Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-distance regulation of Add2 pre-mRNA3′end processing

Accurate 3′end processing depends on the correct recognition of polyadenylation regulatory elements by specific protein complexes. In addition to the well-known hexanucleotide motif and downstream sequence element (DSE), less-defined auxiliary elements are usually found to modulate cleavage and polyadenylation. They are generally located in close proximity to the core polyadenylation elements but, in most of the cases, the molecular mechanisms involved are not well defined. We concentrated our studies on the regulation of the mouse β adducin (Add2) pre-mRNA cleavage and polyadenylation. It contains two proximal erythroid-specific (PAS1 and PAS2-3) and one distal brain-specific (PAS4) polyadenylation sites along the 3′UTR. Using an in vivo approach based in the transfection of minigenes containing the Add2 polyadenylation signals, we previously identified the core regulatory elements responsible for PAS4 activity. Here, we have identified two novel non-canonical cis-acting elements regulating 3′end processing at PAS4, which show long-distance activities. The first of these elements, which spans for 257 nucleotides and is located at more than 5 kb upstream the PAS4, was essential to enable processing at the Add2 PAS4. The second element, located at about 4.5 kb upstream of the PAS4, reduces PAS4 processing. Both elements display long-distance activities and, to our knowledge, long-distance upstream polyadenylation regulatory elements have not been previously described in non-viral eukaryotic transcripts. These results highlight the complexity of the regulatory mechanisms directing Add2 pre-mRNA 3′end processing, and suggests that pre-mRNA 3′ end processing of other genes may also be unexpectedly regulated by non-canonical auxiliary elements.
Trends in stroke incidence and acute case fatality in a Japanese rural area : the Oyabe study.

BACKGROUND AND PURPOSE Stroke mortality in Japan has significantly declined during recent decades. To determine the cause of this decrease, we studied the trends in stroke incidence and case fatality within 28 days after stroke in a rural area in Japan. METHODS We used a population-based registry during 1977-1991 in Oyabe, a rural area in the central part of Japan. The average population aged 25 years and older numbered 32 859 persons. Changes in age-standardized stroke incidence rate were calculated and compared between the 3 periods 1977-1981, 1982-1986, and 1987-1991. The 28-day case fatality rate was evaluated and also compared between the 3 periods by onset year. RESULTS The total number of strokes was 2068. The age-standardized incidence rate of all strokes decreased during the 15-year period, from 605 to 417 per 100 000 in men and from 476 to 329 per 100 000 in women. A marked decline was found during 1977-1986 but was not apparent during 1987-1991. Moreover, there was an increase in the group aged 75 years and older. The 28-day case fatality rates for all strokes improved from 18.0% to 14.2% in men and from 26.8% to 19.1% in women during the observation period. CONCLUSIONS These data indicate that declines in the stroke incidence and the 28- day case fatality have been associated with a marked decrease in stroke-related mortality in Japan.
Financial Economics and Actuarial Practice Financial Economics and Actuarial Practice

Starting in the U.K. and continuing through the U.S. and Canadian actuarial professions, proponents of financial economics have been forcefully promoting a review of traditional actuarial practices and training. In particular, the financial theories first proposed by Modigliani and Miller and subsequently developed by others have been used to highlight serious weaknesses in typical actuarial thinking. In summary, it is claimed that much actuarial advice wrongly specifies value, that guidelines and standards need radical revision and that traditional actuarial intuition suffers in comparison to newer modes of thought adopted by other professions. This paper examines concepts from both financial economics and actuarial science as applied to defined benefit schemes using a simple discounted cash-flow framework as a reference point. The general finding is that many standard modes of actuarial thought are, in fact, indefensible when examined with the tools and techniques of financial economics. The call for revision of actuarial training and practices is credible and necessary. However, the paper also touches on areas where a heavy-handed application of finance theory could be misguided due to limitations in the simple financial economic models presented. It concludes that financial economics should be carefully integrated into actuarial thought, rather than appended to existing actuarial theory or inserted as a wholesale replacement.
Accountability Policy at the Street Level in Kentucky: Teachers and Administrators Debate the Fairness of Continuous Improvement versus Relative Standing.

While scholars of educational accountability policy will not be surprised at the power of local implementers in modifying accountability efforts, Kentucky's street-level debate splits two constituencies in defining a fair system. Advocates for the education of all children including the poor and minorities support the continuous improvement model, while elite advocates support recognition of relative standing of schools. This paper includes data from teachers and administrators in four schools identified as eligible for state assistance under Kentucky's testing and accountability system. Of particular interest are the perceptions of accountability held by teachers and administrators in one school that had received rewards over two biennial periods prior to the current accountability designation. Across all four schools, teachers found the concept of continuous improvement unrealistic. Yet, many teachers accepted the apparent inevitability of emerging accountability requirements on their profession. (Contains 61 references.) (Author/SLD) Reproductions supplied by EDRS are the best that can be made from the ori inal document. 1 PERMISSION TO REPRODUCE AND DISSEMINATE THIS MATERIAL HAS BEEN GRANTED BY TO THE EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC) U.S. DEPARTMENT OF EDUCATION Office of Educational Research and Improvement EDU ATIONAL RESOURCES INFORMATION CENTER (ERIC) This document has been reproduced as received from the person or organization originating it. 0 Minor changes have been made to improve reproduction quality. o Points of view or opinions stated in this document do not necessarily represent official OERI position or policy. Accountability Policy at the Street Level in Kentucky: Teachers and Administrators Debate the Fairness of Continuous Improvement versus Relative Standing By Jane Clark Lindle, Ph.D. Associate Professor & Codirector University of Kentucky UK/U of L Joint Center for the Study of Educational Policy 101 Taylor Education Building Lexington, KY 40506-0001 (859) 257-8921/6734 FAX: (859) 257-1015 E-mail: jcLind00@pop.uky. edu www.uky. edu/Education/IER/joint.htm A paper prepared for the annual meeting of the American Educational Research Association (AERA), April 2000, New Orleans. Please do not quote or cite without permission of the author.
Revisiting the Cognitive Model of Depression: The Role of Expectations

The cognitive model of depression was highly stimulating for a better understanding and development of treatment for depression. However, the concept of “cognition” is rather broad and unspecific, and we suggest to focus on the cognitive subset of expectation. We conducted a narrative review on the role of expectations, and present an expectation-focused model of explaining why depression tends to persist despite the occurrence of positive events. Several results from basic neuroscience to effects in clinical interventions indicate that expectations play a special role not only for the understanding of the development of mental disorders and the effects of treatment approaches, but especially for an improved understanding of the persistence of mental disorders. If expectations are a major mechanism of depression, the treatment of depression must maximize the violation of dysfunctional expectations. We also introduce the concept of immunization that describes any cognitive or behavioral strategies to reduce the effect of expectation violation experiences, and hereby contributing to expectation maintenance despite expectation contradicting events. We postulate that the development of immunization strategies could help to better understand the transition from episodic to chronic depression. While in early periods of depression development, a focus on expectation change might be sufficient in treatment, the treatment of patients with chronic depression requires addressing these cognitive and behavioral immunization strategies more intensively. Further implications for treatment and research are outlined that are derived from this balance between expectation violation and cognitive immunization in depression. A focus on “expectations” helps to better understand the maintenance of depression We offer a model that explains why depression persists even in the presence of positive experiences. Many psychological treatments focus on the violation of negative expectations, but cognitive immunization can hinder treatment success. We suggest strategies on how to improve psychological treatments for depression by maximizing expectation violation, and minimizing cognitive immunization. A focus on “expectations” helps to better understand the maintenance of depression We offer a model that explains why depression persists even in the presence of positive experiences. Many psychological treatments focus on the violation of negative expectations, but cognitive immunization can hinder treatment success. We suggest strategies on how to improve psychological treatments for depression by maximizing expectation violation, and minimizing cognitive immunization.
Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

Dibutylphthalate (DBP), di(2-ethylhexyl)phthalate (DEHP), and di(2-ethylhexyl)adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα) and humanized PPARα (hPPARα) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR.
Optimal (up to polylog factors) sequential and parallel algorithms for approximating complex polynomial zeros

Our new algorithms for approximating all the complex zeros of an n-th degree polynomial I}(:L ) save both Boolean and arithmetic sequential tim(’, vcrsus the previous best algorithms of Schtinl)agc 1982, Pan 1987, and Neff and Reif 1994. In parallc] (N(;) implementation, we dramatically decrease t] le nl llnber of processors, versus the parallel algtw]thln of Neff 1994, which was the oldy NC alg’oritlml kn(nv]] for this problem so far. [Jndcr the sin]ple nor]) lalization assumption that the variable x has been S~ill(’fl so as to confine the zeros of p(:r;) to Llic 1u lit (Iisc {$ : [xl S 1}, our algorithms (wllicil pr{,ll,ise L,, be practically effective) approximate al] t I IC ZCNM of P(Z) within the absolute error bound 2–6, by using order of n arithmetic opera ti{ms and {m{ler of (b + n)n2 Boolean (bitwise) operations (i I) botl ) cases within polylog factors). The algori thins allow their optimal (work preserving) NC parall(l izatiol 1, so that they can be implemented by mil~g pf )1yl{ )g time and the order-s of n arithmetic promss(ws or (b+n)n2 Boolean processors. All cited bo(lnds 011Ll)c computational complexity aw wttki.r~, POl~logfJr/tl). ~JtiL: factor-s from the optmuT7L (in trmns of 77 a]ld h) Iilldcr both arithmetic and Boolean models of cmnpl Itat ion [in the Boolean case, under the additional (realistic) amrmption that n = 0(1})]. lSupported by NSF Grant, C(! R 9(}2(NW0 and PSC ( ~(1KY Awards Nos. 664334 and 665:301 Permission to copy without fee all or part of this material is granted provided that the copies are not made or distributed for direct commercial advantage, the ACM copyright notice and the title of the publication and lts date appear, and notice is given that copyin is by permission of the Association of Computing Machine~. o cop otherwise, or to republish, requires y “r a fee and/or specI ICpermission. STOC’ 95, Las Vegas, Nevada, USA
Pancreatic Tumor Suppression by Benzyl Isothiocyanate Is Associated with Inhibition of PI3K/AKT/FOXO Pathway

Purpose: Our previous studies have shown that benzyl isothiocyanate (BITC) suppress pancreatic cancer growth by inducing apoptosis but the molecular mechanism was unclear. In this study we hypothesized the involvement of PI3K/AKT/FOXO pathway in BITC-induced apoptosis. Experimental Design: Mice were implanted BxPC-3 tumor xenografts and orally gavaged with 12 μmol BITC. Plasma and tumor BITC concentration was estimated by liquid chromatography/tandem mass spectrometry. BxPC-3 and PanC-1 cells were used to elucidate PI3K/AKT/FOXO pathway. Electrophoretic mobility shift assay (EMSA), DNA binding activity, immunofluorescence, and gene transfection were used to delineate the mechanism. Results: BITC-treated mice showed 43% less tumor growth as compared with control mice and correlated well with the therapeutic concentrations of 6.5 μmol/L BITC achieved in plasma and 7.5 μmol/g BITC in tumor tissue. Western blot analyses and immunohistochemistry revealed that tumors from BITC-treated mice showed reduced phosphorylation of PI3K, AKT, PDK1, mTOR, FOXO1, and FOXO3a and increased apoptosis. Complementing our in vivo results, we made similar observations in a dose- and time-dependent manner in BITC-treated BxPC-3 and Panc-1 cells. Binding of FOXO1 with 14-3-3 proteins was also reduced drastically by BITC treatment indicating nuclear retention of FOXO1 and this observation was further confirmed with EMSA, immunofluorescence, DNA binding, and upregulation of FOXO-responsive proteins Bim, p27, and p21 in BxPC-3 cells. Overexpression of AKT by transient transfection significantly blocked the modulation of FOXO proteins and protected the cells from BITC-mediated apoptosis and growth suppression. Conclusions: Our results provide convincing evidence on the involvement of PI3K/AKT/FOXO pathway in BITC-mediated pancreatic tumor growth suppression. Clin Cancer Res; 17(7); 1784–95. ©2011 AACR.
Local Housing Markets and Segregation in England

In this article, Geoff Meen discusses patterns of economic segregation in England. Despite the emphasis that the government places on reducing segregation, patterns have, in fact, remained remarkably constant over, at least, the last twenty years. Dynamic changes in housing markets and migration over time help to explain these patterns, and evidence is presented on the extent to which house prices in certain local authorities have been under- or over-valued. The analysis also shows that, at the local level, housing markets exhibit non-linear behaviour, which hinders the effectiveness of housing policy in the most deprived areas and adds to economic segregation.
Improved fingerprint image segmentation using new modified gradient based technique

An important step in fingerprint recognition is the segmentation of the region of interest (ROI). The objective of fingerprint segmentation is to extract the region of interest (ROI) which contains the desired fingerprint impression. Fingerprint image segmentation highly influences the performances of automatic fingerprint identification system (AFIS). We present in this paper, a Modified Gradient Based Method to extract ROI. The distinct feature of our technique is that it gives high accurate segmentation percentage for fingerprint images even in case of low quality fingerprint images. The proposed algorithm is applied on FVC2004 database. Experimental results demonstrate the improved performance of the proposed scheme.
Counter-Changing Luminance: A Non-Fourier, Nonattentional Basis for the Perception of Single-Element Apparent Motion

Motion perception was studied for generalized apparent motion stimuli composed of 2 simultaneously visible elements whose luminance alternated between 2 values (only 1 element is visible at a time for standard apparent motion). It was demonstrated that 1st-order motion energy is neither necessary nor sufficient for the perception of apparent motion. Instead, it was found that counter-changing luminance— simultaneous luminance changes at 2 element locations—is the informational basis for perceiving luminance-defined apparent motion: Motion starts where luminance changes toward the background luminance value and ends where luminance changes away from the background luminance. The results were not attributable to either 2nd-order motion mechanisms (for which rectification precedes the computation of motion energy) or attention-based, 3rd-order motion mechanisms. Single-element apparent motion has been a central perceptual phenomenon since the earliest days of experimental psychology (Exner, 1875; Wertheimer, 1912). In the standard version, a visual element, say a spot of light, is alternately presented against a dark background in one of two nearby spatial locations; it appears for a finite period of time in one location and almost instantly disappears and reappears for a finite period of time in its other location. Over a wide range of spatial and temporal conditions, a single element is perceived moving smoothly through the space between
A tracking repositioning algorithm using keypoint labeling

This paper reports some work undertaken during the development of a generic object tracking application based on a keypoint model. In our previous work, we proposed a keypoint labeling algorithm to distinguish object from background keypoints. This article is the continuation of this work and deals with the problem of handling object deformation using the keypoint labels. In consequence, we introduce an algorithm to refine the bounding box position according to the surrounding keypoint labels. Experimental results are shown to validate this theory.
Analyzing Time Complexity of Parallel Algorithms for Knapsack Problem

In this paper, we have analyzed various parallel algorithms for solving knapsack problem and proposed an efficient approach for solving knapsack problem using an approximation algorithm. We also discussed the time complexity of different algorithm. Backtracking is not discussed here due to its inherent sequential property. The validity of the proposed algorithm is demonstrated on a worked out example and it shows the superiority of the proposed algorithm
The Transformation of Professionals into Self-Managing and Partially Self-Designing Contributors: Toward a Theory of Leadership-Making

Abstract Self-managing teams are rapidly approaching the popularity of Quality Circles in both the popular and organiza-tional literature. However, before this promising notion becomes the next panacea for the ills of our declining inter-national competitiveness, we must investigate the fundamental question of how superior managed professionals be-come transformed into self-managers. This paper presents a model of a leadership-making process which purports to produce the transformation of superior manager professionals into self-managing and partially self-designing units. The focus of this paper is on the upper end of the self- managing category of Hackman’s (1986) authority matrix. A life cycle model of leadership-making is outlined, and emphasis is placed on the process by which teamwork is built from within and the activities which allow individuals to (a) outgrow their dependence on outside direction and con-trol and (b) realize that a more effective strategy for accomplishing their own (“I”’) needs is through satisfying learn (“We”) needs (i.e., the “transformation”). This model for the process of becoming a self-managing team player pro-vides a data-grounded rationale (covering over 20 years of programmatic research) in order to facilitate hypothesis-testing research.
Requirements for Transitional Endoplasmic Reticulum Site Structure and Function in Saccharomyces cerevisiae

Secretory proteins are exported from the ER at specialized regions known as transitional ER (tER). COPII proteins are enriched at tER sites, but mechanisms underlying assembly and maintenance are unclear. This study characterizes tER sites in Saccharomyces cerevisiae and probes protein and lipid requirements for tER site structure and function.
In vivo Target Modulation and Biological Activity of CHIR-258, a Multitargeted Growth Factor Receptor Kinase Inhibitor, in Colon Cancer Models

Purpose: To evaluate the therapeutic and biological effects of CHIR-258, an orally bioavailable, potent inhibitor of class III-V receptor tyrosine kinases, in colon cancer models. Experimental Design: The pharmacologic activity of CHIR-258 was characterized by monitoring target modulation as well as by evaluating the antitumor and antiangiogenic effects in human colon xenograft models. Results: CHIR-258 inhibits vascular endothelial growth factor receptor 1/2, fibroblast growth factor receptor 1/3, and platelet-derived growth factor receptor β (PDGFRβ) and shows both antitumor and antiangiogenic activities in vivo. Treatment of KM12L4a human colon cancer cells with CHIR-258 resulted in a dose-dependent inhibition of vascular endothelial growth factor receptor 1 and PDGFRβ phosphorylation and reduction of phosphorylated extracellular signal-regulated kinase (ERK) levels, indicating modulation of target receptors and downstream signaling. In vivo administration of CHIR-258 resulted in significant tumor growth inhibition and tumor regressions, including large, established tumors (500-1,000 mm3). Immunohistochemical analysis showed a reduction of phosphorylated PDGFRβ and phosphorylated ERK in tumor cells after oral dosing with CHIR-258 compared with control tumors. These changes were accompanied by decreased tumor cell proliferation rate and reduced intratumoral microvessel density. CHIR-258 inhibited the phosphorylation of PDGFRβ and ERK phosphorylation in tumors within 2 hours following dosing and the inhibitory activity was sustained for >24 hours. Significant antitumor activity was observed with intermittent dosing schedules, indicating a sustained biological activity. Conclusion: These studies provide evidence that biological activity of CHIR-258 in tumors correlates with efficacy and aids in the identification of potential biomarkers of this multitargeted receptor tyrosine kinase inhibitor. CHIR-258 exhibits properties that make it a promising candidate for clinical development in a variety of solid and hematologic malignancies.