Miracle-dz/UniFAR-FTUs huggingface dataset:
Hematin-derived anticoagulant. Generation in vitro and in vivo

Prolongation of clotting times produced by hematin was investigated both in vitro and in vivo. Hematin-derived anticoagulant (HDA) was found to be due to a degradative product or derivative of hematin, and was generated in vitro in standing (aging) aqueous solutions of the parent compound. Generation of HDA in vitro was inhibited by antioxidants. The anticoagulant effect of HDA was inhibited by freshly prepared hematin, fresh Sn-protoporphyrin, imidazole, or the iron chelator desferrioxamine. Ferrioxamine did not inhibit HDA, and inhibition by imidazole was reversed with ferric citrate, suggesting a role for iron in the mechanism of HDA activity. HDA activity was dissociated from hematin in plasma by clotting with thrombin. HDA segregated into the clot fraction, whereas hematin remained largely in the serum fraction, suggesting that HDA may preferentially bind to fibrinogen. TLC and HPLC showed a single peak of HDA activity that was not associated with the parent compound. Evidence for HDA generation in vivo was found when rats were injected with fresh (no HDA) hematin. Prolongation of clotting times appeared after hematin appeared in the plasma, and anticoagulant activity persisted after a fall in plasma hematin concentration. Thus, there was a temporal dissociation between hematin and HDA, suggesting that a modification of hematin must occur in vivo before an anticoagulant effect is produced. Generation of HDA in vitro has implications for hematin preparation and administration. Generation of HDA in vivo suggests that similar modifications of endogenous heme or other porphyrins may occur to produce HDA under physiologic or pathophysiologic conditions.
The anti-proliferative effect of calcitriol on HL-60 cells is neutralized by uraemic biological fluids.

BACKGROUND It has been demonstrated that uraemic serum/ultrafiltrate inhibits cell-mediated immune response in vitro, and that it suppresses calcitriol synthesis and its biological actions. METHODS In the present in vitro study, the effect of calcitriol, uraemic ultrafiltrate (UUF) and a combination of both on the human promyelocytic leukaemia cell line, HL-60, was studied by evaluating bromodeoxyuridine (BrdU) incorporation into the DNA, luminol-amplified chemiluminescence (CL) production, expression of CD14, and levels of vitamin D receptor mRNA (VDR mRNA) and CD14 mRNA. RESULTS The ability of calcitriol to block cell proliferation (37.4+/-5.4 to 30.5+/-5.6% cells incorporating BrdU, P:<0.01) was neutralized when UUF was applied together with calcitriol (53.4+/-21.3% cells incorporating BrdU, P:<0.01 vs calcitriol alone). Similarly to what was observed for BrdU incorporation, the CL production of HL-60 cells was enhanced in the presence of calcitriol (20126+/-10154 to 61528+/-24021 cpm, P:<0.01), and was suppressed again in the presence of calcitriol and UUF (20916+/-12075 cpm, P:<0.01 vs calcitriol alone); finally UUF also inhibited the calcitriol-induced CD14 expression (71.1+/-11.2 to 54.9+/-17.7% CD14 positive cells, P:<0.05). On the other hand, the calcitriol-induced CD14 mRNA levels were not significantly different in the presence of calcitriol and UUF compared to calcitriol alone. This points to an inhibition by UUF at a post-transcriptional level. Similar data were found for VDR mRNA levels. UUF was fractionated by HPLC in four fractions, hydrophilic uraemic solutes being eluted first (F1) and hydrophobic solutes being eluted last (F4); fractions 1, 2 and 3 simultaneously affected both BrdU incorporation and CL production in a significant way. CONCLUSIONS It is concluded that UUF contains factors that impair calcitriol-activated function of HL-60 cells. Hence, the differentiation and immune response of these promyelocytic leukaemia cells, as induced by the supplementation of calcitriol, is neutralized in the presence of uraemic biological fluids. This may be of relevance for the propensity to infection and malignancy of the uraemic patient.
Psychologic response to colectomy. II. Adjustment to a permanent colostomy.

IN A PREVIOUS article 1 we reported on an investigation of the adaptation patients make to a total colectomy and the resulting abdominal stoma. This group was composed of 41 patients with chronic ulcerative colitis who eventually required colectomy and a permanent ileostomy. The findings indicated that the overall state of health and function was excellent. Most patients felt that the ileostomy was preferable to living with severe ulcerative colitis: the operation was perceived as a relief, not as a burden. Manifestations of emotional problems were less evident than would be expected, due to freedom from the debility and diarrhea that had existed for many years. Half of the group, however, described problems with their ileostomy such as fear of "accidents," odor, "straining," or sexual difficulties. In order to understand these problems more fully, it was decided to study another group of patients with intestinal stomas: those with colostomies following surgery
Structural insights into recognition and repair of UV-DNA damage by Spore Photoproduct Lyase, a radical SAM enzyme

Bacterial spores possess an enormous resistance to ultraviolet (UV) radiation. This is largely due to a unique DNA repair enzyme, Spore Photoproduct Lyase (SP lyase) that repairs a specific UV-induced DNA lesion, the spore photoproduct (SP), through an unprecedented radical-based mechanism. Unlike DNA photolyases, SP lyase belongs to the emerging superfamily of radical S-adenosyl-l-methionine (SAM) enzymes and uses a [4Fe–4S]1+ cluster and SAM to initiate the repair reaction. We report here the first crystal structure of this enigmatic enzyme in complex with its [4Fe–4S] cluster and its SAM cofactor, in the absence and presence of a DNA lesion, the dinucleoside SP. The high resolution structures provide fundamental insights into the active site, the DNA lesion recognition and binding which involve a β-hairpin structure. We show that SAM and a conserved cysteine residue are perfectly positioned in the active site for hydrogen atom abstraction from the dihydrothymine residue of the lesion and donation to the α-thyminyl radical moiety, respectively. Based on structural and biochemical characterizations of mutant proteins, we substantiate the role of this cysteine in the enzymatic mechanism. Our structure reveals how SP lyase combines specific features of radical SAM and DNA repair enzymes to enable a complex radical-based repair reaction to take place.
Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study

Objectives: Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFα) blocking therapy. Methods: This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. Results: Sixteen patients (13 women) were studied; all had previously failed TNFα-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p<0.01 indicating a significant treatment effect), with particular reduction in IFNγ of −52% (95% CI −73 to −15, p<0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE–MRI showed a reduction of 15–40% in MRI parameters. Conclusion: These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.
Differential targeting of androgen and glucocorticoid receptors induces ER stress and apoptosis in prostate cancer cells

Androgen (AR) and glucocorticoid (GR) receptor signaling play opposing roles in prostate tumorigenesis: in prostate, AR acts as an oncogene, and GR is a tumor suppressor. Recently, we found that non-steroidal phyto-chemical Compound A (CpdA) is AR/GR modulator acting as anti-inflammatory anti-androgen. CpdA inhibits AR and prevents GR transactivation while enhancing GR transrepression. GR and AR are controlled by proteasomal degradation. We found that prolonged exposure of LNCaP, LNCaP-GR, DU145 and PC3 prostate carcinoma (PCa) cells to proteasome inhibitor Bortezomib (BZ) caused AR degradation and GR accumulation. BZ enhanced CpdA ability to inhibit AR and to augment GR transrepression. We also found that CpdA+BZ differentially regulated GR/AR to cooperatively suppress PCa cell growth and survival and to induce endoplasmic reticulum stress (ERS). Importantly, CpdA+BZ differentially regulated GR-responsive genes. CpdA+BZ blocked activation of glucocorticoid-responsive pro-survival genes, including SGK1, but activated BZ-induced ERS-related genes BIP/HSPA5 and CHOP /GADD153. Using ChIP, we showed that SGK1, BIP/HSPA5 and CHOP regulation was due to effects of CpdA and CpdA+BZ on GR loading on their promoters. We also found that AR and GR are abundant in advanced PCa from patients treated by androgen ablation and/or chemotherapy: 56% of carcinomas from treated patients expressed both receptors, and the other 27% expressed either GR or AR. Overall, our data validate the concept of dual AR/GR targeting in prostate cancer (PC) and suggest that BZ combination with dual-target steroid receptor modulator CpdA has high potential for PC therapy.
SLEEP PATTERNS IN CHILDREN AND YOUNG ADULTS WITH MENTAL RETARDATION AND SEVERE BEHAVIOR DISORDERS

The 24‐hour sleep‐wake schedules of 51 individuals (age 3 to 21 years) with mental retardation and severe behavior disorders were recorded using a direct‐observation data collection system over an average period of approximately one month. The patients in the study had significantly less total sleep and less night sleep than their peers of the same age, and 88% had disturbances of sleep:delays in getting to sleep, frequent night waking or early waking. ‘Appropriate’ sleep, a measure of the amount and regularity of sleep, correlated positively with standardized measures of IQ and expressive language. ‘Total’ sleep, that is, the overall number of hours, was not correlated with measures of cognitive functioning. The findings are compared with those from other studies describing the sleep of individuals with mental retardation.
Understanding emotional reactions to a suspenseful movie: The interaction between forewarning and preferred coping style

An experiment is reported that tested the notion that the effects of forewarning to a suspenseful film are dependent upon one's preferred way of coping with stressful events. Preferred coping style was assessed with the MBSS (Miller Behavioral Style Scale) that classifies individuals as either high monitors/low blunters or high blunters/low monitors. Research participants of each type were exposed to a suspenseful film clip from the movie When A Stranger Calls, after receiving either a low or high amount of information about the events in the film. The hypothesis was that high monitors/low blunters would prefer the high forewarning to the low forewarning and would react more negatively in the low forewarning condition. High blunters/low monitors were expected to prefer the low forewarning to the high forewarning and were expected to react more negatively in the high forewarning condition. Emotional responses were measured with self‐reports, skin conductivity, and thought listings. Support for the hypothes.
VEGA: Visible spEctroGraph and polArimeter for the CHARA array: principle and performance

Context. Among optical stellar interferometers, the CHARA Array located at Mt Wilson in California offers the potential of very long baselines (up to 330 m) and the prospect of coupling multiple beam combiners. This paper presents the principle and the measured performance of VEGA, Visible spEctroGraph and polArimeter installed in September 2007 at the coherent focus of the array. Aims. With 0.3 ms of arc of spatial resolution and up to $30 000$ of spectral resolution, VEGA intends to measure fundamental parameters of stars, to study stellar activities and to image and analyze circumstellar environments. We describe the observing modes that have been implemented for this spectro-polarimeter and show actual performances measured on the sky during the first observing runs. Methods. The astrophysical programs are described in relation to the observing modes of the instrument, the presentation of the spectrograph and of the interface table is shown and finally the data is presented. We discuss the perspectives of further development in the framework of the CHARA Array. Results. We show that VEGA/CHARA is fully operational. The current limiting magnitude is nearly 7 but the results depend on the observing conditions (seeing, spectral resolution, etc.). We have validated the stability of the instrumental visibility at the level of 1 to 2% over half an hour and of the instrumental polarization for various declinations. Some examples of squared visibility and differential visibility are presented. Conclusions. The spectro-polarimeter VEGA has been installed and successfully tested on CHARA. It will permit stellar physics studies at unprecedented spectral and spatial resolutions.
The Changing Living Arrangements of Children, 1946–2001⋆

Widespread social changes over the last half century have been reflected in changes in family forms. These changes have resulted in increased family diversity which, in turn, is reflected in the more diverse living arrangements experienced by children as they grow up. This paper is the first to provide reliable national estimates of the extent to which the living arrangements of Australian children have changed. Using relationship and fertility histories from the nationally representative Household, Income and Labour Dynamics in Australia household panel survey (HILDA), the analysis describes the changing patterns of living arrangements of 12,441 children between 1946–2001. Its methodology allows the examination of the different living arrangements experienced by children during the first 15 years of life and avoids the static analysis that relies on point-in-time estimates. Furthermore, unlike analysis that relies on official birth and divorce statistics, the present analysis is able to identify family changes experienced by children as a result of parental separation. Thus, it takes into account transitions related to parental cohabitation as well as marriage.
Analyzing Gene Expression Profile in K562 Cells Exposed to Sodium Valproate Using Microarray Combined with the Connectivity Map Database

To explore the mechanism underlying antileukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed and validated. The differentially expressed genes identified were further used to query the connectivity map database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis and a change in gene expression profile were observed in valproate-exposed K562 cells. The significant enrichment analysis of gene ontology terms for the differentially expressed genes showed that these genes were involved in many important biological processes. Eight differentially expressed genes involved in apoptosis were verified by quantitative real-time PCR. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate was most similar to that of HDACi and PI3K inhibitors, suggesting that sodium valproate might exert antileukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, our data might provide clues to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment, and the connectivity map is a useful tool for exploring the molecular mechanism of drug action.
Personality, Interest, and Motivational Determinants of Maximal and Typical Performances on a Verbal Knowledge Task

The motivation constructs of Need for Cognition, Liking in Thinking, and Typical Intellectual Engagement, NEO Five-Factor Inventory factors, and RIASEC interests along with age were used to predict verbal tasks completed under timed (maximal performance) or untimed (typical performance) conditions. The results from a sample of 341 participants (245 female and 116 male), ranging in age from 18 to 71 years (M = 29.33, SD = 12.08), indicated that the men and women diverge in the relationships between their noncognitive domains and the verbal tasks. That is, women's verbal abilities are influenced by their age, and personality, interests, and motivations, whereas only personality and age contributed to verbal abilities in men. The results also displayed that the context in which a cognitive task is performed induced either maximal or typical efforts with different relationships with the predictor variables. The implications of the findings in relation to workplace training and development are discussed.
Authentic Work and Organizational Change: Longitudinal Evidence from a Merger

This article explores how a profound organizational change may impact employees' abilities to work in an authentic manner. Authentic work hinges on subjectively experienced alignments between one's work identity and the nature, purpose and practices of one's work. It is proposed that people thrive when engaged in authentic work. The article is founded on a longitudinal qualitative case study in a public sector organization going through a merger. The interview data indicate that an organizational transformation may create (mis)alignments between work and identity on two levels. The informants considered whether their emerging work corresponded to their core self-definitions at work and whether they were able to carry out their work in a manner they found meaningful. Authentic work and positive individual-level outcomes resulted from alignments between work and identity, interpreted as chances for self-continuity or self-enhancement, and from new work practices that made it possible to realize values and beliefs about work. Inauthenticity was experienced when the new job in the post-merger organization was experienced as more confined, wrongly focused, and when the competence demands misaligned with self-assessed competences. The article provides examples of how the informants aimed at realigning their identities and work by carrying out job crafting and identity work.
Social Identity Processes in Organizational Contexts

M.A. Hogg, D.J. Terry, Social Identity Theory and Organizational Processes. M.G. Pratt, Social Identity Dynamics in Modern Organizations: An Organizational Psychology/Organizational Behavior Perspective. B.E. Ashforth, S.A. Johnson, Which Hat to Wear? : The Relative Salience of Multiple Identities in Organizational Contexts. S. Brickson, M.B. Brewer, Identity Orientation and Intergroup Relations in Organizations. M. Hewstone, R. Martin, C. Hammer-Hewstone, R. Crisp, A. Voci, Majority-minority Relations in Organizations: Challenges and Opportunities. R. Moreland, J. Levine, J. McMinn, Self-categorization and Work Group Socialization. N. Ellemers, Social Identity, Commitment, and Work Behavior. C. Bartel, J. Dutton, Ambiguous Organizational Memberships: Constructing Organizational Identities in Interactions with Others. D. Abrams, G. Randsley de Moura, Organizational Identification: Psychological Anchorage and Turnover. T. Tyler, Cooperation in Organizations: A Social Identity Perspective. R.M. Kramer, Identity and Trust in Organizations: One Anatomy of a Productive but Problematic Relation. J.T. Jost, K.D. Elsbach, How Status and Power Differences Erode Personal and Social Identities at Work: A System Justification Critique of Organizational Applications of Social Identity Theory. M.A. Hogg, Social Identification, Group Prototypicality, and Emergent Leadership. S.A. Haslam, M.J. Platow, Your Wish is Our Command: The Role of Shared Social Identity in Translating a Leader's Vision into Follower's Action. D.J. Terry, Intergroup Relations and Organizational Mergers. D. van Knippenberg, E. van Leeuwen, Organizational Identity after a Merger: Sense of Continuity as the Key to Post-merger Identification. S. Gaertner, B. Bachman, J. Dovidio, B. Banker, Corporate Mergers and Stepfamily Marriages: Identity, Harmony, and Commitment.
Chinese and German teachers' conceptions of play and learning and children's play behaviour

Commonalities and distinctions in Hong Kong-Chinese and German kindergarten teachers' conceptions of play and learning were examined. Six video clips of play episodes reflecting common play behavior and themes were selected from observations made during free play in two kindergartens in Hong Kong and two in Germany. Ten Chinese and seven German teachers viewed clips of children in their own and the other culture in small groups, participated in a semi-structured group discussion, and completed questionnaires, respectively. Results indicated that teachers in the two contexts had different views on the role of play in curriculum, teacher intervention during children's play, and learning objectives in play. These differences may be a function of different ecological environments and preset learning objectives. Findings suggest that teachers' cultural beliefs about play and learning are translated into actions (play arrangements) which, in turn, influence children's play behavior.
Optimal rate allocation in successively structured Gaussian CEO problem

We consider the Chief Executive Officer (CEO) problem in which agents encode their observations without collaborating with each other and send through rate constrained noiseless channels to a fusion center (FC). We apply the successive coding strategy into this problem and determine the closed-form expressions for optimal rates in order to achieve the minimum distortion under a sum-rate constraint. We show that the optimal sum-rate distortion performance for the Gaussian CEO problem is achievable using the successive coding strategy which is inherently a low complexity approach of obtaining a prescribed distortion. We also determine the optimal rate allocation region for the successively structured Gaussian CEO problem.