Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay.

Eight nitropolycyclic aromatic hydrocarbons (PAHs), including 1- and 4-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene, 7-nitrobenz[a]anthracene, 6-nitrochrysene and 6-nitrobenzo-[a]pyrene and their parent PAHs were tested fro tumorigenicity in the newborn mouse model by i.p. administration at 1, 8, and 15 days after birth. Both pyrene and 1-nitropyrene induced similar incidences of hepatic tumors in males, yielding a 12-15% and a 21-28% tumor incidence at total doses of 700 and 2800 nmol per mouse, respectively. Liver tumors did not occur in females and the 3-10% lung tumor yield in both sexes was similar to that found in solvent-treated controls. The presumed proximate carcinogen, 1-nitrosopyrene, administered at 700 nmol per mouse, caused liver tumors in 45% of the males and in 9% of the females. 4-Nitropyrene was more tumorigenic than pyrene or 1-nitropyrene; at a dose of 2800 nmol, it induced liver tumors in 83% of the males and 7% of the females, with a lung tumor yield of 38 and 31%, respectively. Female mice treated with 200 nmol of 1,3-, 1,6- or 1,8-dinitropyrene did not develop liver tumors but the hepatic tumor incidence in males was 20, 32 and 16%, respectively, which was significantly greater than that found in mice treated with pyrene. In male mice administered 2800 nmol of benz[a]anthracene, the hepatic tumor incidence was 79%, while treatment with 7-nitrobenz[a]anthracene showed an incidence of only 28%. Similarly, 560 nmol of benzo[a]pyrene caused a 49% liver tumor yield in males while those given 6-nitrobenzo[a]pyrene had a 28% incidence. Treatment with benzo[a]pyrene also induced a 35 and 48% lung tumor incidence in males and females while the comparable values in 6-nitrobenzo[a]pyrene-treated mice were 14 and 2%. Chrysene administered at 2800 nmol per mouse induced hepatic and lung tumors in 41% and 21% of the males, respectively; at the 700-nmol dose, it induced only liver tumors in 29% of the males and in none of the females. In contrast, treatment with 6-nitrochrysene at 700 nmol per mouse resulted in a 76 and 23% hepatic tumor incidence in males and females, respectively. (ABSTRACT TRUNCATED AT 400 WORDS)
D-alanylation of Teichoic Acids in Bacilli impedes the immune sensing of peptidoglycan in Drosophila

Modification of cell wall components is a prominent mean for pathogens to hinder host immune defenses. Here, using the Drosophila model, we aimed at characterizing the role of D-alanine esterification of teichoic acids (TAs) in the resistance of Bacillus thuringiensis to host defenses in vivo. We show that, by preventing cationic antimicrobial effectors-mediated bacterial lysis, this cell wall modification also limits the release of peptidoglycan immunostimulatory fragments thus impeding their sensing and the subsequent induction of the IMD- NF-κB pathway. Interestingly, we show that this strategy is also adopted by Lactobacillus plantarum, a bona fide commensal, to fine-tune its immunomodulatory potential in the Drosophila gut. Markedly, we show that the D-alanylation of TAs is essential for the resistance of L. plantarum to gut lysozyme. Altogether our data shed light on the mechanism underlying the persistence and the low immunostimulatory potential of L. plantarum in the Drosophila gut.
Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941

The phosphatidylinositide 3-kinase pathway is frequently deregulated in human cancers and inhibitors offer considerable therapeutic potential. We previously described the promising tricyclic pyridofuropyrimidine lead and chemical tool compound PI-103. We now report the properties of the pharmaceutically optimized bicyclic thienopyrimidine derivatives PI-540 and PI-620 and the resulting clinical development candidate GDC-0941. All four compounds inhibited phosphatidylinositide 3-kinase p110α with IC50 ≤ 10 nmol/L. Despite some differences in isoform selectivity, these agents exhibited similar in vitro antiproliferative properties to PI-103 in a panel of human cancer cell lines, with submicromolar potency in PTEN-negative U87MG human glioblastoma cells and comparable phosphatidylinositide 3-kinase pathway modulation. PI-540 and PI-620 exhibited improvements in solubility and metabolism with high tissue distribution in mice. Both compounds gave improved antitumor efficacy over PI-103, following i.p. dosing in U87MG glioblastoma tumor xenografts in athymic mice, with treated/control values of 34% (66% inhibition) and 27% (73% inhibition) for PI-540 (50 mg/kg b.i.d.) and PI-620 (25 mg/kg b.i.d.), respectively. GDC-0941 showed comparable in vitro antitumor activity to PI-103, PI-540, and PI-620 and exhibited 78% oral bioavailability in mice, with tumor exposure above 50% antiproliferative concentrations for >8 hours following 150 mg/kg p.o. and sustained phosphatidylinositide 3-kinase pathway inhibition. These properties led to excellent dose-dependent oral antitumor activity, with daily p.o. dosing at 150 mg/kg achieving 98% and 80% growth inhibition of U87MG glioblastoma and IGROV-1 ovarian cancer xenografts, respectively. Together, these data support the development of GDC-0941 as a potent, orally bioavailable inhibitor of phosphatidylinositide 3-kinase. GDC-0941 has recently entered phase I clinical trials. [Mol Cancer Ther 2009;8(7):1725–38] [Mol Cancer Ther 2009;8(7):1725–38]
On the resistance and speed loss of full type ships in a seaway

ABSTRACT This paper presents results of a systematic study on the resistance and speed loss of full type ships in waves. The percentage resistance-increase in waves against experimentally measured calm water resistance data was estimated by use of two alternative empirical formulas, namely one proposed by the authors and the other one as recommended by ITTC. The obtained results clearly show that the percentage resistance-increase and the associated (involuntary) speed loss are strongly dependent on ship’s absolute size, loading condition and the operating seaway conditions and they can be satisfactorily quantified. This should be taken into account in the ship design process, when determining the sea margin for the selection of the machinery and propulsion system, when analysing sea trials and/or when preparing scaled model experiments to assess ship’s performance in realistic seaway scenarios.
Factors influencing outcomes and their measurement after brain injury

Acquired brain injury (ABI) is a major cause of morbidity and mortality, especially among younger people and the psychological sequelae can have chronic detrimental effects on patients’ life and wellbeing. It is important to have clinically relevant, validated measures to be able to determine a person’s psychological needs to structure interventions to improve outcomes. Measures designed for an ABI population have been developed but due to their rigid, closed question-based nature lived experience may not be captured. This means that an important source of clinically relevant information may be missed. The available evidence on the effect of coping, efforts and strategies to reduce stress, on various outcome measures used in the brain injury population was collated and findings were synthesised. Results suggest that not one coping or quality of life measure is used consistently and that the majority of these measures are not specific to this population. In addition, the studies show that excessive use of coping strategies, or the use of emotionally focused strategies, may have a detrimental effect on quality of life. The research paper addressed whether outcome measures miss clinically relevant information through their rigid structure. A mixed-methods analysis was used to compare information gathered from participants using an outcome measure (EBIQ) and that gained through analysis of semi-structured interviews. Ultimately, both methods have clinical value but the results from the outcome measure can be enriched through the use of qualitative information collected during interview. These two papers show that, while outcome measures are valuable in assessing a person’s needs and monitoring progress, there is a need for the more consistent use of outcome measures specific to the ABI population, in parallel with interviews to uncover issues which may otherwise be missed. A reflexive commentary on my journey through the research and thesis process is also presented.
Analisis Penyebab Ketidaktepatan Waktu Pelaporan Insiden Keselamatan Pasiendi RSU Bunda Thamrin

Pendahuluan Keselamatan pasien rumah sakit adalah suatu sistem dimana rumah sakit membuat asuhan pasien lebih aman yang meliputi asesmen risiko, identifikasi dan pengelolaanhal yang berhubungan dengan risiko pasien, pelaporan dan analisis insiden Tujuan Penelitian ini bertujuan untuk menganalisis penyebab ketidak tepatan waktu pelaporan insiden keselamatan pasien di RSU Bunda Thamrin Metode Desain penelitian ini adalah penelitian kualitatif dengan menggunakan pendekatan study fenomenology. Informan dalam penelitian ini adalah, Direktur, perawat, ketua KPRS dan champion tim KPRS Hasil penelitian menunjukkan bahwa ketidak tepatan waktu pelaporan insiden keselamatan pasien di RSU Bunda Thamrin disebabkan oleh rasa malas dan takut sehingga enggan untuk menuliskan kronologis insiden karena budaya keselamatan pasien yang belum menyeluruh di lingkungan rumah sakit Kesimpulan penelitian ini menyatakan bahwa ketidaktepatan waktu pelaporan insiden keselamatan pasien (IKP) disebabkan oleh gagalnya sosialisasi dan edukasi yang dilakukan oleh tim KPRS kepada seluruh karyawan rumah sakit.
Upregulated neurohumoral factors are associated with left ventricular remodeling and poor prognosis in rats with monocrotaline-induced pulmonary arterial hypertension.

BACKGROUND Left ventricular remodeling might be involved in the pathophysiology of right ventricular hypertrophy/failure due to pulmonary arterial hypertension (PAH), while the left ventricle is considered not under pressure/volume overload. METHODS AND RESULTS Rats with monocrotaline-induced PAH were used in the present study to examine whether upregulated neurohumoral factors may induce left ventricular (LV) remodeling and(/or) contribute to prognosis. Morphological analysis revealed a significant increase in the weight of the free walls of both ventricles and the interventricular septum, indicating biventricular hypertrophy, although systemic blood pressure was not elevated. RNase protection assay demonstrated the activation of a fetal gene program in the cardiac muscle of the left and right ventricular free walls. Similar activation of the fetal gene program was observed in the LV of rats continuously infused with angiotensin (AT) II, although this was not the case for rats infused with isoproterenol. Measured plasma levels of ATII, noradrenaline, and brain natriuretic peptide (BNP) were all significantly elevated in the PAH rats. Furthermore, the plasma BNP level positively correlated with the ratio of heart weight to body weight and the plasma level of ATII. Not right but LV hypertrophy was significantly reduced by treatment with an AT II type 1 receptor blocker, valsartan, whereas the effect of an adrenergic alpha1 and beta1,2 blocker, carvedilol, was borderline. Survival rate in the PAH rats was significantly improved when they were treated with valsartan or carvedilol. CONCLUSIONS Upregulated neurohumoral factors seem to play an important role in LV remodeling without mechanical overload, and are associated with impairment of prognosis in rats with PAH.
Enhanced adenoviral‐vector mediated gene transfer using human albumin solder

Laser tissue welding with human albumin solder (HAS) has been used as an alternative method of wound closure. Adenoviral vectors have been used to introduce various cytokine genes into wounds to accelerate wound closure. In the present study, we were interested in the effect of HAS on adenoviral vector transfer of the β‐galactosidase (β‐gal) gene in vitro and in vivo.
Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths.

IMPORTANCE Second-generation antipsychotics (SGAs) have increasingly been prescribed to Medicaid-enrolled children, either singly or in a medication combination. Although metabolic adverse effects have been linked to SGA use in youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has been challenging. OBJECTIVE To determine whether SGA initiation was associated with an increased risk for incident type 2 diabetes mellitus. Secondary analyses examined the risk associated with multiple-drug regimens, including stimulants and antidepressants, as well as individual SGAs. DESIGN, SETTING, AND PARTICIPANTS Retrospective national cohort study of Medicaid-enrolled youths between January 2003 and December 2007. In this observational study using national Medicaid Analytic eXtract data files, initiators and noninitiators of SGAs were identified in each month. Included in this study were US youths aged 10 to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for-service arrangement during the study. Those with chronic steroid exposure, a diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were ineligible. The mean follow-up time for all participants was 17.2 months. Youths were followed up until diagnosis of diabetes mellitus or end of follow-up owing to censoring caused by the transition into a Medicaid managed care arrangement or Medicaid ineligibility (the end of available data). Propensity weights were developed to balance observed demographic and clinical characteristics between exposure groups. Discrete failure time models were fitted using weighted logistic regression to estimate the risk for incident diabetes mellitus between initiators and noninitiators. EXPOSURE A filled SGA prescription. MAIN OUTCOMES AND MEASURES Incident type 2 diabetes mellitus identified through visit and pharmacy claims during the observation period. RESULTS Among 107,551 SGA initiators and 1,221,434 noninitiators, the risk for incident diabetes mellitus was increased among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared with youths initiating only SGAs, the risk was higher among SGA initiators who used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95% CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators who were concomitantly using stimulants. As compared with a reference group of risperidone initiators, the risk was higher among those initiating ziprasidone (OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21-2.07; P = .001) but not quetiapine fumarate or olanzapine. CONCLUSIONS AND RELEVANCE The risk for incident type 2 diabetes mellitus was increased among youths initiating SGAs and was highest in those concomitantly using antidepressants. Compared with risperidone, newer antipsychotics were not associated with decreased risk.
Research with Homeless People Uncovers a Model of Health

This grounded theory research study explored health experiences of 11 homeless persons in shelters in three New Brunswick cities and the strategies that they used to attain, maintain, or regain health. Audiotaped interviews were conducted, transcribed verbatim, and analyzed. The model that emerged from analysis consists of three pathways to health. This model of health has two central components, person and health. Person is influenced directly by family values and beliefs, and directly and indirectly by societal values and beliefs. Health is the outcome and is reached through two mediating factors of lifestyle behaviors and sector services. The first pathway to health contains the mediating factor of lifestyle behaviors, the second contains the mediating factor of sector services, and the third contains both mediating factors. Pathway strategies of choosing, accessing, and appraising appropriateness of methods influence the active participation of the person that directs the action within the model. Implications of the study include that a fragmented system of help hinders access to services intended to promote health in this population.
An open IoT framework based on microservices architecture

With the continuous development and evolvement of Internet of Things (IoT), monolithic application becomes much larger in scale and even more complex in structure. This leads to poor scalability, extensibility and maintainability. In response to those challenges, microservice architecture has been introduced in the field of IoT application, due to its flexibility, lightweight and loose coupling. However, the existing IoT framework of microservice mainly focus on a specific domain, therefore, this greatly limits its application. In this paper, we propose a general microservice system framework for the IoT application, which is a better scalable, extendable and maintainable architecture. We introduce its system design and related microservices, and emphasize on core service and device communication from service layer to physical layer. It has better capacity to support interoperability and accommodate heterogeneous objects. In addition, this framework can easily achieve more application integration such as automation, intelligence, Geo service and Big Data.
Functioning of the Intestinal Ecosystem: From New Technologies in Microbial Research to Practical Poultry Feeding – A Review

Abstract Unlike classical microbiology which focuses on bacteria capable of growing in vitro, metagenomics is a study of genetic information originating from microflora which aims to characterise the microbiome, namely the common genome of bacteria, archaea, fungi, protozoa and viruses living in the host. Metagenomics relies on next-generation sequencing (NGS), a large-scale sequencing technique which allows millions of sequential reactions to be carried out in parallel to decode entire communities of microorganisms. Metagenomic analyses support taxonomic analyses (involving gene fragments encoding ribosomal RNAs 5S and 16S in bacteria) or functional analyses for identifying genes encoding proteins that participate in the regulation of metabolic pathways in the body. New metagenomics technologies expand our knowledge of the phylogenetic structure of microflora in the gastrointestinal tract of poultry, and they support the identification of previously unknown groups of microbiota, mainly those occurring in small numbers. Next-generation sequencing also provides indirect information about the quantitative structure of the genes of gut microorganisms, but microbial activity and changes in the proportions of microbial metabolites that affect the host’s intestinal integrity and metabolism remain insufficiently investigated. Therefore, research studies are undertaken to investigate the proportions of the key microbial metabolites in the intestinal contents of poultry relative to changes in the population size of the most important bacterial groups, including those determined by cheaper techniques.
Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10–15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×109/L) or partial (platelet count between 50 and 150×109/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients.
Fostering wind in foreign waters: Governmental roles stimulating export of the Dutch offshore wind sector

In a rapidly expanding offshore wind market, governments are evaluating their role in the support of the export of their domestic companies. This thesis looks at what roles governments utilize in the export domain of offshore wind. Four governmental roles are identified and their prevalence is rated in different stages of a novel representation of the export process. A framework of these roles and export stages is applied to the Dutch, Danish and German offshore wind sector by performing a comparative case study. The case studies are conducted using a combination of desk study and 26 expert interviews. The study finds a range of recommendations for the Dutch government to improve its promotion of exports in the Dutch sector. Additionally, the study finds a range of patterns of prevalences of governmental roles which are discussed. The instruments and roles utilized in the earlier stages of the export process are theorized to be more technology-related, the instruments and roles later in the export process are more generalizable for all export processes.
Identiﬁcation and Characterization of Noncoding Small RNAs in Streptococcus pneumoniae Serotype 2 Strain D39 (cid:1)

We report a search for small RNAs (sRNAs) in the low-GC, Gram-positive human pathogen Streptococcus pneumoniae . Based on bioinformatic analyses by Livny et al. (J. Livny, A. Brencic, S. Lory, and M. K. Waldor, Nucleic Acids Res. 34:3484–3493, 2006), we tested 40 candidates by Northern blotting and conﬁrmed the expression of nine new and one previously reported (CcnA) sRNAs in strain D39. CcnA is one of ﬁve redundant sRNAs reported by Halfmann et al. (A. Halfmann, M. Kovacs, R. Hakenbeck, and R. Bruckner, Mol. Microbiol. 66:110–126, 2007) that are positively controlled by the CiaR response regulator. We characterized 3 of these 14 sRNAs: Spd-sr17 (144 nucleotides [nt]; decreased in stationary phase), Spd-sr37 (80 nt; strongly expressed in all growth phases), and CcnA (93 nt; induced by competence stimulatory peptide). Spd-sr17 and CcnA likely fold into structures containing single-stranded regions between hairpin structures, whereas Spd-sr37 forms a base-paired structure. Primer extension mapping and ectopic expression in deletion/insertion mutants conﬁrmed the independent expression of the three sRNAs. Microarray analyses indicated that insertion/deletion mutants in spd-sr37 and ccnA exerted strong cis -acting effects on the transcription of adjacent genes, indicating that these sRNA regions are also cotranscribed in operons. Deletion or overexpression of the three sRNAs did not cause changes in growth, certain stress responses, global transcription, or virulence. Constitutive ectopic expression of CcnA reversed some phenotypes of D39 (cid:1) ciaR mutants, but attempts to link CcnA to -E to comC as a target were inconclusive in ciaR (cid:2) strains. These results show that S. pneumoniae , which lacks known RNA chaperones, expresses numerous sRNAs, but three of these sRNAs do not strongly affect common phenotypes or transcription patterns.