Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological plasticity related to zonation affects hsp70 expression in the reef-building coral Pocillopora verrucosa

This study investigates for the first time the transcriptional regulation of a stress-inducible 70-kDa heat shock protein (hsp70) in the scleractinian coral Pocillopora verrucosa sampled at three locations and two depths (3 m and 12 m) in Bangka Island waters (North Sulawesi, Indonesia). Percentage of coral cover indicated reduced habitat suitability with depth and at the Tanjung Husi (TA) site, which also displayed relatively higher seawater temperatures. Expression of the P. verrucosa hsp70 transcript evaluated under field conditions followed a depth-related profile, with relatively higher expression levels in 3-m collected nubbins compared to the 12-m ones. Expression levels of metabolism-related transcripts ATP synthase and NADH dehydrogenase indicated metabolic activation of nubbins to cope with habitat conditions of the TA site at 3 m. After a 14-day acclimatization to common and fixed temperature conditions in the laboratory, corals were subjected for 7 days to an altered thermal regime, where temperature was elevated at 31°C during the light phase and returned to 28°C during the dark phase. Nubbins collected at 12 m were relatively more sensitive to thermal stress, as they significantly over-expressed the selected transcripts. Corals collected at 3 m appeared more resilient, as they showed unaffected mRNA expressions. The results indicated that local habitat conditions may influence transcription of stress-related genes in P. verrucosa. Corals exhibiting higher basal hsp70 levels may display enhanced tolerance towards environmental stressors.
Cyclin D Expression Is Controlled Post-transcriptionally via a Phosphatidylinositol 3-Kinase/Akt-dependent Pathway*

Cyclin D expression is regulated by growth factors and is necessary for the induction of mitogenesis. Herbimycin A, a drug that binds to Hsp90, induces the destruction of tyrosine kinases and causes the down-regulation of cyclin D and an Rb-dependent growth arrest in the G1phase of the cell cycle. We find that the induction of D-cyclin expression by serum and its repression by herbimycin A are regulated at the level of mRNA translation. Induction of cyclin D by serum occurs prior to the induction of its mRNA and does not require transcription. Herbimycin A repression is characterized by a decrease in the synthetic rate of D-cyclins prior to changes in mRNA expression and in the absence of changes in the half-life of the protein. This effect on D-cyclin translation is mediated via a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. PI 3-kinase inhibitors such as wortmannin and LY294002, and rapamycin, an inhibitor of FRAP/TOR, cause a decline in the level of D-cyclins, whereas inhibitors of mitogen-activated protein kinase kinase and farnesyltransferase do not. Cells expressing the activated, myristoylated form of Akt kinase, a target of PI 3-kinase, are refractory to the effects of herbimycin A or serum starvation on D-cyclin expression. These data suggest that serum induction of cyclin D expression results from enhanced translation of its mRNA and that this results from activation of a pathway that is dependent upon PI 3-kinase and Akt kinase.
MRI techniques for prediction of local tumor progression after high-intensity focused ultrasonic ablation of prostate cancer.

OBJECTIVE The purpose of this study was to evaluate the diagnostic performance of dynamic contrast-enhanced MRI (DCE-MRI) and of T2-weighted MRI with diffusion-weighted imaging (DWI) for predicting local tumor progression after high-intensity focused ultrasonic ablation of localized prostate cancer. MATERIALS AND METHODS Twenty-seven patients who had increased levels of prostate-specific antigen after high-intensity focused ultrasonic ablation underwent MRI and endorectal biopsy. The MR images and biopsy results were correlated for six prostate sectors. Residual or recurrent prostate cancer after treatment was defined as local tumor progression if the biopsy results showed cancer foci. Two readers blinded to the clinical findings and biopsy results used a 5-point scale to independently assess DCE-MR images and T2-weighted and diffusion-weighted MR images. The results were compared by use of the McNemar test with Bonferroni correction, generalized estimating equations, and receiver operating characteristic analysis. RESULTS After high-intensity focused ultrasonic ablation, local tumor progression was pathologically detected in 54 (33%) of 162 sectors in 18 patients. The sensitivities of DCE-MRI and T2-weighted MRI with DWI were 80% and 63% for reader 1 (p = 0.004) and 87% and 70% for reader 2 (p = 0.004). The specificities of DCE-MRI and T2-weighted MRI with DWI were 68% and 78% for reader 1 (p = 0.002) and 63% and 74% for reader 2 (p < 0.001). The accuracy rates of DCE-MRI and T2-weighted MRI with DWI were 72% and 73% for reader 1 (p > 0.05) and 71% and 73% for reader 2 (p > 0.05). The areas under the receiver operating characteristic curve for DCE-MRI and T2-weighted MRI with DWI were 0.77 and 0.77 for reader 1 and 0.85 and 0.81 for reader 2. CONCLUSION For prediction of local tumor progression of prostate cancer after high-intensity focused ultrasonic ablation, DCE-MRI was more sensitive than T2-weighted MRI with DWI, but T2-weighted MRI with DWI was more specific than DCE-MRI.
Cultivating the good of school leadership purpose, coherence and excellence in practice

The primary motivation for this study has been to give consideration to a model of school leadership, which is based on the notion of ‘practice’ in Alasdair MacIntyre’s sense of that term. The intention is to provide school leadership with a language closer to what is known about the nature and activity of the school, the actual complexity of the school leadership situation and one that would give a much needed sense of coherence to the role and relationship expectations than currently exists. Given the moral context of schools, the study also contends that what is further required of such an account is that it is ethical in its substance, with questions of value and the good to the fore. Arising from these considerations, the study directs itself towards the philosophy of Alasdair MacIntyre, in particular his account of practices, with a view to crafting a lens that could inform a possible new language for school leadership. MacIntyre’s notion of practice connects well with education in a broader moral context because it emphasises the importance of ethically rich actions and notions of care and co-operation. The study has taken account of the extensive body of literature both internationally and in the Irish context which has looked at theoretical perspectives as well as the lives and work of school leaders on the ground. Whilst there have been significant developments in the field of school leadership research, a number of challenges exist. These are primarily concerned with issues of competing purposes, a general lack of coherence with regard to practice, role and relationship expectations, as well as conflicting accounts of what makes for good leadership in a school context. Drawing on MacIntyre’s theory of internal goods, the study has sought to consider how a more appropriate framework for the cultivation of the good of school leadership can be arrived at through addressing issues of purpose, coherence and excellence in practice.
Metastable regulation of type 1 piliation in Escherichia coli and isolation and characterization of a phenotypically stable mutant

Type 1 piliation in Escherichia coli exhibits phase variation due to the inversion of a small, ca. 300-base-pair, element that regulates pilA (fimA), the gene that encodes the structural subunit of pili (Abraham et al., Proc. Natl. Acad. Sci. USA 82:5724-5727, 1985). We have used the inversion as an assay to characterize a stably piliated mutant. The mutant strain did not exhibit the pilA ON and pilA OFF colonial variants characteristic of the wild type; rather, every clone produced a level of pilA expression intermediate between ON and OFF wild-type populations. The mutant phenotype was conferred by a lesion at a previously undescribed locus between hemA and trpA, which we have termed pilG. Examination of the pilA promoter region in four pilG mutant populations indicated that the phenotypic stability conferred by the pilG mutation was not due to an inability to carry out the inversion. Rather, all pilG mutant populations consisted of approximately equal mixtures of ON and OFF individuals. We suggest that pilG mutants may undergo such rapid switching of the pilA promoter that populations exhibit an intermediate level of pilA expression and phenotypic stability.
Efficacy of a slow‐release formulation of lanreotide (Autogel® 120 mg) in patients with acromegaly previously treated with octreotide long acting release (LAR): an open, multicentre longitudinal study

Objective Lanreotide Autogel® 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a high‐dose, sustained‐release aqueous gel formulation, supplied in a prefilled syringe and given by deep subcutaneous injection. The aim of this study was to compare efficacy and tolerability of ATG120 given every 4–8 weeks with those of octreotide LAR (o‐LAR) given every 4 weeks.
Charles A. Dice Center for Research in Financial Economics Government Debt and the Returns to Innovation

Elevated levels of government debt raise concerns about their effects on long-term growth prospects. Using the cross section of US stock returns, we show that (i) high-R&D firms are more exposed to government debt and pay higher expected returns than low-R&D firms, and (ii) higher levels of the debt-to-GDP ratio predict higher risk premiums for high-R&D firms. Furthermore, rises in the cost of capital for innovation-intensive firms predict declines in subsequent productivity and economic growth. We propose a production-based asset pricing model with endogenous innovation and fiscal policy shocks that can rationalize key aspects of the empirical evidence. Our study highlights a novel and distinct risk channel shaping the link between government debt and future growth. JEL classification: E62, H32, O33
Differential interaction of synthetic peptides from the carboxyl‐terminal regulatory domain of tubulin with microtubule‐associated proteins.

In previous studies we have demonstrated that a 4‐kd tubulin fragment, including amino acid residues from Phe418 to Glu450 in alpha‐subunit and Phe408‐Ala445 of the beta‐sequence, plays a major role in controlling tubulin interactions leading to microtubule assembly. The 4‐kd carboxyl‐terminal domain also constitutes an essential domain for the interaction of microtubule‐associated proteins (MAPs). Removal of the 4‐kd fragment facilitates tubulin self‐association and renders the assembly MAP‐independent. In order to define the substructure of the tubulin domain for MAP interaction, we have examined the binding of 3H‐acetylated C‐terminal peptides to MAP‐2 and tau. Two synthetic peptides from the low‐homology region within the 4‐kd domain alpha (430‐441) and beta (422‐434) and the peptide, alpha (401‐410) of the high‐homology region adjacent to the 4‐kd domain, were analyzed with respect to MAP interaction. The binding data showed a relatively strong interaction of MAP‐2 with the beta (422‐434) peptide and a weaker interaction of both MAPs components with alpha (430‐441) tubulin peptide as analyzed by Airfuge ultracentrifugation and zone filtration chromatography. The homologous alpha (401‐410) peptide did not bind to either MAP‐2 or tau. Equilibrium dialysis experiments showed a co‐operative binding of beta (422‐434) peptide to multiple sites in tau. The alpha (430‐441) peptide exhibited a stronger interaction for tau as compared with MAP‐2. (ABSTRACT TRUNCATED AT 250 WORDS)
Asset Price Bubbles and Technological Innovation

We introduce borrowing constraints into a two‐sector Schumpeterian growth model and examine the impact of asset price bubbles on innovation. In this environment, rational bubbles arise when the intermediate good producing R&D sector is faced with adverse productivity shocks. Importantly, these bubbles help alleviate credit constraints and facilitate innovation in the stagnant economy. On the policy front, we make a case for debt financed credit to the R&D sector. Further, we establish that a constant credit growth rule (akin to the Friedman rule) outperforms the often prescribed counter‐cyclical “lean against the wind” credit policy. (JEL E32, E44, O40)
Cerebral asymmetry for mental rotation: effects of response hand, handedness and gender

We assessed lateralization of brain function during mental rotation, measuring the scalp distribution of a 400–600 ms latency event-related potential (ERP) with 128 recording electrodes. Twenty-four subjects, consisting of equal numbers of dextral and sinistral males and females, performed a mental rotation task under two response conditions (dominant vs non-dominant hand). For males, ERPs showed a right parietal bias regardless of response hand. For females, the parietal ERPs were slightly left-lateralized when making dominant hand responses, but strongly right-lateralized when making non-dominant hand responses. These results support the notion that visuo-spatial processing is more bilaterally organized in females. However, left hemisphere resources may be allocated to response preparation when using the non-dominant hand, forcing visuo-spatial processing to the right hemisphere.
Can university senior managers take lessons from sports coaching?

ABSTRACT Athletes qualify as ‘elite’ in club, university and national arenas, in terms of their relatively high level of ability and sporting quality. Academic staff in universities have been appointed to their posts based on their intellectual and practical research and teaching abilities/ qualities. Athletes are managed by professional sports coaches and academics are led by senior colleagues appointed for their research, teaching and academic management experience. If elite athletes and academics are compared, distinct similarities are evident. Management and Leadership studies often take examples from sport when considering qualities and lessons for individual or team success. This article considers the benefits or otherwise resulting from sports coach management in terms of the motivational climate, approach, interactions, and technique for performance improvement. It compares these behaviours and outcomes to published academics’ views and the lessons revealed in HE and general business leadership studies and perspectives from a cross-section of literature.
Density Forecast Evaluations via a Simulation-Based Dynamic Probability Integral Transformation*

This paper presents simulation-based density forecast evaluation methods using particle filters. The simulation-based dynamic probability integral transformation or log-likelihood evaluation method is combined with the existing density forecast evaluation methods. This methodology is applicable to various density forecast models, such as log stochastic volatility models and affine jump diffusion (AJD) models, for which the probability integral transform or likelihood computation is difficult due to the presence of latent stochastic volatilities. This methodology is applied to the daily S&P 500 stock index. The empirical results show that the AJD models with jumps perform the best for out-of-sample evaluations.
The promise of heat shock protein inhibitors in the treatment of castration resistant prostate cancer

Purpose of review To present the recent advances in novel agents that target heat shock proteins (Hsps) to treat or delay the development of castration resistant prostate cancer (CRPC). Recent findings Multiple preclinical studies have shown that silencing Hsp27, Hsp90, or clusterin sensitizes prostate cancer cells to modern chemotherapy and radiation treatments; and overexpression of these chaperones confers resistance to these therapies. Antisense oligonucleotides targeting Hsp27 and clusterin have shown good biological activity in human phase II trials and phase III studies are ongoing. Despite promising preclinical efficacy, a number of phase I/II human trials with various Hsp90 inhibitors have been disappointing with negligible anticancer activity and dose-limiting toxicity profiles. Newer Hsp90 inhibitors with better toxicity profiles, and inhibitors that target Hsp90 cofactors, such as FKBP52, are currently being investigated in human studies. Summary Many Hsp chaperone client proteins are key components of alternative growth factor pathways upregulated in CRPC and are involved in key resistance pathways to current chemotherapy and radiotherapy regimes. New treatments that inhibit Hsps are attractive anticancer strategies as they have the ability to simultaneously target multiple pathways involved in CRPC.
In Vivo Effects of Naproxen, Salicylic Acid, and Valproic Acid on the Pharmacokinetics of Trichloroethylene and Metabolites in Rats

It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.
CT Scan Study of Atlantoaxial Rotatory Mobility in Asymptomatic Adult Subjects: A Basis for Better Understanding C1–C2 Rotatory Fixation and Subluxation

Study Design. Normal rotation was evaluated in a group of 40 asymptomatic adults. Objective. To determine the normal rotational limits of C1–C2 in adults and define when a rotatory fixation occurs in the limits of normality or in subluxation. The term subluxation should be used only when C1–C2 is rotated beyond normal limits. Summary of Background Data. Concepts about rotatory fixation were established by accepting that it may occur within the limits of normal range of motion. Although nowadays CT is the current image method used to evaluate any case of torticollis, no study has been performed in adult population on what really normal rotation look like in CT scans. Methods. The study included the measurement of the rotational movement of the neck and a CT scan study of the articular processes of C1–C2 in maximal, left and right, active rotation. A superposition of 6 consecutive slices was carried out, obtaining a linear contour of the axial view of C1–C2. Rotation angle and contact surface loss were measured. Results. The average neck rotation angle was 79° (range: 74° to 81°). The superposition of the images taken in every rotational direction showed a wide contact loss between the correspondent C1–C2 articular surfaces (42.4%–85.7%; average: 70%). The report of these images, carried out by 3 independent radiologists, concluded that there was a rotatory subluxation in all these cases. Conclusion. Our results coincide with our previous published ones conducted in children, and lead us to conclude that a CT scan showing wide—but incomplete—rotational facet displacement is not sufficient to define subluxation. We perceive that there is a risk of overdiagnosis and overtreatment (C1–C2 arthrodesis) when evaluating upper cervical spine rotational problems. The concept of both rotatory fixation and subluxation should be revised, and quantifying the rotational angle and contact surface loss between C1–C2 can be very useful.
Exploratory factor analysis of obsessive-compulsive patients and association with 5-HTTLPR polymorphism.

The determination of a genetic basis for obsessive-compulsive disorder (OCD) depends on how phenotypic boundaries are defined. Although a hypothesis for serotonin dysfunction in OCD has been advanced, no genes specifically responsible for serotonin regulation have as yet been definitively related to the etiology of OCD. The phenotypic variability of OCD could be at the basis of the failure of molecular biology investigations to find any genes involved in the liability to the disorder. Obsessive and compulsive contents can aggregate in OCD patients differently; multifactorial description may therefore be able to account for OCD phenotypic variance. Using principal component analysis, we derived five factors from 13 main contents of the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and considered them as quantitative phenotypes to evaluate their possible association with an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR). A trend toward positive association between the fifth factor, including counting and repeating rituals, and 5-HTTLPR was found. However, only considering the subgroup of patients with tic codiagnosis, we found a significantly higher score for the fifth factor for patients with L/L genotype with respect to L/S and S/S genotypes.
IL-18 Acts in Synergy with IL-7 To Promote Ex Vivo Expansion of T Lymphoid Progenitor Cells

Although IL-18 has not previously been shown to promote T lymphopoiesis, results obtained via a novel data mining algorithm (global microarray meta-analysis) led us to explore a predicted role for this cytokine in T cell development. IL-18 is a member of the IL-1 cytokine family that has been extensively characterized as a mediator of inflammatory immune responses. To assess a potential role for IL-18 in T cell development, we sort-purified mouse bone marrow–derived common lymphoid progenitor cells, early thymic progenitors (ETPs), and double-negative 2 thymocytes and cultured these populations on OP9–Delta-like 4 stromal layers in the presence or absence of IL-18 and/or IL-7. After 1 wk of culture, IL-18 promoted proliferation and accelerated differentiation of ETPs to the double-negative 3 stage, similar in efficiency to IL-7. IL-18 showed synergy with IL-7 and enhanced proliferation of both the thymus-derived progenitor cells and the bone marrow–derived common lymphoid progenitor cells. The synergistic effect on the ETP population was further characterized and found to correlate with increased surface expression of c-Kit and IL-7 receptors on the IL-18–treated cells. In summary, we successfully validated the global microarray meta-analysis prediction that IL-18 affects T lymphopoiesis and demonstrated that IL-18 can positively impact bone marrow lymphopoiesis and T cell development, presumably via interaction with the c-Kit and IL-7 signaling axis.