The Geography of Non-formal Manifolds

We show that there exist non-formal compact oriented manifolds of dimension $n$ and with first Betti number $b_1=b\geq 0$ if and only if $n\geq 3$ and $b\geq 2$, or $n\geq (7-2b)$ and $0\leq b\leq 2$. Moreover, we present explicit examples for each one of these cases.Comment: 8 pages, one reference update

From Imitation to Collusion: Long-run Learning in a Low-Information Environment

We study long-run learning in an experimental Cournot game with no explicit information about the payoff function. Subjects see only the quantities and payoffs of each oligopolist after every period. In line with theoretical predictions and previous experimental findings, duopolies and triopolies both reach highly competitive levels, with price approaching marginal cost within 50 periods. Using the new ConG software, we extend the horizon to 1,200 periods, far beyond that previously investigated. Already after 100 periods we observe a qualitative change in behavior, and quantity choices start to drop. Without pausing at the Cournot-Nash level quantities continue to drop, eventually reaching almost fully collusive levels in duopolies and often reaching deep into collusive territory for triopolies. Fitted models of individual adjustment suggest that subjects switch from imitation of the most profitable rival to other behavior that, intentionally or otherwise, facilitates collusion via effective punishment and forgiveness. Remarkably, subjects never learn the best-reply correspondence of the one-shot game. Our results suggest a new explanation for the emergence of cooperation

Interactive Exploration of Chemical Space with Scaffold Hunter

The supporting information is composed of the following files: I. pyruvatekinasedata.zip The pyruvate kinase data set used for the analysis described in the referenced publication is contained in this file. The analysis is based on the Pyruvate Kinase Screen as published in PubChem under the assay ID 361. It contains all compounds checked in this screen together with the scaffold tree generated from it. Scaffold Hunter can be used to query the database and interactively display the scaffold tree. This file is a dump from a MySQL 5.1 database and was generated with MySQL Administrator 1.2.5. It can be restored with the same program. II. scaffoldhunter_profiles.zip Scaffold Hunter saves the user profiles either on the hard disk or in a database. The corresponding database schema is contained in this zip file. This schema must be contained in the MySQL database before Scaffold Hunter can be run. This file is a dump from a MySQL 5.1 database and was generated with MySQL Administrator 1.2.5. It can be restored with the same program. III. InstallationGuide_Databases.pdf This document describes the installation of a local MySQL database server and the graphical user interface MySQL Administrator. Restoration of the profiles and sample databases are also described. IV. run_ScaffoldHunter.bat Windows batch file to run Scaffold Hunter with 1024 MByte of Memory. V. run_ScaffoldTreeGenerator.bat Windows batch file to run ScaffoldTreeGenerator with 1024 MByte of Memory. VI. ScaffoldHunter_readme.txt Textfile with advice for the installation of Scaffold Hunter. VII. ScaffoldTreeGenerator_readme.txt Textfile with advice for the installation of ScaffoldTree Generator

Drug Repurposing: Far Beyond New Targets for Old Drugs

Repurposing drugs requires finding novel therapeutic indications compared to the ones for which they were already approved. This is an increasingly utilized strategy for finding novel medicines, one that capitalizes on previous investments while derisking clinical activities. This approach is of interest primarily because we continue to face significant gaps in the drug–target interactions matrix and to accumulate safety and efficacy data during clinical studies. Collecting and making publicly available as much data as possible on the target profile of drugs offer opportunities for drug repurposing, but may limit the commercial applications by patent applications. Certain clinical applications may be more feasible for repurposing than others because of marked differences in side effect tolerance. Other factors that ought to be considered when assessing drug repurposing opportunities include relevance to the disease in question and the intellectual property landscape. These activities go far beyond the identification of new targets for old drugs

Physiochemical property space distribution among human metabolites, drugs and toxins

<p>Abstract</p> <p>Background</p> <p>The current approach to screen for drug-like molecules is to sieve for molecules with biochemical properties suitable for desirable pharmacokinetics and reduced toxicity, using predominantly biophysical properties of chemical compounds, based on empirical rules such as Lipinski's "rule of five" (Ro5). For over a decade, Ro5 has been applied to combinatorial compounds, drugs and ligands, in the search for suitable lead compounds. Unfortunately, till date, a clear distinction between drugs and non-drugs has not been achieved. The current trend is to seek out drugs which show metabolite-likeness. In identifying similar physicochemical characteristics, compounds have usually been clustered based on some characteristic, to reduce the search space presented by large molecular datasets. This paper examines the similarity of current drug molecules with human metabolites and toxins, using a range of computed molecular descriptors as well as the effect of comparison to clustered data compared to searches against complete datasets.</p> <p>Results</p> <p>We have carried out statistical and substructure functional group analyses of three datasets, namely human metabolites, drugs and toxin molecules. The distributions of various molecular descriptors were investigated. Our analyses show that, although the three groups are distinct, present-day drugs are closer to toxin molecules than to metabolites. Furthermore, these distributions are quite similar for both clustered data as well as complete or unclustered datasets.</p> <p>Conclusion</p> <p>The property space occupied by metabolites is dissimilar to that of drugs or toxin molecules, with current drugs showing greater similarity to toxins than to metabolites. Additionally, empirical rules like Ro5 can be refined to identify drugs or drug-like molecules that are clearly distinct from toxic compounds and more metabolite-like. The inclusion of human metabolites in this study provides a deeper insight into metabolite/drug/toxin-like properties and will also prove to be valuable in the prediction or optimization of small molecules as ligands for therapeutic applications.</p

Oligometastatic Prostate Cancer:Results of a Dutch Multidisciplinary Consensus Meeting

Background: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. Objective: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. Design, setting, and participants: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. Outcome measurements and statistical analysis: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. Results and limitations: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. Conclusions: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. Patient summary: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation. A multidisciplinary panel reached consensus that oligometastatic prostate cancer (OMPC) is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should provide insight into the biology and clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC

The current management of abdominal wounds – our experience

Catedra de chirurgie nr.1 „Nicolae Anestiadi”, Laboratorul de chirurgie Hepato-Pancreato-Biliară, USMF „Nicolae Testemițanu”, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Laparotomia exploratorie obligatorie a tuturor plăgilor penetrante ale abdomenului este un vestigiu al celor două războaie mondiale. Aplicarea acestei abordări a determinat incidență mare de laparotomii albe și morbiditate iatrogenă. Din aceste considerente în prezent se pledează pentru abordare diferențiată numită și management conservator selectiv. Scopul. Expunerea viziunii noastre a abordării diferențiate pentru pacienții cu plăgi abdominale. Material și metode. Lot de studiu – 126 pacienți spitalizați în IMU pe durata anilor 2013-2015 cu plăgi traumatice ale abdomenului. Pentru pacienții simptomatici la momentul adresării (instabili hemodinamici, iritare peritoneală, eviscerație) laparotomia exploratorie a fost mandatorie. Pentru cei asimptomatici la confirmarea caracterului penetrant al traumatismului a fost aplicată conduita nonoperatorie. Au fost analizate: structura traumatismului, incidența plăgilor penetrante, triggerul pentru laparotomie, rata intervențiilor terapeutice, rata laparotomiilor întârziate. Rezultate. 91(72,2%) pacienți au avut plăgi confirmate penetrante. 65 (71,4%) traumatizați au urmat laparotomie exploratorie fiind simptomatici, în 60(92,3%) cazuri au fost intervenții terapeutice, în 5(7,7%) – laparotomii albe. Au fost selectați pentru conduită nonoperatorie – 26(28,6%) pacienți cu plăgi penetrante, 10(38,4%) – penetrarea fiind confirmat prin laparoscopie diagnostică. S-a înregistrat în 3(11,5%) cazuri eșec a conduitei nonoperatorii, semne clinice de leziune a organelor interne fiind depistate până la 36h, laparotomia confirmându-le. Perioada postoperatorie a decurs fără complicații. Concluzii. Managementul nonoperator selectiv pentru plăgile penetrante ale abdomenului reprezintă o abordare tactică actuală, mai profesionistă şi argumentată, comparativ cu abordarea operatorie obligatorie. Aplicarea corectă a acestui algoritm minimalizează rata intervențiilor nonterapeutice şi morbidităţilor legate de aceasta. Eșecul conduitei nu determină riscuri suplimentare.Introduction. Mandatory laparotomy in all patients with penetrating abdominal is considered to be a vestige of the both world wars. This approach can result in an unacceptably high rate of nontherapeutic surgery and iatrogenic morbidity. For these reasons, nowadays, the selective non-operative management is preferred. Purpose. Showing our view on differentiated approach in patients with abdominal wounds. Material and methods. A study group of 126 patients with abdominal wounds, hospitalized in IEM between 2013-2015. The symptomatic patients with hemodynamic instability, peritonitis and evisceration underwent mandatory laparotomy. Stable patients without peritonitis, after confirming the penetrating feature of the wound, were managed without operation. The analyzed criteria were: trauma pattern, the incidence of penetrating wounds, the reason for laparotomy, therapeutic interventions rate, delayed laparotomies rate. Results. 91(72,2%) patients had confirmed penetrating wounds. 65(71,4%) patients were symptomatic and underwent exploratory laparotomy, 60(92,3%) of which were therapeutic and 5(7,7%) – non-therapeutic. The other 26(28,6%) patients were selected for non-operative treatment, 10(38,4%) of which underwent diagnostic laparoscopy. In 3(11,5%) cases there was a failure of non-operative management, the clinical signs of injured internal organs appeared after12-36h after injury and this patients underwent laparotomy. The postoperative period was favorable. Conclusion. The selective nonoperative management of penetrating abdominal wounds is considered an up-to date approach, more professional and argued, versus the mandatory operative approach. The correct application of this algorithm minimizes the rate of nontherapeutic interventions and related morbidities. Failure does not cause additional risk

Projects as Knowledge Swirls in the Technological Innovation: Romania's Situation

The present paper uses as research basis a new way of thinking regarding the relation between innovation and knowledge - the Knowledge Flow Percolation Model (KFPM). In this model’s center, human beings are seen as thinking electrons, both consuming and generating knowledge flows. Through the interdependent actions of individuals, knowledge circulates inside organizations, allowing them to innovate in order to obtain competitive advantages. But there is a wide range of barriers which impede the creation and movement of flows in the model grid and consequently, hinder their change into innovation. The solution proposed by this paper as one of the most adequate instruments to make KFPM more spreadable is the project. On this basis, in an empirical study, we try to demonstrate the hypothesis of the positive influence of projects, as knowledge swirls, on the development of innovative skills which will help solving problems in the organization, creating and widening of knowledge and reducing the barriers in knowledge transfer.This work was supported by the project “Post-Doctoral Studies in Economics: training program for elite researchers – SPODE” co-funded from the European Social Fund through the Development of Human Resources Operational Programme 2007-2013, contract no. POSDRU/89/1.5/S/61755

Synthesis and characterization of ZnO nanopowder by non-basic

Nanocrystalline ZnO particles were prepared from methanolic solutions of zinc acetate dihydrate without using base such as NaOH or LiOH through a colloid process carried out at a low temperature of 60 o C. The precipitate obtained after 12-72h contained ZnO, covered with polymeric species of zinc hydroxo acetate. The reaction course was studied by mass spectrometry means. To complete the hydrolysis process, up to pure ZnO, it was necessarily to reflux the white precipitate separate from methanolic solution, in water at 80 o C. We found that reaction time in the presence of methanol primarily influenced the size of the particles, while the reaction time in the presence of water mainly influenced the ZnO purity

Quantitative implications of the updated EARL 2019 PET-CT performance standards

Purpose Recently, updated EARL specifications (EARL2) have been developed and announced. This study aims at investigating the impact of the EARL2 specifications on the quantitative reads of clinical PET-CT studies and testing a method to enable the use of the EARL2 standards whilst still generating quantitative reads compliant with current EARL standards (EARL1). Methods Thirteen non-small cell lung cancer (NSCLC) and seventeen lymphoma PET-CT studies were used to derive four image datasets-the first dataset complying with EARL1 specifications and the second reconstructed using parameters as described in EARL2. For the third (EARL2F6) and fourth (EARL2F7) dataset in EARL2, respectively, 6 mm and 7 mm Gaussian post-filtering was applied. We compared the results of quantitative metrics (MATV, SUVmax, SUVpeak, SUVmean, TLG, and tumor-to-liver and tumor-to-blood pool ratios) obtained with these 4 datasets in 55 suspected malignant lesions using three commonly used segmentation/volume of interest (VOI) methods (MAX41, A50P, SUV4). Results We found that with EARL2 MAX41 VOI method, MATV decreases by 22%, TLG remains unchanged and SUV values increase by 23-30% depending on the specific metric used. The EARL2F7 dataset produced quantitative metrics best aligning with EARL1, with no significant differences between most of the datasets (p>0.05). Different VOI methods performed similarly with regard to SUV metrics but differences in MATV as well as TLG were observed. No significant difference between NSCLC and lymphoma cancer types was observed. Conclusions Application of EARL2 standards can result in higher SUVs, reduced MATV and slightly changed TLG values relative to EARL1. Applying a Gaussian filter to PET images reconstructed using EARL2 parameters successfully yielded EARL1 compliant data