Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: A preliminary report

DNA methylation changes could provide a mechanism for DNA plasticity and dynamism for short‐term adaptation, enabling a type of cell memory to register cellular history under different environmental conditions. Some environmental insults may also result in pathological methylation with corresponding alteration of gene expression patterns. Evidence from several studies has suggested that in schizophrenia and bipolar disorder, mRNA of the reelin gene (RELN), which encodes a protein necessary for neuronal migration, axonal branching, synaptogenesis, and cell signaling, is severely reduced in post‐mortem brains. Therefore, we investigated the methylation status of the RELN promoter region in schizophrenic patients and normal controls as a potential mechanism for down regulation of its expression. Ten post‐mortem frontal lobe brain samples from male schizophrenic patients and normal controls were obtained from the Harvard Brain Tissue Resources Center. DNA was extracted using a standard phenol–chloroform DNA extraction protocol. To evaluate differences between patients and controls, we applied methylation specific PCR (MSP) using primers localized to CpG islands flanking a potential cyclic AMP response element (CRE) and a stimulating protein‐1 (SP1) binding site located in the promoter region. For each sample, DNA extraction, bisulfite treatment, and MSP were independently repeated at least four times to accurately determine the methylation status of the target region. Forty‐three PCR trials were performed on the test and control samples. MSP analysis of the RELN promoter revealed an unmethylated signal in all reactions (43 of 43) using DNA from the frontal brain tissue, derived from either the schizophrenic patients or normal controls indicating that this region of the RELN promoter is predominantly unmethylated. However, we observed a distinct methylated signal in 73% of the trials (16 of 22) in schizophrenic patients compared with 24% (5 of 21) of controls. Thus, the hypermethylation of the CpG islands flanking a CRE and SP1 binding site observed at a significantly higher level (t = −5.07, P = 0.001) may provide a mechanism for the decreased RELN expression, frequently observed in post‐mortem brains of schizophrenic patients. We also found an inverse relationship between the level of DNA methylation using MSP analysis and the expression of the RELN gene using semi‐quantitative RT‐PCR. Despite the small sample size, these studies indicate that promoter hypermethylation of the RELN gene could be a significant contributor in effecting epigenetic alterations and provides a molecular basis for the RELN gene hypoactivity in schizophrenia. Further studies with a larger sample set would be required to validate these preliminary observations. © 2005 Wiley‐Liss, Inc.
Measuring and Modeling Intergenerational Links in Relation to Long‐Term Care

Longâterm care has profound intergenerational implications. It can be costly for those who need it and onerous for loved ones who provide it. We pinpoint three intergenerational aspects of longâterm care that require further research. One concerns the link between costs of private care and intergenerational wealth transfers. The second concerns the link between participation in care and the work and welfare of family providers. The third relates to intergenerational tensions that these and other lateâinâlife interactions create. We outline innovations in modeling and measurement that would improve understanding of intergenerational linkages and their implementation in appropriate panel data. (JEL D91, I13, J22)
Can Fiscal Budget-Neutral Reforms Stimulate Growth? Model-Based Results

This paper focuses on growth enhancing budget-neutral fiscal reforms, i.e. changes in the composition of government revenues and spending that stimulate GDP growth while keeping the ratio of the fiscal budget to GDP constant. To this aim, we present simulation results using a multi-country DSGE model with three large economic regions, the US, the euro area and the rest of the world. The model features constrained and unconstrained non-Ricardian households and a detailed government sector; its multi-country nature allows investigating cross-country spillovers. The paper focuses on the most growth-friendly budget-neutral fiscal measures: (i) an incomplete fiscal devaluation (ii) a rise in government investment compensated by a fall in government consumption and (iii) a rise in government investment compensated by a rise in consumption and labor taxes. Dampening or amplifying effects due to coordination across policies (monetary and fiscal) and across economic regions are also considered. Three main results stand out. First, an increase in government investment financed by rising less distortionary taxes appears to be an effective growth-friendly budget-neutral reform in the sense that it generates both short- and long-run GDP growth and improves fiscal sustainability. Second, benefits and costs of budget-neutral reforms are not equally distributed across agents, giving rise to a policy trade-off between growth and distributional consequences. Third, budget-neutral reforms do not have large cross-border trade spillovers; however, reforms coordinated across all countries in periods of accommodative monetary policy do have amplified domestic effects.
Allosteric Control of Cyclic di-GMP Signaling*

Cyclic di-guanosine monophosphate is a bacterial second messenger that has been implicated in biofilm formation, antibiotic resistance, and persistence of pathogenic bacteria in their animal host. Although the enzymes responsible for the regulation of cellular levels of c-di-GMP, diguanylate cyclases (DGC) and phosphodiesterases, have been identified recently, little information is available on the molecular mechanisms involved in controlling the activity of these key enzymes or on the specific interactions of c-di-GMP with effector proteins. By using a combination of genetic, biochemical, and modeling techniques we demonstrate that an allosteric binding site for c-di-GMP (I-site) is responsible for non-competitive product inhibition of DGCs. The I-site was mapped in both multi- and single domain DGC proteins and is fully contained within the GGDEF domain itself. In vivo selection experiments and kinetic analysis of the evolved I-site mutants led to the definition of an RXXD motif as the core c-di-GMP binding site. Based on these results and based on the observation that the I-site is conserved in a majority of known and potential DGC proteins, we propose that product inhibition of DGCs is of fundamental importance for c-di-GMP signaling and cellular homeostasis. The definition of the I-site binding pocket provides an entry point into unraveling the molecular mechanisms of ligand-protein interactions involved in c-di-GMP signaling and makes DGCs a valuable target for drug design to develop new strategies against biofilm-related diseases.
A Method for Image Registration by Maximization of Mutual Information

Registration is an important problem and a fundamental task in image processing technique. in the medical image processing fields, some techniques are proposed to find a geometrical transformation that relates the points of an image to their corresponding points of another image. In recent years, multimodality image registration techniques are proposed in the medical imaging field. Especially, CT and MR imaging of the head for diagnosis and surgical planning indicates that physicians and surgeons gain important information from these modalities, in radiotherapy planning manual registration techniques performed on MR image and CT images of the brain. Now-a-days, physicians segment the volumes of interest (VOIs) from each set of slices manually. However, manual segmentation of the object area may require several hours for analysis. Furthermore, MDCT images and MR images contain more than 100 slices. Therefore, manual segmentation and registration method cannot apply for clinical application in the head CT and MR images. Many automatic and semiautomatic image registration methods have been proposed. The main techniques of image registration are performed by the manual operation, using landmark and using voxel information, in this paper, we develop a new method for automatic registration of head images by computer which obtained CT and MR images employing maximization of mutual information. The mutual information registration criterion allows fully automated, highly robust registration of multimodal images. The primary objective of this study is to increase accuracy of the registration and reduce the processing time
Technoculture and democratization: noise, limits and opportunities concerning Labs

La cultura que surge del impacto computacional define un gran momento de cambio e innovación en el que el concepto de diseño alcanza unas dimensiones y consecuencias muy radicales. Aparecen nuevas identidades e instituciones. Una de ellas, el lab, ha hecho fortuna como descriptor difuso de entidades muy diferentes, y también como depositaria de exigencias democratizadoras ante los cambios actuales. Esta popularidad reclama una cierta clarificación, pues el mismo concepto de “laboratorio” ha estallado bajo el impacto de lo digital. Contrastamos estos nuevos labs con los antiguos considerándolos desde los parámetros de la práctica tecnológica y sus formas de innovación e investigación propias de la tecnocultura. Esto nos permite identificar problemas y carencias de las nuevas organizaciones en lo que respecta a la democratización de la tecnocultura. También nos ayuda a detectar nuevas oportunidades de investigación en el cruce entre tecnología, diseño y ciencias sociales.
Resource changes: exogenous or endogenous, gradual or abrupt. Experimental evidence

ABSTRACT The paper reports a laboratory experiment in which groups of participants managed a Common-Pool Resource (CPR). The goal was to observe if different types of resource change, whether exogenous or endogenous, and gradual or sudden, would lead to different behaviour, and if the participants would adapt easily to any one of these changes. The experiment used a time continuous, dynamic tool. Endogenous resource changes, when compared with exogenous changes, led to higher cooperation, and a better management of the resource, thus reducing the risk of extinction through overharvesting. Abrupt changes appear to induce users to modify their behaviour according to what happens to the resource, but gradual changes do not seem to lead to behavioural change. In line with previous research, our results suggest that, when the users are aware of the threat of potential disasters, they can adapt their behaviour and move toward a solution which can avoid the tragedy of the commons.
Social media based linking approach for finding the effectiveness of the social issues

This paper introduces sentiment analysis based technique to determining the effectiveness of the post related to the various social issues through people feedback their suggestions and comments corresponding to that social issue posted on social media. The main contribution towards this paper is (i) to analyze and interpret public opinion and sentiments related to the post posted on the social media (ii) to calculate the effectiveness of that post corresponding to that social issue. For this we have used Sentiword net to classify the words as positive or negative and used the concept of Naive Bayes to classify the feedback into positive and negative classes using probability based function and support vector machine to create decision boundary from which we can determine the effectiveness of the post.
Folding DNA into Twisted and Curved Nanoscale Shapes

Stressful Self-Assembly One way to control shape during the assembly of an object is to design in stresses that cause a planned amount of deformation. Dietz et al. (p. 725; see the Perspective by Liu and Yan) designed DNA helix bundles, arranged in honeycomb lattices, in which some of the helices have insertions or deletions relative to the other helices in the bundles. The stresses help the bundles assemble into objects on the scale of tens of nanometers. Both the direction and degree of bending could be controlled, and curvatures as tight as 6 nanometers achieved. Complex shapes, such as square-toothed gears, could be created by combining multiple curved elements. Site-directed insertions and deletions of base pairs direct twist and curvature in crystal-like DNA arrays. We demonstrate the ability to engineer complex shapes that twist and curve at the nanoscale from DNA. Through programmable self-assembly, strands of DNA are directed to form a custom-shaped bundle of tightly cross-linked double helices, arrayed in parallel to their helical axes. Targeted insertions and deletions of base pairs cause the DNA bundles to develop twist of either handedness or to curve. The degree of curvature could be quantitatively controlled, and a radius of curvature as tight as 6 nanometers was achieved. We also combined multiple curved elements to build several different types of intricate nanostructures, such as a wireframe beach ball or square-toothed gears.
Re-conceptualising learning-centred (instructional) leadership: an obsolete concept in need of renovation

For more than thirty years, ‘instructional leadership’ has been at the forefront of research and practice in school effectiveness and improvement. Governments, employers, universities and professional developers, all see it as a mainstay of raising school and student performance. Wave-after-wave of educational policy reforms during this period have changed school environments, widening and deepening the (instructional) leadership roles and functions of principals and other school leaders. Terminology has changed – while Americans still use ‘instructional leadership’, others prefer ‘learning-centred’ and ‘leadership-for -learning’, disputing whether they encompass the same or different meanings. Yet curiously, the concept itself – as defined and measured by academic researchers and scholars - has changed relatively little since Hallinger and Murphy’s first seminal contribution in 1985. This paper argues the case for wholesale renovation of the concept if it is to maintain relevance going forward. The case is supported by important and powerful trends in policy and practice.
Review of Financial Crises, Liquidity, and the International Monetary System by Jean Tirole

Jean Tirole is a distinguished economist, well known for his contributions to game theory, industrial organization, and corporate finance. Although Tirole wrote a much cited paper on price bubbles in intertemporal general equilibrium models early in his career, he has not been known for his work on open economy macroeconomics. In this book, Tirole takes on the topic of the international financial crises in developing countries that have occurred since the 1994-1995 Mexican crisis from the point of view of an outsider: he studies this topic using the tools of contract theory, in particular, variations of the principal-agent model. Reviewing the large and growing literature on international financial crises, Tirole concludes that most of it has focused on the symptoms, rather than on the underlying causes, of the crises. He asks, Why does capital account liberalization in developing counties sometimes lead to what are perceived as inefficient market outcomes? What determines a country’s access to attractive levels and forms of financing? What is the role of the international financial institutions, such as the International Monetary Fund (IMF), in regulating international capital flows? The book proposes a framework for analyzing international financial crises using the sorts of tools used in the modern theory of corporate finance. Tirole identifies two sources of market failures that lead to an undersupply of funds in international context: the dual agency problem and the common agency problem. The market failures result from externalities that are not internalized in the absence of contracting with the government. Tirole sketches out a potential role for the IMF in helping borrowers and lenders internalize these externalities and thereby ensure an efficient allocation of capital across countries. The dual agency problem arises when the actions of two agents affect the payoff of one principal. In the context of capital account crises, Tirole observes that, while a foreign lender (the principal) can contract with a private borrower (one of the agents), the lender cannot contract with the borrower’s government (the other agent). The government’s actions affect the return on foreign investment, however, through such instruments as taxes and exchange rates. There is a time-consistency problem: ex ante, the government would like to commit to policies that increase expected return on foreign investment, but, ex post, once investment is sunk, the government has no incentives to
The reliability of long – term energy forecasts

The paper demonstrates that the possibilities of producing reliable long-term energy forecast are limited. Global economic growth is so dynamic that the changes resulting from scientific and technological progress, which we experience, do not allow for the identification of goals over longer time intervals. For this reason, forecasting up to 2035, 2040, 2060 is devoid of its fundamental value, which is the reliability of results obtained. Are predictions to be conservative (this applies to richer countries) or are they to produce a paradigm shift by, for example, strongly imposing the requirement of increasing energy security, which is important for our country? In light of the broadness of the issues, this paper is limited to considerations relating to forecasting the primary energy demand. Detailed examples are presented for the Polish energy system.
Molecular dynamics of zinc-finger ubiquitin binding domains: a comparative study of histone deacetylase 6 and ubiquitin-specific protease 5

HDAC6 is a unique cytoplasmic histone deacetylase characterized by two deacetylase domains, and by a zinc-finger ubiquitin binding domain (ZnF-UBP) able to recognize ubiquitin (Ub). The latter has recently been demonstrated to be involved in the progression of neurodegenerative diseases and in mediating infection by the influenza A virus. Nowadays, understanding the dynamic and energetic features of HDAC6 ZnF-UBP-Ub recognition is considered as a crucial step for the conception of HDAC6 potential modulators. In this study, the atomic, solvent-related, and thermodynamic features behind HDAC6 ZnF-UBP-Ub recognition have been analyzed through molecular dynamics simulations. The behavior was then compared to the prototypical ZnF-UBP from ubiquitin-specific protease 5 (USP5) in order to spot relevant differences useful for selective drug design. Principal component analysis highlighted flapping motions of the L2A loop which were lowered down upon Ub binding in both systems. While polar and nonpolar interactions involving Ub G75 and G76 residues were also common features stabilizing both complexes, salt bridges showed a different pattern, more significant in HDAC6 ZnF-UBP-Ub, whose energetic contribution in USP5 ZnF-UBP-Ub was compensated by the presence of a more stable bridging water molecule. Whereas molecular mechanics/Poisson–Boltzmann surface area (MM-PBSA) free energies of binding were comparable for both systems, in agreement with experiments, computational alanine scanning and free energy decomposition data revealed that HDAC6 E1141 and D1178 are potential hotspots for the design of selective HDAC6 modulators.
Mathematical Models of Ovarian Cancer Incidence

Background: Pike has proposed “protected time” as one summary method for modeling reproductive risk factors in relation to ovarian cancer incidence. We evaluate this and other approaches to summarizing risk for ovarian cancer. Methods: We identified 472 incident cases of ovarian cancer during 2,298,068 person-years of follow-up of 24- to 55-year-old premenopausal women at cohort inception. Reproductive exposures, use of oral contraceptives, and history of tubal ligation were evaluated. Results: Age at menopause is directly related to cumulative risk of ovarian cancer up to age 70 years (age 55 vs. age 45, risk increase = 62%; 95% confidence interval = 36 to 96%) and age at menarche is inversely related to risk (age 15 vs. 11, risk reduction = 31%; 27–34%). Use of oral contraceptives for 5 years before age 30 decreases risk of ovarian cancer to age 70 by 37% (32 to 41%). Tubal ligation reduces risk up to age 70 by 21% (−2 to 38%). Parity reduces risk, independent of age at first birth and age at last birth. A model summarizing years of ovulation offers a fit comparable to a more complex modeling of reproductive variables. The model fit is good, with a concordance statistic of 0.60 (0.57 to 0.62) indicating reasonable ability to differentiate those who will develop ovarian cancer from those who will remain disease free. Conclusion: This model may be applied in the identification of women at high risk for ovarian cancer, for example, in selecting candidates for prevention trials.
Salient Point Tracking for Key Frames Selection in Outdoor Image Sequences

Key frames are of great importance in applications where it is necessary to reduce information redundancy in the images, estimate a moving camera's pose efficiently, or make precise 3D reconstructions. Realtime key frame selection is commonly done by tracking many salient points until a certain percentage is no longer visible. The Fundamental-based tracker is an algorithm that maintains consistent correspondences through successive frames using the Fundamental matrix and the Epipolar geometry. We present an algorithm for tracking hundreds of salient points in sequences of monocular images of exterior urban and aquatic scenes. We extend the Fundamental- based tracker to discover points that are not extracted by the local feature detector because these points are below a threshold of detection. We employ the information of the scene geometry, the image appearance, and the apparent motion dynamics to find these points. This proposal allows maintaining many stable tracks for a longer time. We carry out an experimental evaluation on three very different image sequences captured by a single camera mounted on wheeled and underwater vehicles. Our algorithm shows a reliable tracking performance compared with the Pyramidal Lucas-Kanade tracker, at processing rates of 4 to 9 frames per second on a laptop.
Mesomelic dwarfism in pseudoachondroplasia

Pseudoachondroplasia (PSACH) is associated with mutations in the cartilage oligomeric matrix protein (COMP) gene and the clinical characteristics include short stature, deformities of the extremities involving the epiphyses and metaphyses, early onset arthritis, and ligament laxity. PSACH has been considered a rhizomelic form of dwarfism. So far no previous report has described mesomelic shortening of the limbs in PSACH. We reviewed nine patients with a diagnosis of PSACH based on clinical and radiographic examination and mutation analysis of the COMP gene. The mean height in the adults was 116 cm. All patients showed mesomelic dwarfism. The average ratios of radial length to humeral length and tibial length to femoral length were 0.62 and 0.63, respectively. The tibia and the radius showed more severe bony deformity than the femur and humerus. The degree of short stature was related to the site of the mutation in the COMP gene, but there was no correlation between bony deformity and height or gene mutation.