Miracle-dz/UniFAR-FTUs huggingface dataset:
pp60c‐src mediates ERK activation/nuclear localization and PAI‐1 gene expression in response to cellular deformation

Release of transcellular tension upon disruption of actin stress fibers with cytochalasin D (CD) and associated changes in cell morphology are reflected in the rapid transcription of “deformation‐responsive” genes. For certain genes (e.g., urokinase plasminogen activator and its type‐1 inhibitor PAI‐1), de novo mRNA synthesis appears to require cell shape‐dependent activation of the MAP kinases ERK1/2. ERK activation in response to microfilament disruption was inhibited completely by the broad‐spectrum tyrosine kinase inhibitor genistein and the relatively src‐kinase selective compound PP1. Such inhibitor sensitivity profiles suggested that src‐family members, likely pp60c‐src, were important upstream elements in deformation‐related ERK activation. pp60c‐src kinase activity was elevated fourfold within 15 min after CD addition to quiescent R22 smooth muscle cells and declined quickly thereafter. CD‐induced increases in the phosphorylation levels of both pp60c‐src and IgG heavy chain (a substrate target in the coupled immunoprecipitation/in vitro pp60c‐src kinase assay) were ablated completely by pretreatment with the src‐type kinase inhibitor PP1. Prior PP1 exposure similarly repressed CD‐stimulated PAI‐1 transcript accumulation. Consistent with the pharmacologic findings, transfection of a dominant‐negative pp60c‐src expression construct (DN‐Src) effectively suppressed (in a concentration‐dependent manner) CD‐induced PAI‐1 synthesis in R22 cells. To more specifically address the potential involvement of src kinases in CD‐initiated ERK mobilization, R22 cells were transiently co‐transfected with DN‐Src and Myc‐tagged ERK2 expression constructs, serum‐deprived then stimulated with CD. The effect of DN‐Src expression on endogenous ERK1/2 activation and nuclear translocation was assessed in separate experiments. The phosphorylation levels of both exogenous (Myc‐ERK2) and endogenous ERK1/2 targets was significantly reduced by DN‐Src; nuclear accumulation of pERK1/2 was completely inhibited. These data indicate that pp60c‐src is a critical upstream activator of the ERK cascade leading to PAI‐1 transcription in response to cellular deformation stimuli. © 2003 Wiley‐Liss, Inc.
Bio-informatique pour la génomique et le diagnostic des maladies infectieuses

Sequencing a genome is a milestone in the study of an organism. Bioinformatics allow both to better understand single organisms and to compare them to related species through comparative genomics. This thesis centers on the idea that genome sequence of parasites and viruses can be used in various ways to better understand these microorganisms. Transcriptomics and comparative genomics were used to study the protozoan parasite Leishmania in order to better understand its virulence, its resistance to antiparasitic drugs, and its dimorphic life-cycle, which includes a flagellated free form named promastigote and an aflagellate intracellular form named amastigote. In order to study gene expression in Leishmania, an integrated management and analysis system was created, along with protocols designed for Leishmania microarrays analysis. Four studies using this system are briefly described. In another study, the genome of Leishmania (sauroleishmania) tarentolae, a lizard parasite, was sequenced and compared to human pathogenic Leishmania species. This study showed little difference between the Leishmania species, although L. tarentolae seems to contain less genes associated to the amastigote life-cycle, including the amastin gene. Two gene families were highly expanded in L. tarentolae: the surface metalloprotease GP63 and the promastigote antigen protein PSA31C. These results provide a better understanding of L. tarentolae biology and give insights on the genes involved in virulence in pathogenic Leishmania species. The second part of this thesis concerns the creation of a molecular diagnostic assay for the detection and identification of 25 respiratory virus types, including the influenza A/H1N1 pandemic strain and the avian influenza A/H5N1 strain. This assay was created by analyzing genome sequences available from public repositories and it was afterwards tested on laboratory and clinical virus strains. Although Leishmania and respiratory viruses are distantly related, the approaches used in both projects were similar. Thus, bioinformatics is an essential and ubiquitous science that allows to solve problems in different areas (―omics‖) of biology.
Influence of irrigation, nitrogen and zinc on productivity and water use by late sown wheat (Triticum aestivum)

A field experiment was conducted on deep sandy soil (Typic Ustochrept) at the Water Technology Centre, In dian Agricultural Research Institute, New Delhi, during winter seasons of 1999 2000 and 2000 2001 with late sown HD 2285 wheat (Trticum aestivum L. emend. Fiori Paol.). The treatments comprising 4 irrigation levels [I,, no post sowing irrigation I,, 1 irrigation at crown root intiation (CRI) stage I , 2 irrigations, each at CRI and flower ing stages I, 4 irrigation each given at CRI, jointing, flowering and dough stages] in main plots and combinations of 3 N levels (0, 50 and 100 kg Nlha) and 2 zinc levels (0 and 5 kg Znlha) in subplots were laid out in split design, replicated 3 times, to find out the influence of irrigation, nitrogen, zinc and their interactions on yield and moisture use by the crop. Progressive increase in irrigations from 0 to 4 and N levels from 0 to 100 kg/ha, increased wheat yield attributes and grain yield significantly over the control rteatrnents (loand No). The average seasonal consump tive water use (CU) by wheat increased with every additional irrigation level to a maximum of 328.4 mm and 301.7 mm in the first and second season respectively. On an average (2 seasons), water use efficiency (WUE) was the highest (1 38 kg grain/m3) with I,. However, the straw yield (6,808.5 kglha) and grain yield (3,962.5 kg/ha) were highest with I , . The average moisture use rate increased with increase in irrigation to a maximum of 2.63 mmlday. Maximum moisture extraction of 59.4 to 65.8 % was from the 0 3 0 cm and the minimum (7.10 to 5.32%) from the 90 120 cm soil depth. The WUE increased markedly with the increase in N level.
The relationship among gratitude, hope, connections, and innovativeness

ABSTRACT The interwoven relationships among positive emotions and connections among people within the organization, manifested as collective gratitude and hope, and high-quality connections (HQCs), and firm service innovativeness and financial performance have rarely been addressed in the service innovation management literature. By studying 251 service firms, this paper shows that (a) collective gratitude is positively related to development of HQCs among people within the organization and firm service innovativeness, (b) HQCs among people within the organization are positively associated with firm service innovativeness, and (c) firm service innovativeness is positively related to firm financial performance. This paper also demonstrates that the collective hope of people within the organization positively moderates the relationship between collective gratitude and HQCs among them.
The dynamic relationships between stock index futures and stock index markets: Evidence from China

This paper employs the VAR-MGARCH models to investigate the price causal relationships and volatility spillovers effects between the CSI 300 index futures and spot markets in China. The 5 min high-frequency data from January 4, 2013 to October 31, 2013 are used. Four different multivariate GARCH models (BEKK, diagonal, constant conditional correlation, and dynamic conditional correlation) are compared and contrasted. It is found that the VAR-DCC-MGARCH model fits the data best and generates results showing that there exist bidirectional price causal relationships between the CSI 300 index futures and spot markets and the CSI 300 futures market tends to play a more dominant role in the price discovery process; there exist bidirectional volatility spillovers effects between the two markets and the index futures and spot markets play the almost equal roles in the volatility information transmission; the CSI 300 index futures and spot markets show a very strong linkage and the dynamic conditional correlations vary from 0.479 to 0.959 with time change. These conclusions indicate that at the maturity stage, the price discovery function of the CSI 300 index futures market has worked well, and the operating efficiency of the CSI 300 index futures market has further improved.
Acceptance of noise growth patterns in hearing aid users.

PURPOSE To examine whether the effects of speech presentation level on acceptance of noise could differentiate full-time, part-time, and nonusers of hearing aids and whether these effects could predict hearing aid use. METHOD Participants were separated into 3 groups on the basis of hearing aid use: (a) full-time use, (b) part-time use, or (c) nonuse. Acceptable noise levels (ANLs) were measured conventionally and at 8 fixed presentation levels. The effects of presentation level on ANL were determined by calculating global ANL (ANL averaged across presentation level) and ANL growth (slope of the ANL function). RESULTS Global ANLs were smaller for full-time users than for part-time users and nonusers; however, global ANLs were not different for part-time users and nonusers. ANL growth differentiated full-time users from nonusers only. Conventional ANL predicted hearing aid use with 68% accuracy. Compared with conventional ANL, the accuracy of the prediction for global ANL and ANL growth decreased, and the accuracy of the prediction at presentation levels of 65 to 75 dB HL was maintained. CONCLUSIONS Global ANL differentiated the hearing aid groups in the same manner as conventional ANL. The effects of presentation level on acceptance of noise did not considerably increase the accuracy of the prediction compared with conventional ANL. Clinical applications are discussed.
Financial Literacy and Its Consequences in the Emerging Middle Class

This paper analyzes the state and impact of financial literacy in a so far largely neglected group: the middle class in emerging economies. This group is of increasing importance for implementing structural change, including the proper use of sophisticated financial products. We survey middle class people living in Bangkok and find that higher financial literacy leads to an increased probability of individuals demanding the sophisticated financial products that are available, and more informed use of credit cards. Overall, improving the financial literacy of the emerging middle class provides a double dividend: it increases the welfare of this group and also contributes to financial development, which is a driver of growth.
Efficacy of intravenous dexmedetomidine on patient's satisfaction, comfort and sedation during awake fibre-optic intubation in patients with cervical spondylotic myelopathy posted for elective cervical fixation

Background and Aims: Various anaesthetic drugs, in addition to airway block, are used for producing favourable intubation conditions during awake fibre-optic intubation (AFOI), but most of them cause respiratory depression and hypoxaemia. The aim of this study was to evaluate the efficacy of intravenous (IV) dexmedetomidine (DEX) on sedation, patient comfort and cardiovascular responses during AFOI in patients with cervical spondylotic myelopathy (CSM). Methods: This randomised, placebo-controlled, double-blinded, prospective study was conducted on 56 adult patients with cervical spondylotic myelopathy (CSM) undergoing elective cervical fixation, who were randomly allocated into two groups - Group D and Group C. Group D patients received DEX infusion at a rate of 1 μg/kg for the first 10 min followed by 0.5 μg/kg/h and Group C received 0.9% normal saline infusion in the same manner. Airway blocks with lignocaine were given to all patients before undergoing AFOI. Patient's alertness, sedation and cardiorespiratory changes during the procedure were assessed by the Observer Assessment Awareness and Sedation (OAA/S) scale. On the 1st post-operative day, patient's' comfort during AFOI was assessed by visual analogue scale (VAS). Results: Patients of Group D had an acceptable level of sedation (OAA/S score: 20 to 17 with greater comfort and satisfaction (VAS: 40–60), compared to control group (VAS: 50–90, P < 0.001.). Moreover, haemodynamic parameters were less significantly altered in the DEX group during AFOI. Conclusions: IV DEX infusion during AFOI improves patient's tolerances with an acceptable level of sedation without significant haemodynamic instability and respiratory depression.
Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C?

BACKGROUND Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs. METHODS Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 microg/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals. RESULTS There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P<0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dt(max)) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12+/-8% of baseline), in contrast to those that received isoflurane (75+/-7% recovery). Bisindolylmaleimide at a dose of 2 microg/min alone enhanced recovery of segment shortening (50+/-7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 microg/min bisindolylmaleimide further enhanced recovery of contractile function (79+/-8% of baseline). In contrast, 8 microg/min bisindolylmaleimide alone (32+/-12%) or combined with isoflurane (37+/-17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs. CONCLUSIONS The results indicate that protein kinase C inhibition using low doses of bisindolylmaleimide alone produces cardioprotection, and isoflurane further enhances this protection. In contrast, high doses of bisindolylmaleimide are not cardioprotective in the presence or absence of isoflurane. A role for protein kinase C during isoflurane-induced recovery of the stunned myocardium cannot be excluded.
PROMOTION OF INCOMPATIBLE ALLOGRAFT ACCEPTANCE IN RHESUS MONKEYS GIVEN POSTTRANSPLANT ANTITHYMOCYTE GLOBULIN AND DONOR BONE MARROW: I. In Vivo Parameters and Immunohistologic Evidence Suggesting Microchimerism

This report extends previous studies demonstrating that prolonged acceptance of incompatible kidney allo-grafts in rhesus monkeys can be achieved by a short recipient rabbit antithymocyte globulin (RATG) treatment course followed by donor bone marrow infusion on day 12 without a requirement for chronic immune-suppression. Serial studies of antilymphocyte cyctotoxic antibody in recipients' sera following RATG injections showed pan-lymphocyte-reactive antibody present until day 10 posttransplant. On days 11 and 12, pan-lymphocyte-reactive antibody was no longer detectable, but cytotoxic antibody specific for mature T cells remained in recipients' sera. These findings might explain the critical time relationship between antithymocyte globulin treatment and donor bone marrow infusion, and further suggest that the tolerance-promoting cell in donor bone marrow is not a mature T cell, but rather a pre-T or a non-T cell. Finally, it was found that this treatment protocol resulted in development of lymphoid nodules in the transplanted kidney that express a CD8-positive, FcIgG-receptor-positive phenotype and appear to be of donor origin. The possibility of a veto cell type of mechanism is discussed as an explanation for the promotion of allograft acceptance in this model.
tp53-dependent G2 arrest mediator candidate gene, Reprimo, is down-regulated by promoter hypermethylation in pediatric acute myeloid leukemia

Reprimo (RPRM) is a novel tumor suppressor. However, the expression and molecular function of RPRM in pediatric acute myeloid leukemia (AML) is still unknown. We observed hypermethylation of the RPRM promoter in 8/11 leukemia cell lines and in 44.8% (47/105) of pediatric AML samples compared with 6.7% (2/30) of control samples. Bisulfite genomic sequencing analysis showed that the RPRM promoter was methylated in the majority of AML samples (66.2–83.1%), whereas RPRM was almost unmethylated in normal bone marrow samples (20.0–27.7%). Kaplan–Meier survival analysis revealed poor survival outcomes in samples with RPRM promoter methylation (p < 0.001). Proliferation of AML cells was inhibited in a dose-dependent manner (p < 0.05) after RPRM overexpression with lentivirus transfection. Apoptosis was up-regulated in RPRM-overexpressing AML cells. Real-time polymerase chain reaction array analysis revealed 50 dysregulated genes that might be implicated in apoptosis of RPRM-induced AML cells. RPRM may be a putative tumor suppressor in pediatric AML.
Retrovirally induced switch from production of IL‐12 to IL‐4 in dendritic cells

Dendritic cells (DC) in HIV‐1 infection show a reduced capacity to stimulate primary T cell proliferation. Exposure of bone marrow‐derived DC to Rauscher leukemia virus (RLV) provides a mouse model for studying retrovirally induced reduction in stimulatory capacity for T cells. Treatment with IL‐12, a cytokine that promotes the development of Th1 cells, has been postulated as a treatment for AIDS and is effective at restoring cell‐mediated immunity in mice infected with mouse AIDS virus or with RLV (see Knight, S. C. and Patterson, S., Annu. Rev. Immunol. 1994. 15: 593 – 615 for references). Here we studied the direct effect of RLV and of IL‐12 on bone marrow‐derived DC. Normal DC produced IL‐12 and IL‐10 and stimulated primary allogeneic T cell proliferation. Exposure of DC to RLV caused reduced production of IL‐12, production of IL‐4 was seen in DC for the first time and T cell stimulation was inhibited. Addition of IL‐12 reinstated and enhanced IL‐12 synthesis in RLV‐treated DC, abrogated production of IL‐10 and IL‐4 and restored stimulatory activity. Manipulation of cytokine production in DC could be a stratagem that has evolved in the retrovirus to avoid stimulation of cellular responses.
Accounting for China's Saving‐Investment Imbalance from 2002–2008

This paper decomposes and analyzes China's saving-investment imbalance (equivalent to current account imbalance) from 2002–2008. We first use the Flow of Funds Accounts to calculate the saving and investment rates (propensity) of the household, corporate and government sectors and to evaluate their relative contribution to the aggregate saving-investment surplus. The results indicate that the increase of saving-investment surplus can be attributed to the steady increase of saving by the household and government sectors and the short-term downsizing of investment by the corporate and government sectors. We then use more disaggregate supplementary datasets to explore the factors behind the evolution of the saving and investment rates for the three sectors. The rise of the household saving rate mainly sources from the urban sector. The corporate saving rate experienced a steady increase because of the rise of profitability. Government macroeconomic policies have had a strong influence on the saving and investment patterns of the corporate and government sectors.
Similarity and difference in tumor-infiltrating lymphocytes in original tumor tissues and those of in vitro expanded populations in head and neck cancer

Though adoptive tumor-infiltrating lymphocyte (TIL) therapy has been explored in clinical trials for many years, there is little information for the clonotype composition between TILs in original tumor tissues and TILs that were in vitro expanded and infused to cancer patients. To investigate the similarity/difference in TILs in original tumor tissues and those of in vitro expanded populations in squamous cell carcinoma of head and neck (SCCHN) as well as their correlation with somatic mutations in cancer cells, we performed whole exome analysis, expression profile analysis of immune-related genes, and T cell receptor (TCR) analysis of original TILs and in vitro expanded TILs in 8 surgically-resected HPV-negative fresh tumors with SCCHN. We found an unusually high number of non-synonymous somatic mutations (4290, 1779 and 901 mutations) in three SCCHN tumors, in which we identified mutations in mismatch repair genes, MSH2 or MSH4, or a DNA polymerase gene, POLE. Interestingly, dominant TCR clonotypes of expanded CD8+ TILs derived from these three tumors revealed high similarity to those in original tumors while for remaining tumors with the lower mutational load, we found that T cell clonotypes between TILs in original tumor tissues and those expanded in vitro were almost entirely different. Our findings might provide clinically useful information for identification of tumor-antigen-specific T cell clones that may lead to further improvement of adoptive TIL therapy for SCCHN patients.
Prognostic relevance of motor tests in elite girls’ soccer: a five-year prospective cohort study within the German talent promotion program

ABSTRACT Introduction: While research has provided valuable information about talent predictors, there is a gap regarding female soccer. This study analyzed the prognostic relevance of motor tests for players’ future selection level in female soccer and assessed the role of sex as a moderator variable. Methods: Within the German talent promotion program, N = 499 U12 girls participated in motor diagnostics (sprint, agility, dribbling, ball control, shooting). Five years later, 14.2% of them made the youth national team (NT), 18.8% the regional association team (RA), and 66.9% were not further selected (NS). The tests’ predictive validity for achieving one of these levels was analyzed using ANOVAs with post-hoc tests and logistic regressions. Subsequently, results were compared to data from previous research with N = 22,843 male U12 players. Results: Girls’ performances in the motor diagnostics significantly discriminated between all three selection levels. Future NT players outperformed NS (d = 1.04) and RA players (d = 0.55), who, in turn, performed better than NS players (d = 0.47). Exception for dribbling, the motor tests demonstrated predictive validity independent of sex. Discussion: Although diagnostics are not sensitive enough to determine individual decisions for talent selection, they provide objective information to supplement coaches’ work.