jimnoneill/paper-to-field-training huggingface dataset:
464 Anti-CTLA-4 therapy depletes Tregs and expands ICOS<sup>+</sup> T-cells in neuroblastoma tumors with induced DNA mismatch repair deficiency

<h3>Background</h3> Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) highly expressed on regulatory T-cells (Tregs) inhibit the activation of pro-inflammatory T-cells responsible for eliminating cancer cells. Anti-CTLA-4 can enhance T-cell activation by increasing CD28 co-stimulatory signaling through CTLA-4 blockade or depletion of Tregs by Fc-dependent effector mechanisms. Strategies to improve its therapeutic efficacy are needed as patient response rates to anti-CTLA-4 are low. Response to anti-CTLA-4 has been positively correlated with tumor mutation burden (TMB). Defects in the DNA mismatch repair (MMR) pathway can increase TMB and the production of neoantigens that promote anti-tumor immune responses. Here we investigate the underlying mechanism(s) to which induced MMR deficiency in an immunologically-cold and low TMB tumor model can enhance the therapeutic effect of anti-CTLA-4. We hypothesize that induced MMR deficiency in tumors enhances anti-CTLA-4-mediated Treg depletion and increases the infiltration and activation of effector T-cells. <h3>Methods</h3> MMR deficiency was induced in a syngeneic murine neuro-2a neuroblastoma cell line by knocking-out <i>MLH1</i> expression using CRISPR-Cas9. Wildtype MMR-proficient (pMMR) or induced MMR-deficient (idMMR) neuro-2a cells were inoculated into immunocompetent A/J mice and treated with anti-CTLA-4. Tumors were immunophenotyped by flow cytometry and mixed-lymphocyte reaction assays were used to examine the effects of MMR deficiency and anti-CTLA-4 on T-cell activation and proliferation. <h3>Results</h3> Induced MMR deficiency in neuroblastoma tumors enhances the anti-tumor immune response induced by anti-CTLA-4. MMR deficiency in neuroblastoma tumors promoted anti-CTLA-4-mediated Treg depletion and increased intratumoral CD3<sup>+</sup> T-cells. idMMR neuroblastoma tumors had an increase of ICOS<sup>+</sup> T-cells compared to pMMR tumors. In addition, ICOS<sup>+</sup> T-cells were increased further with anti-CTLA-4 treatment. <h3>Conclusions</h3> Our data show that inducing MMR deficiency in low TMB and immune-cold neuroblastoma tumors can enhance the anti-tumor effect of anti-CTLA-4 by increasing T-cell activation and depletion of Tregs. By understanding the underlying mechanism(s) of anti-CTLA-4 in idMMR tumors, it may justify targeting the MMR pathway to improve the response to immune checkpoint inhibitors in patients with immunologically-cold and/or low TMB tumors that are refractory to immunotherapy. Future studies will assess how inducing MMR deficiency alters the tumor microenvironment to enable anti-CTLA-4-mediated Treg depletion and the significance of ICOS<sup>+</sup> T-cells in the efficacy of anti-CTLA-4 therapy in this setting.

Topic: Neuroblastoma Research and Treatments
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Discrimination of wheat varieties by simultaneous measurements of oxygen consumption and consistency of flour dough during mixing

Abstract Using an instrumented mixing reactor, oxygen consumption and torque evolution were recorded during the mixing of wheat flour doughs from eight pure French wheat varieties harvested in 2002 and 2003. Wheat flours were also characterised by biochemical analyses including lipoxygenase (LOX) activity assay, free polyunsaturated fatty acid (PUFA) content, glutathione and ferulic acid contents, results of alveograph and farinograph tests and breadmaking performances. Some parameters defined from the obtained torque curves, equivalent to consistency curves, were correlated with alveograph and farinograph data. The importance of LOX activity levels and free PUFA content to explain the oxygen consumption during mixing is confirmed. In addition to the characteristics of the oxygen consumption curves, the extent to which the consistency curve parameters are able to differentiate among doughs made with flours from different wheat varieties is considered. Copyright © 2006 Society of Chemical Industry

Topic: Fermentation and Sensory Analysis
Subfield: Food Science
Field: Agricultural and Biological Sciences
Domain: Life Sciences
CLUEING IN: A GUIDE TO SOLVING THE PUZZLE OF SELF FOR WOMEN RECOVERING FROM DEPRESSION

Clueing in, a process constructed from data collected from women recovered or recovering from depression, seems to be a salient variable in reaching full recovery. While depression and its recovery are composed of a number of highly complex processes, when women clue in, or come to a cognitive and emotional realization of themselves in relation to their world, they seem able to put in place the final piece of the puzzle of who they are, that is, what is their true self. For women to reach full recovery, it seems necessary for them to discover the difference between what and who they are and are not responsible for in their lives. Clueing in is one component of a model of recovery developed from a grounded theory study conducted with 21 women during 1993 to 1995.

Topic: Counseling, Therapy, and Family Dynamics
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Global Political Science versus Critical Political Science

Given that critical reflection on politics is a core mission of political science, we might expect the geographic expansion of the discipline to bring a wave of critical consciousness of public affairs across the world. A tension has emerged, though, between a political science that is global and one that is critical. Sources of that tension lie in a universalizing tendency within the discipline, which squeezes out local conversations, and in the standardization of academic criteria that encourages faculty to engage external, “global” discussions rather than local ones. Political science knowledge, however critical in spirit, can end up disconnected from local engagement. The particular sort of global political science that has been created gives universities, departments, and faculty members reason to spread political science in a way that limits it as a mode of engaged inquiry. We should think carefully about how we can retain political science's critical edge as the profession globalizes.

Topic: Political Science Research and Education
Subfield: Political Science and International Relations
Field: Social Sciences
Domain: Social Sciences
Different underlying aetiologies in patients presenting with ventricular tachycardia fulfilling task force criteria for ARVC: initial suspicion based on the 12-lead electrocardiogram

Abstract Background The Task Force Criteria (TFC) for ARVC are highly sensitive, but lack specificity. Patients with atypical RV-involvement (aRVi) may have different underlying aetiologies and prognosis, requiring specific therapeutic interventions. Purpose We aimed to evaluate the role of the baseline ECG for initial suspicion of aRVi. Methods From the Netherlands Heart Institute Arrhythmogenic Cardiomyopathy (NHI-ACM) registry, patients were selected who 1) fulfilled TFC for definite ARVC, 2) presented with sustained VT, 3) underwent genetic testing. The first available ECG after VT was evaluated for AV-conduction and the presence and surface area (SA) of an R'-wave in V1-V3. ECGs with AV-conduction disturbances or an R'-wave with SA ≥1.65 mm2 were classified as suspicious for `atypical RV-involvement' (aRVi-ECG). Patients with ARVC-related pathogenic/likely pathogenic variant (P/LP+) were classified as “typical ARVC”. Data of patients without an ARVC-related pathogenic/likely pathogenic variant (P/LP−) were reviewed by an expert panel and classified as either “typical ARVC” or “suggestive for another aetiology” based on consensus. Results In total 124 P/LP+ patients and 35 P/LP− patients were included. Nineteen patients had an aRVi-ECG, which appeared significantly more predominant in the P/LP− group (11 (9%) P/LP+ vs. 8 (22%) P/LP−, p=0.019). Of the P/LP− patients, seventeen (49%) were classified as “suggestive for another aetiology” (e.g. myocarditis, ischemia, sarcoid), including all 8 patients with an aRVI-ECG. Among P/LP+ patients with an aRVi-ECG, 46% carried the Arg14del phospolamban variant and 64% died, versus 15% and 18% of P/LP+ patients without aRVi-ECG, respectively (Table 1). Conclusion For patients presenting with sustained VT and fulfilling the TFC for ARVC diagnosis, a baseline ECG suggestive for atypical RV-involvement should raise suspicion for a different underlying aetiology in patients without an ARVC-related P/LP variant. In P/LP+ patients, an aRVi-ECG may identify those with poor outcome. Funding Acknowledgement Type of funding sources: None.

Topic: Cardiovascular Effects of Exercise
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
The Numerical Analysis on Stability of Deep Roadway Support System

The effect of the roadway with no supporting and roadway that was reinforcement by rock bolts and anchor robs, anchor rod combined bolting shoring, anchor rod combined anchor rope and lining timbering was simulated by using numerical simulation software FLAC3D. The results showed that the deformation of no supporting roadway is maximal, and the maximal position is vault. The displacement of top floor and two side decreases after supported, which can reinforce surrounding rock. The reinforcement effect of the anchor rod combined anchor rope and lining timbering is best.

Topic: Geomechanics and Mining Engineering
Subfield: Mechanics of Materials
Field: Engineering
Domain: Physical Sciences
Re: Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer

No AccessJournal of UrologyUrological Survey1 Jan 2018Re: Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer David F. PensonMD, MPH David F. PensonDavid F. Penson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.09.104AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer." The Journal of Urology, 199(1), pp. 19–20 © 2018 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 199Issue 1January 2018Page: 19-20 Advertisement Copyright & Permissions© 2018 by American Urological Association Education and Research, Inc.MetricsAuthor Information David F. Penson More articles by this author Expand All Advertisement PDF downloadLoading ...

Topic: Hormonal and reproductive studies
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Neural Signatures of Trust in Reciprocity

Trust facilitates conditions for safe sharing of valued resources – a social setting vital to success in a wide range of socio-technological networks. With an increasing reliance of economic initiatives on trust-assured interactions, the need to inquire into the mental processes of trust has emerged. This led to a proliferation of functional magnetic resonance imaging (fMRI) studies focusing on domain-specific measures. However, inherent metric deficits of fMRI have resulted in discrete outcomes highlighting further need for constructing a comprehensive neurocognitive model of trust. Here, a domain-general methodology aims at overcoming the negative tendencies in prior fMRI studies by applying a series of coordinate-based “Activation Likelihood Estimation” (ALE) meta-analyses of the fMRI data and a data-driven Multivariate Granger Causality (MVGC) connectivity analysis of hyperscan-fMRI data – an approach not undertaken in trust studies prior to this dissertation. To determine the effects on behavior of cross-study variability in brain activation during a trust-inducing investment game (IG) task, the meta-analysis aims at revealing the extent of neurocognitive differentiation during trust, learning to trust and reciprocity. One-shot IG, implicating unconditional trust, is compared to multi-round IG implicating the conditional trust. In the MVGC study, the neurocognitive differences in the effective connectivity of interpersonal (“brain-to-brain”) trust are discerned. Meta-analysis revealed a strong differential response between unconditional trust (ambiguity, insula) and conditional trust (reward, ventral striatum). Learning to trust engaged a goal-guided (rostrolateral PFC) transition between decision-making (dorsal striatum, action-valuation) and feedback processing (ventral striatum, reward reinforcement). Reciprocating trust was linked to insula-mediated norm-compliance tendency to avoid breaking trust. For the effective connectivity analysis, a steady increase in trust and reciprocity engaged a mentalizing network as evidenced in the observed dorsal PFC connectivity with the parietal cortex. Within-trustor, dorsomedial (dmPFC) bidirectional connectivity with posterior cingulate cortex was key to guiding trust-valued choices (hypothalamus). Within-trustee, the key motive of norm-compliance – trustworthiness (lateral orbitofrontal cortex) was mediated by dorsomedial and dorsolateral PFC in Stage 1 and by precuneus in Stage 2. For the brain-to-brain exchange, the trustor’s dmPFC was most active, but the trustee’s dmPFC was virtually absent indicating dissociable patterns of other-regarding preferences for the trustor and trustee. Collectively, this dissertation lends evidence consistent with the putative socio-cognitive, economic-utility and reinforcement-learning models of trust and opens new perspectives by applying an effective domain-general data-driven dynamic approach.

Topic: Neural and Behavioral Psychology Studies
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Drug Courts: A Strategy for Managing Drug-Involved Offenders

Drug courts are a management strategy designed to use the authority of the courts to reduce crime by changing defendants' drug-using behavior. Drug-involved defendants are diverted to drug courts in exchange for the possibility of dismissed charges or reduced sentences. Judges preside over drug court proceedings and monitor the progress of the defendants. Working in collaboration with prosecutors, defense attorneys, treatment providers, probation agents, and others, judges proscribe sanctions for noncompliance with program requirements and rewards for compliance.

Topic: Opioid Use Disorder Treatment
Subfield: Public Health, Environmental and Occupational Health
Field: Medicine
Domain: Health Sciences
Applications of computer‐aided section construction, restoration, and balancing models to the petroleum industry

PreviousNext No AccessSEG Technical Program Expanded Abstracts 1989Applications of computer‐aided section construction, restoration, and balancing models to the petroleum industryAuthors: Roy KligfieldMark G. RowanR. RatliffRoy KligfieldUniversity of Colorado (UC) and Geo‐Logic Systems Inc. (GLS), Mark G. RowanUC and Alastair Beach Associates, Scotland, and R. RatliffUC and GLShttps://doi.org/10.1190/1.1889641 SectionsAboutPDF/ePub ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InRedditEmail Permalink: https://doi.org/10.1190/1.1889641FiguresReferencesRelatedDetails SEG Technical Program Expanded Abstracts 1989ISSN (print):1052-3812 ISSN (online):1949-4645Copyright: 1989 Pages: 1375 publication data© 1989 Copyright © 1989 Society of Exploration GeophysicistsPublisher:Society of Exploration Geophysicists HistoryPublished: 10 Feb 2005 CITATION INFORMATION Roy Kligfield, Mark G. Rowan, and R. Ratliff, (1989), "Applications of computer‐aided section construction, restoration, and balancing models to the petroleum industry," SEG Technical Program Expanded Abstracts : 589-589. https://doi.org/10.1190/1.1889641 Plain-Language Summary PDF DownloadLoading ...

Topic: Drilling and Well Engineering
Subfield: Ocean Engineering
Field: Engineering
Domain: Physical Sciences
Bipyridylacetylenes 1: the synthesis of some bipyridylacetylenes via the palladium-catalyzed coupling of acetylenes with 2,2′-dibromobipyridyl, and the single crystal X-ray structure of 6,6′-bisphenylethynyl-2,2′-bipyridine

The synthesis of a series of 6,6′-diethynyl-2,2′-bipyridyls from the palladium-catalyzed coupling of 6,6′-dibromo-2,2′-bipyridine with a series of arylacetylenes is reported. The single crystal X-ray structure of 6,6′-phenylethynyl-2,2′-bipyridyl was determined. Crystal data: monoclinic, A2/a, with cell constants a = 10.0385(4), b = 9.2166(4), c = 21.4130(8) Å, and β = 102.981(3)°; D calc . = 1.226 g cm −3 , Z = 4, R f = 0.045, S = 1.22, using 886 reflections of the 1443 unique reflections. The packing diagram indicates essentially that the molecules pack in a layered assembly with the nitrogen atoms of the dipyridyl groups on opposite sides and with a dihedral angle of 59.85(16)° between the pyridyl and phenyl groups. The acetylenic bond distances are normal. Key words: acetylene, palladium, catalysis, coupling, monomers, crystal structure.

Topic: Synthesis of heterocyclic compounds
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Spatio-temporal, optogenetic control of gene expression in organoids

Organoids derived from stem cells become increasingly important to study human development and to model disease. However, methods are needed to control and study spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics and gene perturbation technologies to activate or knock-down RNA of target genes, at single-cell resolution and in programmable spatio-temporal patterns. To illustrate the usefulness of our approach, we locally activated Sonic Hedgehog (<em>SHH</em>) signaling in an organoid model for human neurodevelopment. High-resolution spatial transcriptomic and single-cell analyses showed that this local induction was sufficient to generate stereotypically patterned organoids in three dimensions and revealed new insights into <em>SHH</em>’s contribution to gene regulation in neurodevelopment. With this study, we propose optogenetic perturbations in combination with spatial transcriptomics as a powerful technology to reprogram and study cell fates and tissue patterning in organoids.

Topic: Planarian Biology and Electrostimulation
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Integrated Active Learning Tools for Enhanced Pedagogy in a Software Engineering Course

Abstract Integrated Active Learning Tools for Enhanced Pedagogy in a Software Engineering CourseEffective teaching requires effective teaching tools. This pedagogical requirement is especiallyimportant for software engineering education where graduates are expected to develop softwarethat meets rigorous quality standards in functional and application domains. To enhancestudent's understanding of the needs of the professional software industry, lecture notes aresupplanted by additional pedagogical tools being developed at author's institution for a softwareverification and validation (V&V) course. These active learning teaching tools consisting ofclass exercises, case studies, and role play videos are being developed by partnering with theacademia and industry. The basic objectives of the project are to improve software education tomake it well aligned with academic research as well as industry best practices. This project isbeing funded through a NSF-TUES grant.Through this project twenty (20) delivery hours of lecture slides, eighteen (18) delivery hours ofcase studies, sixteen (16) delivery hours of exercises, and six (6) delivery hours of role playvideo totaling sixty (60) delivery hours of Software V&V course modules are being created. Inspring 2014 diverse case studies were delivered to Software Engineering juniors in the author'sinstitution and their learning outcomes tracked using a survey instrument. The results show thatthe students were able to better comprehend V&V topics like requirements engineering, reviewsand inspections, configuration management, and testing. The knowledge disseminated throughlectures seemed to be reinforced by the case studies. By spring 2015 more course materialsincluding teaching tools like exercises and role-play videos are expected to be created anddelivered. The results of this research work will be shared during the poster presentation atASEE. As part of the project dissemination plan the teaching materials will be made available tointerested institutions and professional organizations. An invitation only workshop is alsoplanned for August 2015 to share developed course materials and delivery mechanism.

Topic: Innovative Teaching Methods
Subfield: Education
Field: Social Sciences
Domain: Social Sciences
Risk of Ketosis During Intensive Insulin Therapy in Pre-School-Age Diabetic Children

The risk of ketosis and its relationship to the mode of insulin therapy were studied in a subset of pre-school-age diabetic children. These five children, who initially responded poorly to standard in-hospital diabetes management, were selected for a program of intensified therapy directed at achieving more stable blood glucose control. Optimized conventional therapy was first employed for 16 ± 5 mo and did not improve substantially blood glucose level or stability. During this period, there was an average of almost one episode of ketonuria per patient per month, and three diabetic ketoacidosis episodes were observed. Because of its limited efficacy, the treatment was then changed to continuous subcutaneous insulin infusion. This mode of therapy had a rapid favorable effect on blood glucose control, with no concomitant increase of the frequencies of ketonuria or diabetic ketoacidosis, most of which occurred during the first months of insulin pump therapy. Deliberate cessation of either conventional or subcutaneous insulin infusion therapy for 7 h under close in-hospital control resulted in similar metabolic changes: a slight nonconstant increase of blood glucose, and an abrupt rise of blood 3-hydroxybutyrate to 3 mM, with massive ketonuria. The management of these young diabetic children with insulin pump therapy was thus not associated with an increased frequency or an accelerated rate of development of ketosis. However, the possible failures originating from the infusing device and the rapid increase of ketosis in young ages require special vigilance from the parents, based on twice-daily urine testing for ketones and appropriate insulin supplementation.

Topic: Diabetes Management and Research
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
CCDC 643482: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Topic: Crystallization and Solubility Studies
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences