Classical Logical versus Quantum Conceptual Thought: Examples in Economics, Decision theory and Concept Theory

Inspired by a quantum mechanical formalism to model concepts and their disjunctions and conjunctions, we put forward in this paper a specific hypothesis. Namely that within human thought two superposed layers can be distinguished: (i) a layer given form by an underlying classical deterministic process, incorporating essentially logical thought and its indeterministic version modeled by classical probability theory; (ii) a layer given form under influence of the totality of the surrounding conceptual landscape, where the different concepts figure as individual entities rather than (logical) combinations of others, with measurable quantities such as 'typicality', 'membership', 'representativeness', 'similarity', 'applicability', 'preference' or 'utility' carrying the influences. We call the process in this second layer 'quantum conceptual thought', which is indeterministic in essence, and contains holistic aspects, but is equally well, although very differently, organized than logical thought. A substantial part of the 'quantum conceptual thought process' can be modeled by quantum mechanical probabilistic and mathematical structures. We consider examples of three specific domains of research where the effects of the presence of quantum conceptual thought and its deviations from classical logical thought have been noticed and studied, i.e. economics, decision theory, and concept theories and which provide experimental evidence for our hypothesis.Comment: 14 page

Quantum Experimental Data in Psychology and Economics

We prove a theorem which shows that a collection of experimental data of probabilistic weights related to decisions with respect to situations and their disjunction cannot be modeled within a classical probabilistic weight structure in case the experimental data contain the effect referred to as the 'disjunction effect' in psychology. We identify different experimental situations in psychology, more specifically in concept theory and in decision theory, and in economics (namely situations where Savage's Sure-Thing Principle is violated) where the disjunction effect appears and we point out the common nature of the effect. We analyze how our theorem constitutes a no-go theorem for classical probabilistic weight structures for common experimental data when the disjunction effect is affecting the values of these data. We put forward a simple geometric criterion that reveals the non classicality of the considered probabilistic weights and we illustrate our geometrical criterion by means of experimentally measured membership weights of items with respect to pairs of concepts and their disjunctions. The violation of the classical probabilistic weight structure is very analogous to the violation of the well-known Bell inequalities studied in quantum mechanics. The no-go theorem we prove in the present article with respect to the collection of experimental data we consider has a status analogous to the well known no-go theorems for hidden variable theories in quantum mechanics with respect to experimental data obtained in quantum laboratories. For this reason our analysis puts forward a strong argument in favor of the validity of using a quantum formalism for modeling the considered psychological experimental data as considered in this paper.Comment: 15 pages, 4 figure

Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.

PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosing with class I PI3K inhibitor pictilisib (GDC-0941). These candidate metabolomics biomarkers were evaluated in a phase I dose-escalation clinical trial of pictilisib. Time- and dose-dependent effects were observed in patients for 22 plasma metabolites. The changes exceeded baseline variability, resolved after drug washout, and were recapitulated on continuous dosing. Our study provides a link between modulation of the PI3K pathway and changes in the plasma metabolome and demonstrates that plasma metabolomics is a feasible and promising strategy for biomarker evaluation. Also, our findings provide additional support for an association between insulin resistance, branched-chain amino acids, and related metabolites following PI3K inhibition. Mol Cancer Ther; 15(6); 1412-24. ©2016 AACR.The Institute of Cancer ResearchThis is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/1535-7163.MCT-15-081

The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma.

CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently inhibited cellular CHK1 activity (IC50 30-220 nM) and enhanced gemcitabine and SN38 cytotoxicity in multiple human tumor cell lines and human tumor xenograft models. Mouse oral bioavailability was complete (100%) with extensive tumor exposure. Genotoxic-induced CHK1 activity (pS296 CHK1) and cell cycle arrest (pY15 CDK1) were inhibited both in vitro and in human tumor xenografts by CCT245737, causing increased DNA damage and apoptosis. Uniquely, we show CCT245737 enhanced gemcitabine antitumor activity to a greater degree than for higher doses of either agent alone, without increasing toxicity, indicating a true therapeutic advantage for this combination. Furthermore, development of a novel ELISA assay for pS296 CHK1 autophosphorylation, allowed the quantitative measurement of target inhibition in a RAS mutant human tumor xenograft of NSCLC at efficacious doses of CCT245737. Finally, CCT245737 also showed significant single-agent activity against a MYC-driven mouse model of B-cell lymphoma. In conclusion, CCT245737 is a new CHK1 inhibitor clinical development candidate scheduled for a first in man Phase I clinical trial, that will use the novel pS296 CHK1 ELISA to monitor target inhibition

Research misconduct in the fields of ethics and philosophy: researchers’ perceptions in Spain

This is the Author’s Original Manuscript (AOM) (also called a “preprint”) sent to review to Science and Engineering Ethics on 11/10/2020. The final version of the article was published online at SEE on 21/01/2021. The online version is available at: https://doi.org/10.1007/s11948-021-00278-wEmpirical studies have revealed a disturbing prevalence of research misconduct in a wide variety of disciplines, although not, to date, in the areas of ethics and philosophy. This study aims to provide empirical evidence on perceptions of how serious a problem research misconduct is in these two disciplines in Spain, particularly regarding the effects that the model used to evaluate academics’ research performance may have on their ethical behaviour. The methodological triangulation applied in the study combines a questionnaire, a debate at the annual meeting of scientific association, and in-depth interviews. Of the 541 questionnaires sent out, 201 responses were obtained (37.1% of the total sample), with a significant difference in the participation of researchers in philosophy (30.5%) and in ethics (52.8%); 26 researchers took part in the debate and 14 interviews were conducted. The questionnaire results reveal that 91.5% of the respondents considered research misconduct to be on the rise; 63.2% considered at least three of the fraudulent practices referred to in the study to be commonplace, and 84.1% identified two or more such practices. The researchers perceived a high prevalence of duplicate publication (66.5%) and self-plagiarism (59.0%), use of personal influence (57.5%) and citation manipulation (44.0%), in contrast to a low perceived incidence of data falsification or fabrication (10.0%). The debate and the interviews corroborated these data. Researchers associated the spread of these misconducts with the research evaluation model applied in Spain

Single-level anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cage and allograft bone

BACKGROUND: In an effort to avoid the morbidity associated with autogenous bone graft harvesting, cervical cages in combination with allograft bone are used to achieve fusion. The goal of the current study was to assess the reliability and efficacy of anterior cervical discectomy and interbody fusion (ACDF) using a PEEK anatomical cervical cage in the treatment of patients affected by single-level cervical degenerative disease. METHODS AND MATERIALS: Twenty-five patients affected by single-level cervical degenerative pathology between C4 and C7 were enrolled in this study. The clinical findings were assessed using the Neck Disability Index and the Visual Analog Scale. Surgical outcomes were rated according to Odom's criteria at last follow-up. Fusion was graded as poor, average, good or excellent by assessing the radiographs. Cervical spine alignment was evaluated by sagittal segmental alignment and sagittal alignment of the whole cervical spine preoperatively, 6 months postoperatively and at the last follow-up. RESULTS: Twenty-five patients underwent ACDF using a PEEK anatomical cervical cage. All patients had a minimum 2 years of follow-up. The operative levels were C4-C5 in 5 patients, C5-C6 in 12 patients and C6-C7 in 8 patients. Preoperatively, average NDI was 34, 13 at 6 months, and 10 at latest follow-up. The mean preoperative VAS was 7; the mean postoperative VAS at latest follow-up was 3. Good or excellent fusion was achieved in all patients within 10 months (mean 5 months). Preoperatively, average sagittal segmental alignment (SSA) was 0.2\ub0 and average sagittal alignment of the cervical spine (SACS) 15.8\ub0. Six months after surgery, average SSA was 1.8\ub0 and average SACS 20.9\ub0, and at last follow-up, average SSA was 1.6\ub0 and average SACS 18.5\ub0. CONCLUSION: Anterior cervical discectomy and interbody fusion using PEEK anatomical cervical cages can be considered a safe and effective technique to cure cervical disc herniation with intractable pain or neural deficit in cases where conservative treatment failed

Determinants on an efficient cellulase recycling process for the production of bioethanol from recycled paper sludge under high solid loadings

Background: In spite of the continuous efforts and investments in the last decades, lignocellulosic ethanol is still not economically competitive with fossil fuels. Optimization is still required in different parts of the process. Namely, the cost effective usage of enzymes has been pursued by different strategies, one of them being recycling. Results: Cellulase recycling was analyzed on Recycled Paper Sludge (RPS) conversion into bioethanol under intensified conditions. Different cocktails were studied regarding thermostability, hydrolysis efficiency, distribution in the multiphasic system and recovery from solid. Celluclast showed inferior stability at higher temperatures (45-55 ºC), nevertheless its performance at moderate temperatures (40ºC) was slightly superior to other cocktails (ACCELLERASE®1500 and Cellic®CTec2). Celluclast distribution in the solid-liquid medium was also more favorable, enabling to recover 88 % of final activity at the end of the process. A Central Composite Design studied the influence of solids concentration and enzyme dosage on RPS conversion by Celluclast. Solids concentration showed a significant positive effect on glucose production, no major limitations being found from utilizing high amounts of solids under the studied conditions. Increasing enzyme loading from 20 to 30 FPU/ gcellulose had no significant effect on sugars production, suggesting that 22 % solids and 20 FPU/gcellulose are the best operational conditions towards an intensified process. Applying these, a system of multiple rounds of hydrolysis with enzyme recycling was implemented, allowing to maintain steady levels of enzyme activity with only 50 % of enzyme on each recycling stage. Additionally, interesting levels of solid conversion (70-81 %) were also achieved, leading to considerable improvements on glucose and ethanol production comparatively with the reports available so far (3.4 and 3.8 fold, respectively). Conclusions: Enzyme recycling viability depends on enzyme distribution between the solid and liquid phases at the end of hydrolysis, as well as enzymes thermostability. Both are critical features to be observed for a judicious choice of enzyme cocktail. This work demonstrates that enzyme recycling in intensified biomass degradation can be achieved through simple means. The process is possibly much more effective at larger scale, hence novel enzyme formulations favoring this possibility should be developed for industrial usage.This work had the fnancial support of the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/ BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the MultiBiorefnery project (POCI-01-0145-FEDER-016403). Furthermore, FCT equally supported the Ph.D. grant to DG (SFRH/BD/88623/2012).info:eu-repo/semantics/publishedVersio

Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice