Piperazinylpyrimidine analogues as protein kinase inhibitors

The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same

Total L-carnitine and insulin resistance in non-obese and obese Iraqi women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine illnesses affecting reproductive - age women. L-carnitine has important roles in oxidative stress, energy production and glucose metabolism. It affects insulin resistance as decreased plasma carnitine level has been well reported in type II diabetes mellitus. Hence, it means L-carnitine may reduce insulin resistance which is found in PCO disease. Objective: This study aims to measure the level of L-carnitine and insulin resistance in both obese and non- obese patients with PCOS. Patients and Methods: Sixty women within the reproductive age with PCOS (30 obese and 30 non- obese) were recruited from the Gynecology and Obstetrics Outpatient Clinic in Baghdad Teaching Hospital from June 2016 to June 2017. The data collected for each case included: Height, weight, waist circumference, blood pressure, obstetrical, medical, and medication history as well as ultrasound results. A physical examination was done to evaluate the clinical signs of hyperandrogenism. Biochemical measurements included fasting blood sugar, leutinizing hormone, follicular stimulating hormone, Testosterone and lipid profile were measured together with total L-carnitine (using L-Carnitine Assay Kit Sigma-Aldrich Co.). Insulin resistance was diagnosed according to National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III). PCOS is diagnosed according to the Rotterdam criteria. Results: This study revealed that insulin resistance (IR) was present in 51.7% of PCOS patients, which was higher in obese PCOS patients (73.3%) than  in the non-obese (30%). Age of patients, serum cholesterol, LH, and FSH were not related to IR. High mean BMI, waist circumference, FBS and triglyceride were significantly associated with IR (p < 0.05), while low serum HDL and L-Carnitine were associated with IR (p < 0.05). The mean serum total L-carnitine in this study was 34.03μmol/L. Obese women had lower carnitine levels than non-obese women and low serum L-Carnitine was associated with IR. Serum triglyceride, FBS and testosterone were correlated negatively with serum L-carnitine (p < 0.05) and serum HDL correlated positively with serum L-carnitine (p value = 0.001). Conclusions: The mean value of serum total L-carnitine among the non-obese PCOS women was higher than among the obese ones. Low serum L-carnitine is associated with insulin resistanc

Haploinsufficiency of myostatin protects against aging‐related declines in muscle function and enhances the longevity of mice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/1/acel12339-sup-0003-TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/2/acel12339.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/3/acel12339-sup-0004-TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/4/acel12339-sup-0002-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112228/5/acel12339-sup-0001-DataS1.pd

Transcriptome profiling of immune responses to cardiomyopathy syndrome (CMS) in Atlantic salmon

<p>Abstract</p> <p>Background</p> <p>Cardiomyopathy syndrome (CMS) is a disease associated with severe myocarditis primarily in adult farmed Atlantic salmon (<it>Salmo salar </it>L.), caused by a double-stranded RNA virus named piscine myocarditis virus (PMCV) with structural similarities to the <it>Totiviridae </it>family. Here we present the first characterisation of host immune responses to CMS assessed by microarray transcriptome profiling.</p> <p>Results</p> <p>Unvaccinated farmed Atlantic salmon post-smolts were infected by intraperitoneal injection of PMCV and developed cardiac pathology consistent with CMS. From analysis of heart samples at several time points and different tissues at early and clinical stages by oligonucleotide microarrays (SIQ2.0 chip), six gene sets representing a broad range of immune responses were identified, showing significant temporal and spatial regulation. Histopathological examination of cardiac tissue showed myocardial lesions from 6 weeks post infection (wpi) that peaked at 8-9 wpi and was followed by a recovery. Viral RNA was detected in all organs from 4 wpi suggesting a broad tissue tropism. High correlation between viral load and cardiac histopathology score suggested that cytopathic effect of infection was a major determinant of the myocardial changes. Strong and systemic induction of antiviral and IFN-dependent genes from 2 wpi that levelled off during infection, was followed by a biphasic activation of pathways for B cells and MHC antigen presentation, both peaking at clinical pathology. This was preceded by a distinct cardiac activation of complement at 6 wpi, suggesting a complement-dependent activation of humoral Ab-responses. Peak of cardiac pathology and viral load coincided with cardiac-specific upregulation of T cell response genes and splenic induction of complement genes. Preceding the reduction in viral load and pathology, these responses were probably important for viral clearance and recovery.</p> <p>Conclusions</p> <p>By comparative analysis of gene expression, histology and viral load, the temporal and spatial regulation of immune responses were characterised and novel immune genes identified, ultimately leading to a more complete understanding of host-virus responses and pathology and protection in Atlantic salmon during CMS.</p

DISCOVERY OF MUTANT SELECTIVE PLATELET DERIVED GROWTH FACTOR RECEPTOR (PDGFR) FAMILY KINASE INHIBITORS

In the past decade there has been rapid growth in the number of FDA approved cancer drugs within the class known as kinase inhibitors. Some kinase inhibitors have become first line chemotherapy for certain tumor types. For example, imatinib (Gleevec) is used effectively to treat Ph+ chronic myelogenous leukemia. Unfortunately, resistance to kinase inhibitors can develop through upregulation of, or mutation of the target kinase resulting in decreased drug binding

Experimental behaviour of concrete-filled steel tube composite beams

The main objective of this study is to highlight the performance of beams composed of lightweight concrete-filled steel tubes (square and circle sections) composite with reinforced concrete deck slab. A total of nine composite beams were tested included two circular and seven square concrete-filled steel tubes. Among the nine composite beams, one beam, S20-0-2000, was prepared without a deck slab to act as a reference specimen. The chief parameters investigated were the length of the specimen, the compressive strength of the concrete slab, and the effect of the steel tube section type. All beams were tested using the three-point bending test with a concentrated central point load and simple supports. The test results showed that the first crack in the concrete deck slab was recorded at load levels ranging from 50.9% to 77.2% of the ultimate load for composite beams with square steel tubes. The ultimate load increased with increasing the compressive strength of the concrete slab. Shorter specimens were more stiffness than the other specimens but were less ductile. The slip values were equal to zero until the loads reached their final stages, while the specimen S20-55-1100 (short specimen) exhibited zero slip at all stages of the load. The ultimate load of the hollow steel tube composite beam was 13.2% lower than that of the reference beam. Moreover, the ductility and stiffness of the beam were also higher for beams with composite-filled steel tubes

Piperazinylpyrimidine analogues as protein kinase inhibitors

The invention provides novel compounds based on piperazinylpyrimidine derivatives to be used as protein kinase inhibitors. The compounds may be useful in treating or preventing different cellular proliferation disorders, such as cancer. The present invention also provides methods of preparing these compounds, and methods of using the same

Investigating the Collocational Competence of Polish and Yemeni Learners of English as a Foreign Language

One of the difficulties EFL learners frequently experience in English is the choice of words to achieve native-like competency. The present study investigates the collocational competence of Polish and Yemeni learners of English as a foreign language. The thesis opens with a review of the literature on collocations in English from a linguistic perspective, followed by a presentation of studies devoted to investigations of collocational competence in a cross-linguistic perspective. The purpose of the empirical study is to investigate the collocational competence in Polish and Yemeni advanced learners of English at the university level. Eighty subjects participated in the present study, 40 Polish and 40 Yemeni advanced learners of English. Two elicitation tasks were conducted: blank-filling and multiple-choice tests which consisted of 30 test items each, containing verb-noun collocations with verbs missing or to be selected. Results obtained from the elicitation tasks showed that, in spite of the fact that the participants are advanced learners of English, their level of collocational competence shows a variety of problems. The Polish participants did better than the Yemeni group with statistically significant differences between the two groups. Recognition knowledge of collocations was better than the recall one, but there were interesting irregularities in that regard in the two elicitation tasks. The Polish group’s mean scores on the recognition and the recall tests (17.88, 14.12, respectively) were significantly higher than the Yemeni means (13.13, 9.38). The native-target language congruency in the collocations seemed to affect the learners' collocational performance on the tests. The following nine types of errors were identified in the Polish and Yemeni results: interference errors (L1 transfer and literal translation) (24.9%), (29.2%); near synonyms (10.7%, 10.6%); avoidance (9.6%, 5.3%); idiomaticity (18.5%, 18.7%); overgeneralization (14.4%, 9.7%); approximation (2.5%, 2.7%); paraphrase (1.7%, 0.5%); usage of irrelevant collocations (4.3%, 7.2%); and the use of de-lexicalized verbs (13.4% and 16.1% respectively). Following these findings, some implications for improving second/foreign language learners' collocational knowledge are formulated to enhance their proficiency in the target language, such as raising their collocational awareness and explicit teaching and learning of collocations

DISCOVERY OF MUTANT SELECTIVE PLATELET DERIVED GROWTH FACTOR RECEPTOR (PDGFR) FAMILY KINASE INHIBITORS

In the past decade there has been rapid growth in the number of FDA approved cancer drugs within the class known as kinase inhibitors. Some kinase inhibitors have become first line chemotherapy for certain tumor types. For example, imatinib (Gleevec) is used effectively to treat Ph+ chronic myelogenous leukemia. Unfortunately, resistance to kinase inhibitors can develop through upregulation of, or mutation of the target kinase resulting in decreased drug binding