The NORMAN Suspect List Exchange (NORMAN‑SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https:// www. norman-​netwo rk. com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https:// www. norman-​netwo rk. com/ nds/ SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo. org/ commu nities/ norman-​sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https:// pubch em. ncbi. nlm. nih. gov/) and the US EPA’s CompTox Chemicals Dashboard (https:// compt ox. epa. gov/ dashb oard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https:// pubch em. ncbi. nlm. nih. gov/ class ifica tion/# hid= 101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https:// www. norman-​netwo rk. com/ nds/ SLE/).NORMAN AssociationLuxembourg National Research Fund A18/BM/12341006European Union's Horizon 2020 research and innovation programme 101036756National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health (NIH)National Health and Medical Research Council (NHMRC) of Australia EL1 2009209Australian Research Council DP190102476 Queensland Department of HealthInstituto de Salud Carlos III European Commission CP19/00060 European Union through Fondo Europeo de Desarrollo Regional (FEDER)Federal Ministry of Education & Research (BMBF) FKz: 02WRS1495 A/B/EFWO 11G1821NNIH via grant NIH NIGMS R01GM092218 NIH via grant NIH NCI 1R03CA222452-01Vanderbilt Chemical Biology Interface training program 5T32GM065086-16Netherlands Organization for Scientific Research (NWO) 15747SOLUTIONS project (European Union's Seventh Framework Programme for research, technological development and demonstration) 603437HBM4EU (European Union's Horizon 2020 research and innovation programme 733032German Research Foundation (DFG) 441958208NaToxAq (European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant 722493German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) (FKZ) 3716 67 416 0German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) Project (FKZ) 3719 65 408 0EU Cohesion Funds within the project Monitoring and assessment of water body status 310011A366Swiss Federal Office for the Environment (FOEN)Canadian Institutes of Health Research (CIHR) Genome CanadaMAVA foundationValery FoundationNational Science Foundation (NSF) RUI-1306074 National Natural Science Foundation of China (NSFC) 22193051 21906177China Postdoctoral Science Foundation 2019M650863Environmental Protection Administration, Executive Yuan, R.O.C. Taiwan (Taiwan EPA) 108C002871Swiss Federal Office for the EnvironmentUnited States Environmental Protection AgencyCenter for Forestry Research & Experimentation (CIEF)European Commission 2019/040Marie Sklodowska-Curie grant 859891 European Commission European Commission Joint Research Centre 308610 289511Joint Programming Initiative FOODBALL 2014-17 MCIN/AEI RYC2020-028901-IESF investing in your futureAugust T Larsson Guest Researcher Programme from the Swedish University of Agricultural SciencesGerman Federal Ministry of Education and Research within the RiSKWa program 02WRS1273 02WRS1354RECETOX research infrastructure (the Czech Ministry of Education, Youth and Sports) LM2018121CETOCOEN PLUS project CZ.02.1.01/0.0/0.0/15_ 003/0000469 CETOCOEN EXCELLENCE Teaming 2 project - Czech ministry of Education, Youth and Sports CZ.02.1.01/0.0/0.0/1 7_043/000963

Insecticide resistance in malaria vectors in central Sudan

Malaria is the leading cause of mortality and morbidity in Sudan. The annual malaria cases and deaths are estimated at 7.5 million and 35, 000 respectively. One of the possible factors that have led to this situation is the development of insecticide resistance in the main malaria vector in Sudan, Anopheles arabiensis. This study therefore, was initiated to identify the malaria vectors in Gezira and Sennar states of central Sudan, determine their susceptibility levels to the different classes of insecticides used for malaria vector control, identify mechanisms of resistance, and determine the sporozoite infection rate and the blood meal sources in these populations. The polymerase chain reaction (PCR) for species identification revealed that An. arabiensis was the only member of the An. gambiae complex present in the study area. The blood meal analysis using ELISA showed high anthropophily with 89.2% feeding on humans. The overall sporozoite infection rate was 2.3 %. WHO susceptibility tests showed complete susceptibility of An. arabiensis to bendiocarb (100% mortality) and multiple resistance to permethrin (54-78%), DDT (55-66%) and malathion (76-78%). The kdr mutation analysis revealed the presence of the West African kdr allele with the majority of specimens being heterozygous (RS). The kdr in DDT/permethrin susceptible specimens were: 15% homozygous for the kdr mutation (RR), 64.2% heterozygous (RS) and 20.8% homozygous for the susceptible allele (SS). Amongst the DDT/permethrin resistant specimens, 13% were SS, 48.7% RS and 38.3% RR. The apparent lack of correlation between kdr and resistant phenotype strongly suggests that other resistance mechanisms are playing a role

Development a New Intelligent Mobile Robot to Avoid Obstacle

The project is a robot that automatically by passes barriers to reach a specific goal with an ultrasonic help that senses obstacles and measures the remaining transitions before the collision is meet. The robot changes its course with a couple of DC motors, Robot runs automatically without any interference by the Proportional-Integral-Derivative (PID) algorithm. The goal of this paper is to develop a path planning method that is capable of planning the mobile robot path from the starting position to the target position in different environments. However, the parameters of membership functions and PID controller parameters have optimized by using particle swarm optimization (PSO) algorithm. In addition to that, the proposed method with two Schemes of motion controllers are test with varying static and dynamic environments with and without load. The artificial potential field algorithm is introduce for path planning of mobile robot. However, the potential field algorithm is effective in avoiding unknown obstacles, but it contains minimal local problems, then a modified field algorithm is introduce to overcome some of the local minimum problems in the environment. Therefore, it is enhancing the performance of potential field algorithm and to produce a more efficient path planning method, that to allow mobile robot to navigate in dynamic and complex environments. As well as, simulation of mobile robot is design to test and implement the proposed method and control schemes using MATLAB and the software is develops by using C++ language and Arduino IDE. DOI: 10.7176/CEIS/10-3-03 Publication date: April 30th 201

An assessment of the nutritional status of students in governmental primary schools in U.A.Q.

Aim: To provide a summary of the recent data on the nutritional status of school-aged children in developing countries and countries in transition and identify issues of public health concern. An assessment of the nutritional status of students in governmental primary schools in U.A.Q. Methods:  A retrospective study was conducted from 2016 to 2017 on the nutrition status of Grade 1 school children in Government primary schools. The data was collected from questionnaires that were distributed routinely. Results: A total of 317 students from 7 different primary public schools in UAQ, with an age range from 5-7 years.  Students with Chronic diseases, congenital anomalies, and hereditary diseases were excluded. The available data indicate that the nutritional status of the students in the reviewed schools is adequate. Where it has shown that mean body mass index (BMI) was 15.2. Underweight, Overweight obesity was not prominent with a percentage of 12% and 10 % respectively. As for anemia, only 7% were diagnosed biochemically. With the mean hemoglobin of 12.1 mg/dl overall.  Conclusions. The available data indicate that malnutrition is not a health issue in primary students in UAQ primary public schools. These findings emphasize the impact of the school health program on primary students

The Effect of Oral Contraceptive Pills on The Gene Mutation of Factor V Leiden among Sudanese Women

Oral contraceptive pills are problems for women, often have many effects, and may cause several diseases. The purpose of this research was to determine the impact of oral contraceptive pills on factor V sufferers. This case-control study conducted in Khartoum Sudan during the period from April to November 2018. The study included 50 women who used oral contraceptive as a case and 50 women who did not use oral contraceptive pills as a control, all of whom were verbally informed of the study and approved for participation. The PCR do for each sample. The results obtained from cases show that the mean age is 30±5.5 and divided into three groups less than 20 with a lower frequency of 4 % (2/50), (20-35) with a higher incidence of 80 % (40/50) and a higher rate of 16 % (8/50) for more than 35 years. Most cases use the oral contraceptive pill for more than one year at a frequency of 60% (30/50) with a mean of 2±0.8. The most frequent oral contraceptive pill use was levonorgestrel 88% (44/50), followed by desogestrel 12% (6/50). The study concludes that there is no significant difference in gene mutation between case and control. There was also an insignificant association between the mutation and demographic data

ANTIBACTERIAL EFFECT AND PHYTOCHEMICAL ANALYSIS OF THE SHOOT SYSTEM OF RUBUS CANESCENS DC. GROWING IN LEBANON

The misuse of antibiotics followed by improved fitness of resistant strains of infectious microorganisms hindered the efficacy of many known antimicrobial agents, and fueled research for the discovery of novel remedies. The current study aims at assessing the antimicrobial activity and understanding the mechanism of action of Rubus canescens DC. growing wild in Lebanon, as well as qualitatively determining its phytochemical profile. The antibacterial activity, MIC, and MBC of the extracts were evaluated by two-fold dilution. Time-kill curves were plotted to assess the bactericidal activity of the R. canescens DC. extracts against the growth of microorganisms, and TEM images were collected to confirm such effect. Overall, the extracts exhibited good antibacterial activity against MRSA and E. coli but not against S. pneumoniae and K. pneumoniae as determined by measuring the inhibition zones in plate-diffusion assays. TEM images of treated microorganisms revealed that the R. canescens DC. extracts induced irreversible deformations and damage to the cell membranes of the microorganisms leading to the leakage of cytoplasmic components and eventual cell death. Analysis of Time-Kill curves indicated that the extracts induced 100% killing of the test microorganisms within 10-18 h at the respective MBC. Finally, qualitative phytochemical analysis was conducted to decipher the active ingredients in the plant extracts.The current study reports the first data on the antimicrobial activity of different parts of R. canescens DC. Such promising data opens new avenues for broader assessment of the pharmacological profile of the scarcely investigated R. canescens DC

The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells

BACKGROUND: The control of breast cell survival is of critical importance for preventing breast cancer initiation and progression. The activity of many proteins which regulate cell survival is controlled by reversible phosphorylation, so that the relevant kinases and phosphatases play crucial roles in determining cell fate. Several protein kinases act as oncoproteins in breast cancer and changes in their activities contribute to the process of transformation. Through counteracting the activity of oncogenic kinases, the protein phosphatases are also likely to be important players in breast cancer development, but this class of molecules is relatively poorly understood. Here we have investigated the role of the serine/threonine protein phosphatase 4 in the control of cell survival of breast cancer cells. METHODS: The breast cancer cell lines, MCF7 and MDA-MB-231, were transfected with expression vectors encoding the catalytic subunit of protein phosphatase 4 (PP4c) or with PP4c siRNAs. Culture viability, apoptosis, cell migration and cell cycle were assessed. The involvement of phosphoprotein enriched in astrocytes 15kDa (PEA15) in PP4c action was investigated by immunoblotting approaches and by siRNA-mediated silencing of PEA15. RESULTS: In this study we showed that PP4c over-expression inhibited cell proliferation, enhanced spontaneous apoptosis and decreased the migratory and colony forming abilities of breast cancer cells. Moreover, PP4c down-regulation produced complementary effects. PP4c is demonstrated to regulate the phosphorylation of PEA15, and PEA15 itself regulates the apoptosis of breast cancer cells. The inhibitory effects of PP4c on breast cancer cell survival and growth were lost in PEA15 knockdown cells, confirming that PP4c action is mediated, at least in part, through the de-phosphorylation of apoptosis regulator PEA15. CONCLUSION: Our work shows that PP4 regulates breast cancer cell survival and identifies a novel PP4c-PEA15 signalling axis in the control of breast cancer cell survival. The dysfunction of this axis may be important in the development and progression of breast cancer

Theoretical Study of Solvent Effects on 1,3- Dipolar Cycloaddition Reaction

في هذه الدراسة تم اجراء التحليل الانحداري لثابت التفاعل 15 مع معاملات المذيبات لمجموعتين من تفاعلات الاضافة الحلقي ال1و3-ثنائي القطب. الاولى هي تفاعل الازوميثاين(1)  مع السايكلواوكتاين (2),و اليينامين(3), و ثنائي مثيل اسيتيلين كاربوكسيليت(4). والمجموعة الثانية هي تفاعل النيترونات 5و6 مع الدايبولاروفيل 7 . كما تم اجراء الحسابات الشبه تجريبية للمتفاعلات حيث رسمت القيم الكمية الناتجة ضد معاملات التفاعل وضد معاملات المذيبات. وتم الحصول على نتائج متباينة الجودة لهذه التفاعلات. واجري تحليل رج الانحداري لغرض تصحيح الشذوذ الخطي للنماذج ذات المعاملات المتعددة. الغرض من هذه الدراسة هو الحصول على نموذج او نماذج والتي بواسطتها يمكن التنبؤ بالظروف المثالية للتفاعل قبل العمل المختبري.In the present study the regression analysis of the rate constant k 15with solvent parameters, for two sets of 1,3-dipolarcycloaddition reactions were done. The first was the reaction azomethine 1 with cyclooctyne 2, ynamine 3 and dimethyl acetylenecarboxylate (4) in different nonprotic solvents. The second were the reactions of the nitrones 5 and 6 with dipolarophile 7. Semiempirical calculations (PM3) were done for the reactants. The resulting quantum descriptors HOMO-LUMO and the transition state quantum descriptors (LUMOdipolarophile - HOMOdipole (HdL) and LUMOdipole – HOMOdipolarophile (LdH)) were plotted against solvent parameters, in order to obtain predictive computational models. Good to excellent correlations were obtained for these reactions. The multiparameteric models obtained were corrected for collinearity   by using Ridge regression

Exact Solution of Bianchi Type-V Model with Variable Cosmological Term- and G

The homogeneous anisotropic Bianchi typeV cosmological model with variable gravitational and cosmological constants is investigated. Exact solutions of the Einstein eld equations are presented in terms of adjustable parameter of quantum eld in a curved and expanding background. We found that the Cosmological constant decreases as time increases whereas the gravitational constants increases respectively. The universe in this model approaches isotropy state at late period of time. A clear presention for the physical and kinematical quantities of the model are also presented. v

Interactions between PP4 and PEA-15 in the regulation of cell proliferation and apoptosis of breast cancer cells

Background The serine/threonine protein phosphatase 4 (PP4) is recognised to regulate a variety of cellular functions. Our previous work has shown that the catalytic subunit of PP4 (PP4c) promotes cell death and inhibits proliferation in breast cancer cells, suggestive of a role of PP4c as tumour suppressor gene. Phosphoprotein enriched in astrocytes 15 (PEA-15), a member of the death effector domain protein family known to control cell survival, is reported to be regulated by PP4c. The aims of this study were to investigate the involvement of PEA-15 in mediating the effects of PP4c on breast cancer cells. Method PEA-15 phosphorylation was examined by western blot analysis on proteins extracted from MCF7 and MDA-MB-231 cells over-expressing PP4 and PP4 knock down cells. To investigate the role of PEA-15 in mediating the effects of PP4c, MCF7 and MDA-MB-231 were transfected with control (-) siRNA or with three different PEA-15 specific siRNAs. 48 h post-transfection, control cells (transfected with negative control siRNA) and cells transfected with PEA-15 siRNAs were transiently transfected with pcDNA3.1-PP4c expression construct or pcDNA3.1. Cell viability and apoptosis level were assessed post transfection. Results In MCF7 and MDA-MB-231 cells, the phosphorylation state of PEA-15 increased when PP4c expression was suppressed and decreased when PP4c was over-expressed. Over-expression of PP4c in cells transfected with (-) siRNA caused 50% reduction in viability compared to cells transfected with empty vector. Cells transfected with PEA-15 siRNAs showed a decrease in viable cell number and long term survival. However, over-expression of PP4c in these cells did not have any additional effect on the decrease in cell viability. Conclusion These observations suggest that the induction of apoptosis by over-expression of PP4c is mediated, at least in part, by the dephosphorylation of PEA-15. The interactions between PEA-15 and PP4c may therefore be critical in breast cancer tumorigenesis