erosion of critical thinking skills and the creation of filter bubbles that reinforce pre-existing beliefs. By analyzing the data collected, this paper aims to provide a nuanced understanding of the impacts of Clip Thinking on individuals' cognitive processes, decision-making abilities, and overall information consumption habits. The study's conclusions will inform educators, policymakers, and media platforms about the challenges and opportunities associated with promoting a balanced information ecosystem in the digital age.

Topic: Knowledge Management and Sharing
Subfield: Communication
Field: Social Sciences
Domain: Social Sciences
The reactivity of Cymbidium hybridum protocorm-like bodys vitrocultivated in liquid medium, depleted in microelements

The nature of the chemical compounds, the proportion and concentration in mineral elements, as part of the culture medium’s preparation, they influence the growth and the morphogenesis of clones. Starting from these premise, we proposed ourselves to study the Cymbidium hybridum protocorms reactivity, in the cultivation conditions of those in submersing regime in liquid medium Murashige-Skoog (1962) (MS) [14], with a complete set of mineral elements, or damaged in one of those microelements as B, Mn, Zn, Mo, Cu, Co or I. Those culture medium contained or not various growth hormones. After 90 days from inoculation, the most proliferative intense processes of the protocorms, we have registered in the practiced vitrocultures without iodine microelement, but in the presence of BA (2 mg/l) in the liquid medium, as a unique growth regulator (reference lot, considered 100%), the registered increases were 600% in the protocorms multiplication. The absence of iodine in the culture medium has determined the increase of the fresh and dry weight of the protocorms’ biomass, regardless the growth hormones content in the substratum, except the medium with 2 mg/l 2,4-D, from which, the performed observations made after 30 days from the experiment’s montage, were noticed senescence processes.

Topic: Plant tissue culture and regeneration
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Housing tenure of young people through a multilevel strategy: differences according to living arrangements

In this study, we identify and analyse the key determinants of the housing tenure regime and residential independence of young adults in Spain. We use a multilevel strategy that allows us to take into account the heterogeneity amongst regions in both homeownership rate and residential independence rate. Our focus is on young adults as this group have a significant effect on the real estate market. Furthermore, young adults are at an age in their life cycle when important events occur. The results show that demographic factors are more important than economic factors in both processes. Also, for these young adults, the sociocultural norms of each region are not the main criteria in housing tenure and residential independence. Given the recent changes seen in the type of cohabitation, we also analyse the housing tenure for different groups of young adults according to their living arrangements (alone, married couple or common-law couple). For young adults living alone, we find there is little variability among regions. Differences are seen in the factors that influence homeownership among young adults who have formalized their union through marriage and those who are part of a common-law couple.

Topic: Migration, Aging, and Tourism Studies
Subfield: Demography
Field: Social Sciences
Domain: Social Sciences
MOETA: a novel text-mining model for collecting and analysing competitive intelligence

The internet constitutes a vast repository of textual information, and its emergence has dramatically changed the environment in which businesses operate. Its development has had a great influence on the current business models. The goal of this work is to outline a novel text-mining-based decision-support model, Mining for Opinion, Event and Timeline Analysis (MOETA), which aims to explore competitive intelligence from the internet and the internal textual data sources of a company in depth. MOETA integrates novel Natural Language Processing (NLP) technologies for event detection and opinion mining to locate events and opinions on a timeline. The aim is to distil unstructured textual data into knowledge and intelligence that are useful to business decision-makers. An overview of the model is given and the architecture of a system based on the model is introduced. Moreover, we provide a practical example to explain how MOETA can support decision making.

Topic: Advanced Text Analysis Techniques
Subfield: Artificial Intelligence
Field: Computer Science
Domain: Physical Sciences
The Supply of Glass at <i>Portus Ilicitanus</i> (Alicante, Spain): A Meta‐Analysis of HIMT Glasses

Portus Ilicitanus (Picola, Alicante) was the main sea harbour of the Roman Colonia Iulia Ilici Augusta and as such played a crucial role in the supply of fundamental commodities to the Iberian Peninsula. Excavations yielded large quantities of glass in fourth‐ and early fifth‐century contexts. Elemental analysis of 60 samples by laser ablation – inductively coupled plasma – mass spectrometry (LA–ICP–MS) confirmed that the glasses were imported from the Eastern Mediterranean. A majority of the glasses correspond to the HIMTa primary production group, which originates from Egypt. The statistical evaluation of published data of 589 HIMT glasses further revealed differential distribution patterns of the HIMTa and HIMTb subtypes between the Eastern and Western Mediterranean, suggesting chronological trends that are linked to wider geopolitical changes. This demonstrates the need for systematic large‐scale approaches to identify supply patterns and possible factors underlying geographical differences and/or chronological developments.

Topic: Cultural Heritage Materials Analysis
Subfield: Archeology
Field: Arts and Humanities
Domain: Social Sciences
Supplementary Table 2 from Maximizing the Efficacy of MAPK-Targeted Treatment in &lt;i&gt;PTEN&lt;/i&gt;&lt;sup&gt;LOF&lt;/sup&gt;&lt;i&gt;/BRAF&lt;/i&gt;&lt;sup&gt;MUT&lt;/sup&gt; Melanoma through PI3K and IGF1R Inhibition

&lt;p&gt;PI3Kβi (rac-KIN-193) treatment induces the interaction of p85 with a panel of proteins in &lt;i&gt;PTEN&lt;sup&gt;LOF&lt;/sup&gt;&lt;/i&gt;/&lt;i&gt;BRAF&lt;sup&gt;MUT&lt;/sup&gt;&lt;/i&gt; melanoma. RVH-421 were treated with DMSO or 1μM PI3Kβi for 2h. Lysates were subjected to immunoprecipitation using an antibody targeting p85. Proteins in the range of 75 to 250 kDa were identified by LC-MS as described. Total spectra counts were used as a measure for protein quantity. The table summarizes the proteins enriched upon PI3Kβi treatment in the p85 precipitate. A spectral count ratio of 4 (log&lt;sub&gt;2&lt;/sub&gt; (PI3Kβi /DMSO) &gt; 2) was taken as an arbitrary cutoff for significant enrichment.&lt;/p&gt;

Topic: Melanoma and MAPK Pathways
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Optimal Protection of Property Rights in a General Equilibrium Model of Growth*

Abstract We incorporate weak property rights into an otherwise standard general equilibrium model of growth and second‐best optimal policy. In this setup, the state plays two of its key roles: it protects property rights and provides public services. The government chooses policy (the income tax rate, as well as the allocation of collected tax revenues between law enforcement and public services) to maximize the growth rate of the economy. The focus of our analysis is on how weak property rights generate multiple decentralized competitive equilibria, the different properties of these equilibria, and the implications of second‐best optimal policies.

Topic: Fiscal Policy and Economic Growth
Subfield: Economics and Econometrics
Field: Economics, Econometrics and Finance
Domain: Social Sciences
A NEW CARABUS AND CYCHRUS, WITH MISCELLANEOUS NOTES ON COLEOPTERA

Among a large series of Coleoptera collected by Mr. C.H. T. Townsend in the northwestern part of Mexico and forwarded to some years ago, I not an interesting new Carabus, which may be described as follows:- Carabus Townsendi , n. sp.—Somewhat similar to Forreri, Bates— Ann. &amp; Mag., N. Hist, ser. 5 IX, p.320— from Durango, but narrower in form, the elytra having similarly close-set unimpressed series of very minute punctures but having each only two sereis of larger, widely-spaced, impressed foveæ, the inner of the three series of Forreri being wholly absolete, the middle series only present in basal half and the outer extending only to apical fourth, the lateral margin more narrowly reflexed and with bluish reflection. Length, 21 mm.; width, 9 mm.

Topic: Scarabaeidae Beetle Taxonomy and Biogeography
Subfield: Paleontology
Field: Earth and Planetary Sciences
Domain: Physical Sciences
Biological aspects of the banana moth

The goal of this study was to develop a technique of rearing the Opogona sacchari (Bojer) (Lepidoptera: Lyonetdae). The experiment was conducted at the Entomology Laboratory of Epagri/Experiment Staton of Itajaí, SC Brazil. The larvae were reared in natural diet: agar (25g), distlled water (500ml), pulp of green banana (500g), methylis parahydroxibenzoas (0.550g), sorbic acid (1.5g) and streptomicina (0,1g). The couples were placed in PVC cages where the females laid their eggs. The incubaton period of the eggs varied from 4 to 7 days. The average duraton of the larval and pupal phases was 25.3 and12.7 days respectvely. The egg-adult period varied from 32 to 41 days. The average lifetme of the female was 10.5 days, and that of the male was 8.3 days. The rearing technique proved adequate for the study of diﬀerent stages of life cycle and can be enhanced to improve the viability of the larval and pupal phases.

Topic: Banana Cultivation and Research
Subfield: Plant Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
Conceptions of Learning in Technology-Enhanced Learning Environments

Studies about students' conceptions of learning have received much attention among educators, as these conceptions may guide students' learning processes and then outcomes. Research evidence also indicates that these conceptions are related to the learning context or environment under investigation. In this talk, I will share a series of studies investigating students' conceptions of learning in technology-enhanced learning environments. The studies cover students' conceptions of web-based learning, ubiquitous learning and learning by online peer assessment. The relationships between these conceptions of learning and their approaches to learning are also addressed in this talk.

Topic: Online and Blended Learning
Subfield: Education
Field: Social Sciences
Domain: Social Sciences
Generalized Tate curve and integral Teichmüller modular forms

In this paper, we establish a higher genus version of the Tate (elliptic) curve, i.e., for a given degenerate curve, we construct its universal deformation defined over the ring of formal power series of certain deformation parameters whose coefficients are in a finitely generated z-algebra described by the dual graph of the degenerate curve. Further, we study automorphic forms on the moduli space of algebraic curves (which we call Teichmüller modular forms) by evaluating these forms on the generalized Tate curve. In particular, we show that integral Teichmüller modular forms of given degree make a finitely generated ring, and we describe the structure of this ring in degree 2 and 3 cases.

Topic: Algebraic Geometry and Number Theory
Subfield: Geometry and Topology
Field: Mathematics
Domain: Physical Sciences
Some Results on a Fully Nonlinear Equation in Conformal Geometry

In this thesis we study the question of solving an equation arising in conformal geometry. Specifically, we obtain information about the equation σk(g Ag) = constant. Here g is a metric in a given conformal class [g0] and Ag is the Schouten tensor of g. First, we generalize a result of Chang, Gursky, and Yang to show that under certain geometric conditions, entire solutions of this equation on R must necessarily arise via pullback from the sphere under stereographic projection. This “Obata” type theorem provides an alternate proof of a result of Li and Li. However, our approach uses integral estimates which may be more amenable to application on manifolds which are not locally conformally flat. Second, we study the question of solving σk = constant on n-manifolds M , the “σk-Yamabe problem”, when k = 2 and n = 3. The σk-Yamabe problem has been studied for many values of n and k before (by Li and Li, by Guan and Wang, by Gursky and Viaclovsky, by Sheng, Trudinger, and Wang, and by Trudinger and Wang, among others); however, some cases remain open. The case where n > 2k is unresolved in general. A perhaps more natural question to consider in this case is solving v2k = constant, for n > 2k, where v2k are the renormalized volume coefficients studied by Graham and by Chang and Fang. Unfortunately, the approach used for other values of n and k does not apply in this final case–for v2k, one cannot use the local estimates of Guan and Wang and of Chen. This is because the local estimates use algebraic properties of σk which do not hold for v2k. Though the σ2-Yamabe problem in dimension 3 has been studied before, we study an alternative approach which avoids the use of the local estimates. We hope this approach may prove useful for resolving the question of solving v2k = constant.

Topic: Geometric Analysis and Curvature Flows
Subfield: Applied Mathematics
Field: Mathematics
Domain: Physical Sciences