Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting 14-3-3 Sensitizes Native and Mutant BCR-ABL to Inhibition with U0126, Rapamycin and Bcl-2 Inhibitor GX15-070.

Recurring chromosomal abnormalities in human leukemias result in expression of a wide spectrum of constitutively activated fusion tyrosine kinases, including BCR-ABL associated with t(9;22)(q34;q22) chronic myelogenous leukemia (CML). Small molecule tyrosine kinase inhibitors, such as imatinib, are effective therapies for BCR-ABL-mediated human leukemias. However, clinical drug resistance occurs, which warrants development of alternative and/or complementary therapeutic strategies to target critical downstream signaling molecules. We recently demonstrated that disrupting 14-3-3/ligand association by a peptide-based 14-3-3 competitive antagonist, R18 induces significant apoptosis, partially through reactivation of AKT-inhibited pro-apoptotic FOXO3a in FGFR1 fusion transformed hematopoietic cells [Dong et al, Blood, 2007, 110(1):360–9]. Here we report that targeting 14-3-3 by R18 effectively induced significant apoptosis in Ba/F3 and K562 cells expressing BCR-ABL, through liberation and reactivation of FOXO3a, but not by affecting 14-3-3/BCR-ABL association or BCR-ABL kinase activity. In addition, co-immunoprecipitation experiments revealed that R18 was not able to disrupt 14-3-3/BAD association, suggesting a model that targeting 14-3-3 by R18 induces apoptosis in BCR-ABL transformed cells, at least in part, through liberation and reactivation of FOXO3a phosphorylated and inhibited by activated AKT, but not BAD inhibited by ERK. Thus, we hypothesize that targeting 14-3-3 by R18 may potentiate the inhibition of BCR-ABL transformed cells induced by blocking the parallel MEK1/ERK pathway, pro-survival Bcl-2 proteins, or other signaling effectors downstream of AKT. Indeed, R18 sensitized BCR-ABL transformed cells to inhibition with MEK1 inhibitor U0126, Bcl-2 inhibitor GX15-070, or mTOR inhibitor rapamycin, and the combined treatment of R18 with these anti-cancer reagents synergistically induced apoptotic cell death. Moreover, treatment of these reagents potentiates R18-induced reactivation of pro-apoptotic FOXO3a with enhanced expression of downstream transcription targets including p27 kip1 and Bim1, suggesting a potential molecular mechanism of the combined therapy. Furthermore, R18 induced apoptotic cell death in cells expressing diverse imatinib-resistant BCR-ABL mutants, including T315I. This inhibition was enhanced by treatment of R18 in combination with U0126 and rapamycin. Together, our findings suggest a novel therapeutic strategy that targeting 14-3-3 may potentiate the effects of conventional therapy for BCR-ABL associated hematopoietic malignancies, and overcome drug-resistance.
ANATOMICAL CHARACTERISTICS OF ENDEMIC VERBASCUM BELLUM HUB. AND MOR. (SCROPHULARIACEAE)

Anadolu’da “Sigir kuyrugu” olarak adlandirilan Verbascum L. (Scrophulariaceae) cinsi, ulkemizde 194’u endemik olmak uzere 245 tur ile temsil edilmektedir. Cicekleri musilaj, ucucu yag ve glikozitler tasir. Bazi Verbascum turleri halk arasinda gogus yumusatici ve balgam sokturucu olarak, adet sancisini gidermede, yatistirici, romatizma agrilarini giderici ve hayvan yaralarini tedavi etmekte kullanilmaktadir. V. bellum Hub. Mor. turu, Akdeniz fitocografik bolgesinde yetisen ve ulkemize endemik bir turdur. V. bellum “Dirmil Sigirkuyrugu” turunun anatomik yapisi ilk kez bu calismada verilmis, fotograf ve cizimlerle desteklenmistir.
Can Cognitive and Perceptual Standardized Test Scores Predict Functional Performance in Adults Diagnosed with Stroke?: A Pilot Study

ABSTRACT Stroke is a major cause of disability worldwide, and typically leaves people with impaired cognitive and perceptual faculties. This pilot study assessed three standardized cognitive and visual perceptual assessments for their ability to predict functional performance in adults who have had a stroke—the Neurobehavioural Status Examination (Cognistat), Occupational Therapy Adult Perceptual Screening Test, and the Developmental Test of Visual Perception-Adolescent and Adult. The participants were 27 adults diagnosed as having had a stroke, who were admitted to an inpatient rehabilitation center over a nine-month period. The Functional Independence Measure (FIM) was used to measure their functional performance at discharge from rehabilitation. The results indicate that the “comprehension” and “similarities” subscales of the Cognistat were the best predictors of functional performance as measured by the FIM. A large amount of variance in functional performance remained unexplained by the standardized tests; however, overall and despite their limitations, the tests were able to predict functional performance skills of stroke patients.
The Development of the Catalog of Elective Subjects as a Means of Professional Training of Students

In this work the technology of the development of content of the elective courses as a way of professional training of students is theoretically proved. The development of the catalog of elective subjects - the process of drafting and detailing of professional knowledge of students, their experience of practical and creative activities in order to ensure the integrity and appropriateness of elective subjects . The development of the content elective courses is the process of developing and detailing the components of educational content based on the principles, sources of criteria reflecting the nature of the training of students. The backbone component of the content of elective courses in vocational training is the experience of creative design activity of students.Experience the creative activity of students is a combination of knowledge and practical skills mastered, formed in the process of training students to solve creative problems and issues. The development technology of the directory elective courses is an activity for the development of the content of each of the following modules: explanatory, basic, control and diagnostics. The criteria for the effectiveness of technology development directory elective courses as a means of training students are: The ratio of students to the content of elective subjects; teaching competence of the student; creative competence. (Zhaparova B.M., Tleulesova A.Sh., Sarsenbayeva B.G., Baygozhina Zh.M., Aytpayeva Zh.Zh., Sakenov D. Zh. The Development of the Catalog of Elective Subjects as a Means of Professional Training of Students. Life Sci J 2013;10(11s): 282-285). (ISSN:1097-8135). http://www.lifesciencesite. com . 50
EDITORIALS Validating and Improving Models for Projecting the Absolute Risk of Breast Cancer

In this issue of the Journal, Rockhill et al. (1) use data from 1992 to 1997 from white women in the Nurses’ Health Study (NHS) to address the validity and uses of the model of Gail et al. (2) for estimating breast cancer risk. One issue is how well the model predicts the risk of invasive breast cancer in various subgroups of women (“calibration”). A second issue is how sharply the model discriminates women who will develop breast cancer from those who will not (“discriminatory accuracy”). Rockhill et al. also comment on applications of the model. The model of Gail et al. (2) was based on follow-up of white women in the Breast Cancer Detection Demonstration Project (BCDDP). A nested case–control study in the BCDDP was used to estimate multivariate relative risks based on age at menarche, age at first live birth, number of first-degree relatives (mother and sisters) with breast cancer, number of breast biopsies, and whether or not atypical hyperplasia was present on any biopsy specimen. To estimate the absolute risk of developing breast cancer over a specified age interval, data from the case–control study were combined with age-specific breast cancer rates in the entire BCDDP cohort. Because BCDDP participants were screened annually with mammography, it was anticipated (2,3)
Characteristics of excellent Islamic education lecturers in teaching education institute of Malaysia

This article aims to discuss the excellent attitude that is practiced by Excellent Islamic Education Lecturer (EIEL) in Teacher Education Institute of Malaysia (TEIM). This excellent attitude is identified through one of a case study that was conducted earlier. This case study is implemented in Teacher Education Institute of Malaysia, Dato’ Razali Ismail Campus (TEIMDRIC) that involved comprehensive interview and observation with two EIEL and Head of Department, Department of Islamic Education and Moral Education. The result of this interview is then structured with NVivo 7.0 version to produce theme, model and matrix schedule related to the practice of excellent attitude of IEEL in Teacher Education Institute of Malaysia (TEIM). The result of the study showed that there are four aspects of excellent attitude that are practiced by EIEL during their duty in Teacher Education Institute of Malaysia. The aspects of excellent attitude are the features of outstanding attitude towards Allah, oneself, teacher trainers and colleagues. Key words: Attitude, excellent, lecturer.
Purificación de la hormona luteinizante (LH) en la lubina (Dicentrarchus labrax) y desarrollo de un inmunoensayo específico Purification of luteinizing hormone (LH) in the sea bass (Dicentrarchus labrax) and development of a specific immunoassay

The luteinizing hormone (LH) is a key regulator of the processes of gonad maturation, ovulation/spermiation and spawning in vertebrates. The present study describes the purification of LH from pituitaries of a teleost fish, the European sea bass (Dicentrarchus labrax), by three-step chromatography (gel filtration, ion-exchange and FPLC). The LH α and β subunits were isolated by rpHPLC. The molecular weight of LH was estimated, on SDS-PAGE, at 31 kD, and for its α and β subunits, at 12 and 22 kD, respectively. Specific antibodies against the sea bass LHβ subunit (AbLHβ) were obtained and used to develop a specific enzyme-linked immunosorbent assay (ELISA), which had a sensitivity of around 0.65 ng mL–1 (Bi/Bo 80%) and intraand inter-assay coefficients of variation of 11.7% (n = 8) and 11% (n = 10), respectively. Validation of the assay showed parallelism between the standard curve and plasma and pituitary samples from sea bass, as well as with pituitary extracts from other perciform fishes. We measured, using ELISA, plasma LH levels in female sea bass given a single injection of different doses of GnRHa ([D-Ala6, Pro9-Net]-LHRH), as a hormonal therapy for spawning induction. All treatments increased plasma LH levels after 90 min of the injection and were maintained elevated during 24 h. In conclusion, the immunoassay developed is sensitive and accurate, useful for LH analysis in biological samples of sea bass, and represents a valuable tool for studies on the reproductive endocrinology of this species.
RNAi-Mediated Silencing of p190Bcr-Abl Inactivates Stat5 and Cooperates with Imatinib Mesylate and 17-Allylamino-17-Demetoxygeldanamycin in Selective Killing of p190Bcr-Abl-Expressing Leukemia Cells.

The 190kD (p190) and 210kD (p210) Bcr-Abl proteins are responsible for the development and progression of Philadelphia chromosome (Ph)-positive leukemia. We applied RNA interference (RNAi) technology to specific killing of p190+ cells. After screening a series of small hairpin RNA (shRNA) targeting p190, we determined the optimal sequences for gene silencing in the BCR (shBCR), junctional (shE1A2) and ABL (shABL) region of p190, respectively. Then, p190+ (KOPN30), p210+ (K562) and both negative (HL60) cell lines were infected with lentiviral vectors encoding these shRNAs, resulting in an efficient killing of KOPN30 cells. K562 cells were also sensitive to the two other than junction-specific shRNA and none of the anti-p190 shRNAs could affect survival of HL-60 cells, although shABL appeared to have some inhibitory effects on their growth, suggesting that Abl may be positively involved in proliferation of HL60 cells. Furthermore, colony formation derived from CFU-GEMM, BFU-E and CFU-GM was not influenced by shBCR. On the contrary, CFU-GEMM and BFU-E-derived colony formation was significantly suppressed by shABL, suggesting that Abl may play a certain role especially in normal erythropoiesis. Nonetheless, anti-p190 shRNAs may become therapeutic options in Ph-ALL by improvement of their delivery system such as CD19-targeted liposome formulation which we previously developed. In p190-transformed Ba/F3 cells, RNAi-mediated silencing of p190 specifically inhibited tyrosine phospohorylation of stat5 prior to their death, but did not affect phosphorylation of either Jak2, Akt, MEK1/2 or ERK1/2. These results offer another evidence for the critical role of Stat5 in BCR-ABL-induced transformation of hematopoietic cells. It is likely that p190 directly phosphorylates Stat5 and that Jak2 is remote from activation of Stat5 in this cell context, although the possible involvement of Src family kinases such as Hck and Lyn has not been excluded. In contrast, down-regulation of p190 by their treatment with 17-allyl-amino-geldanamycin (17-AAG) was associated with reduced phosphorylation of not only Stat5 but also Jak2 and Akt. shRNA targeting p190 also collaborated additively with imatinib and 17-AAG in growth inhibition of Ba/F3-p190 and BaF/3-p190Y253H cells. Collectively, RNAi-mediated silencing of p190 is a promising option both for therapeutic application and for delineating signal transduction in p190-expressing leukemia.
Cross-cultural adaptation and psychometric properties of the Lithuanian version of the Simple Shoulder Test

Materials and methods. The SST was culturally adapted following recommendations of American Academy of Orthopaedic Surgeons. Psychometric properties of the SST-LT were determined for preoperative patient group with rotator cuff injury (n = 108), and for the ambula tory patient group (80 of the 108 preoperative patients) after surgery. Results. The internal consistency in both groups was not high (Cronbach’s alpha 0.722 and 0.844). Intraclass correlation coefficient for test-retest reliability was 0.96 with the 95% con fidence interval (0.94–0.98). The SST-LT scores were compared with the Lithuanian SF36v2 and the Constant scoring scale. Correlations between the SST-LT scores, patient-based and observer-based measures were from 0.492 to 0.881 (p < 0.001). Conclusion. The SST-LT can be used as shoulder joint specific and office-based patient selfassessment tool for the Lithuanian speaking population.
Computerized algorithm for baseline estimation of fetal heart rate

On the present work we propose an algorithm that after unstable segments identification by the first derivative estimates the baseline of antepartum fetal cardiotachograms. Therefore, 50 records 5 minutes long, derived from abdominal ECG, were processed according to the methods of Dawes (1981), Mantel (1990), and our proposal. Besides visual analysis, statistical differences among methods were established More appropriate visual fits of the baseline were gotten by our proposal (76%) than Mantel (22%) and Dawes (2%). Since lower mean baseline was computed from Mantel (137.8/spl plusmn/8.4 hpm) than from Dawes (140.4/spl plusmn/8.4 bpm) and our proposal (140.0/spl plusmn/8.4 bpm), different account for accelerations and decelerations were also found Our proposal showed advantages to estimate the baseline of cardiotachograms as it was properly adjusted at the beginning of the traces depended of only 15 seconds of valid segments an corresponded more closely to the visual baseline.
Missense Mutations in the ABCB6 Transporter Cause Dominant Familial Pseudohyperkalemia

Abstract 3184 Isolated Familial Pseudohyperkalemia (FP) is a dominant red cell trait characterized by cold-induced slow ‘passive leak’ of red cell K + into plasma, first described in a large Scottish family from Edinburgh (Stewart GW, et al., 1979) . Although in freshly obtained blood samples plasma [K + ] was normal, it was increased when measured in blood stored at or below room temperature. This trait was unaccompanied by clinical symptoms or signs except for mild abnormalities of red cell shape. FP Lille was later described in a large Flemish kindred with morphologically normal red cells (Dagher G, et al., 1989; Vantyghem MC, et al., 1991). In this family, red cell K + efflux measured in the presence of ouabain and bumetanide was normal at 37°C, but greatly increased at 22°C and 9°C. FP Lille mapped to 2q35-q36 (Carella M, et al., 2004) , whereas FP Edinburgh mapped to 16q23-qter (Iolascon A, et al., 1999). Subsequently, asymptomatic cases FP Chiswick and FP Falkirk with remarkable increased MCV were reported (Haines PG, et al., 2001). Functional gene mapping and sequencing analysis of the candidate genes within the 2q35-q36 critical interval in three multigenerational FP families with 20 affected individuals identified two novel heterozygous missense mutations in the ABCB6 gene that cosegregated with disease phenotype. The two genomic substitutions altered two adjacent nucleotides within codon 375 of ABCB6, a porphyrin transporter that in erythrocyte membranes bears the Langereis blood group antigen system (Krishnamurthy PC, et al., 2006; Helias V, et al., 2012). Structural modeling predicts subtle changes in protein structure associated with either mutation. ABCB6 mRNA and protein levels increased during erythroid differentiation of CD34+ erythroid precursors (at 7 and 14 days of EPO induced differentiation), and of HEL and K562 erythroleukemia cells. However, the ABCB6 R375Q mutation altered neither levels of ABCB6 mRNA or protein, nor protein localization in mature erythrocytes or erythroid precursor cells. These data strongly suggest that missense mutations in residue 375 of the ABCB6 polypeptide either mediate the cold-induced K + leak of chromosome 2-linked FP, or activate an independent, cold-induced cation permeability pathway of the red cell. Disclosures: No relevant conflicts of interest to declare.
A PROPOSED METHODOLOGY FOR THE CORRECTION OF THE LEAF AREA INDEX MEASURED WITH A CEPTOMETER FOR PINUS AND EUCALYPTUS FORESTS

Leaf area index (LAI) is an important parameter controlling many biological and physiological processes associated with vegetation on the Earth's surface, such as photosynthesis, respiration, transpiration, carbon and nutrient cycle and rainfall interception. LAI can be measured indirectly by sunfleck ceptometers in an easy and non-destructive way but this practical methodology tends to underestimated when measured by these instruments. Trying to correct this underestimation, some previous studies heave proposed the multiplication of the observed LAI value by a constant correction factor. The assumption of this work is LAI obtained from the allometric equations are not so problematic and can be used as a reference LAI to develop a new methodology to correct the ceptometer one. This new methodology indicates that the bias (the difference between the ceptometer and the reference LAI) is estimated as a function of the basal area per unit ground area and that bias is summed to the measured value. This study has proved that while the measured Pinus LAI needs a correction, there is no need for that correction for the Eucalyptus LAI. However, even for this last specie the proposed methodology gives closer estimations to the real LAI values.
The Dynamics of Physical and Mental Health

Mental and physical aspects are both integral to health but little is known about the dynamic relationship between them. We consider the dynamic relationship between mental and physical health using a sample of 10,339 individuals in six waves (2002-2013) of the English Longitudinal Study of Ageing (ELSA). We estimate linear and non-linear random-effects regression models to identify the effects of past physical health, measured by Activities of Daily Living (ADL), and past mental health, measured by the Centre for Epidemiological Studies Depression (CES-D) scale, on both present physical and mental health. We find that both mental and physical health are moderately state-dependent and explain 0.2% of the unobserved heterogeneity in health. Worse past mental health significantly decreases present physical health (-0.036 coefficient-value). Better past physical health significantly increases present mental health (-0.266 coefficient-value). These cross-effects are non-linear and suggest that health policies aimed at specific aspects of health have to consider potential spill-over effects.
USE OF ELECTRONIC RESOURCES BY POSTGRADUATE STUDENTS OF THE INSTITUTE FOR FINANCIAL MANAGEMENT AND RESEARCH (IFMR), CHENNAI, INDIA.

The paper focuses on use of electronic resources in the H.T. Parekh library of the Institute for Financial Management and Research (IFMR), Chennai. It highlights the use of e-resources by post graduate students of IFMR business school. An attempt is made to identify which electronic information resources are more useful to the students in various formats like CD-ROM and DVD-ROM databases, On-line databases, E-journals and plenty of Internet / Web resources. It will also x-ray the problems associated with the use of electronic resources. Attempts have been made to know the differences in use of electronic resources between first and second year students of IFMR B-School and finally to make recommendations to improve the present state of usage of electronic resources in IFMR, Chennai.
A Strategy for Large-Scale Systematic Pan-Cancer Germline Rare Variation Analysis

Traditionally, genetic studies in cancer are focused on somatic mutations found in tumors and absent from the normal tissue. However, this approach omits inherited component of the cancer risk. We assembled exome sequences from about 2,000 patients with different types of cancers: breast cancer, colon cancer and cutaneous and ocular melanomas matched to more than 7,000 non-cancer controls. Using this dataset, we described germline variation in the known cancer genes grouped by inheritance mode or inclusion in a known cancer pathway. According to our observations, protein-truncating singleton variants in loss-of-function tolerant genes following autosomal dominant inheritance mode are driving the association signal in both genetically enriched and unselected cancer cases. We also performed separate gene-based association analysis for individual phenotypes and proposed a list of new cancer risk gene candidates. Taken together, these results extend existing knowledge of germline variation contribution to cancer onset and provide a strategy for novel gene discovery.