bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compiling self-adjusting programs with continuations
Authors: Ley-Wild Ruy , Fluet Matthew , Acar Umut A. 
Published: September 2008

Self-adjusting programs respond automatically and efficiently to input changes by tracking the dynamic data dependences of the computation and incrementally updating the output as needed. In order to identify data dependences, previously proposed approaches require the user to make use of a set of monadic primitives. Rewriting an ordinary program into a self-adjusting program with these primitives, however, can be difficult and error-prone due to various monadic and proper-usage restrictions, some of which cannot be enforced statically. Previous work therefore suggests that self-adjusting computation would benefit from direct language and compiler support.
In this paper, we propose a language-based technique for writing and compiling self-adjusting programs from ordinary programs. To compile self-adjusting programs, we use a continuation-passing style (cps) transformation to automatically infer a conservative approximation of the dynamic data dependences. To prevent the inferred, approximate dependences from degrading the performance of change propagation, we generate memoized versions of cps functions that can reuse previous work even when they are invoked with different continuations. The approach offers a natural programming style that requires minimal changes to existing code, while statically enforcing the invariants required by self-adjusting computation.
We validate the feasibility of our proposal by extending Standard ML and by integrating the transformation into MLton, a whole-program optimizing compiler for Standard ML. Our experiments indicate that the proposed compilation technique can produce self-adjusting programs whose performance is consistent with the asymptotic bounds and experimental results obtained via manual rewriting (up to a constant factor).
The Possibilities of New Perspectives for Social Sciences: An Analysis Based on Ibn Khaldun's Theory of Umrân
Authors: Yaslıçimen Faruk , Sunar Lütfi 
Published: September 2008

AbstractThe major obstacle in reinterpreting and reconstructing the cultural accumulation of the Civilisation of Islam is not only the unawareness of Muslim scholars of their heritage, but also their willingness to employ western perspectives to utilise this heritage. In order to overcome this tragedy, social sciences should be criticised through vivid and constructive analyses; and Islamic scientific tradition should be reinterpreted in a comprehensive manner. Instead of basic model transfers from the west, the original sources should be re-analysed. Ibn Khaldun and his Muqaddimah present an invaluable opportunity in that respect. However, modern scholarship contextualises Ibn Khaldun in anachronic ways, which in turn preclude the possibility of reproducing new scientific traditions. Indeed, Ibn Khaldun's conception of science rises on three pillars, complementing one another that are a comprehensive perception of universe, a historical consciousness, and a metaphysics of society. These three factors are interrelatedly systematised in the 'ilm al-umrân whose main theme of reference is tawhid in the traditional Islamic thought. Different stages of knowledge overlap in the epistemology of The Muqaddimah. The basic principles of Islamic thought are systematised in the framework of Qur'anic ontological presumptions. Hence, the principles of common origin of the existence, tawhid, and the hierarchical absolution of Allah were continued. Therefore, this article will offer the Umrân (scienza nouva) of Ibn Khaldun as an opportunity to release the social sciences from its ontological dilemmas.
The Sociology of Civilisations: Ibn Khaldun and a Multi-Civilisational World Order
Authors: Nizamuddin Ali , Şentürk Recep 
Published: September 2008

AbstractDue to advancements in telecommunications and transportation over the past century, the world is shrinking and physical boundaries are being eroded. The advent of globalization has facilitated the flow of ideas, values, goods, and people from one part of the world to another. This hyperbolic human activity has altered the structure of inter-civilizational relations and has spawned a spirited debate on how to create a multi-civilizational world order. This paper is critical of contemporary approaches on the subject that envisage the primacy of one civilization on the one hand and a clash among civilizations on the other. By examining Ibn Khaldun's theory of 'Umrān and the discipline of Fiqh, it argues that these concepts remain relevant for our understanding of the human condition today. While the theory of Umrān analyzes political and economic relations at the macro-level, Fiqh tries to arrange societal relations at the micro-level. This paper also studies the Ottoman legacy since the Ottoman state was founded on Fiqh and the Millet system. It proved to be successful in preserving pluralistic communities based on principles of autonomy and mutual coexistence. Even though Ibn Khaldun was one of the pioneers in the field of civilizational studies, his seminal work is largely neglected in scholarly circles today, both Muslim and non-Muslim alike. The present inquiry seeks to address this shortcoming.
Oral Histories in the Making of Our Memories and Heritage
Authors: Guan Kwa Chong 
Published: September 2008

AbstractThe paper argues that our understanding and use of oral history interviewing for reconstruction of our past or life narratives will need to be reviewed as our concept of how our memories work changes. Our current practice of oral history interviewing assumes that the oral history interviewees are providing us an accurate recollection of their memories and which the interviewer attempts to verify with the interviewees through cross-checking with other historical evidence. This practice of oral history interviewing assumes that our mind is a blank slate upon which our memories are inscribed to be recalled. However, an alternative understanding of our memory assumes that our memories are not static, but filter from our past to our present, mix with other more recent memories, and are reconfigured according to current preoccupations. Thus what our oral history interviewees reveal are their memories configured to their present preoccupations and what they decide to reveal is often a moral choice of what they perceive to be the relevance of that memory to the interview.
The Life of Pons de Léras: Knights and Conversion to Religious Life in the Twelfth Century
Authors: Berman Constance 
Published: September 2008

AbstractComparing the Life of Pons de Léras with the evidence of charters for a variety of Cistercian abbeys allows us to conclude that the term conversus as applied in the charters to Pons in fact meant “convert to the religious life.” Only in the 1150s did peasant recruits as lay brothers appear at Silvanès and elsewhere. That Pons is referred to as conversus therefore does not require an explanation of humility.
How Teachers Experience Principal Leadership: The Roles of Professional Community, Trust, Efficacy, and Shared Responsibility
Authors: Wahlstrom Kyla L. , Louis Karen Seashore 
Published: September 2008

Purpose: The leadership of the principal is known to be a key factor in supporting student achievement, but how that leadership is experienced and instructionally enacted by teachers is much less clear. The purpose of this study was to examine various factors that are often present in principal—teacher interactions and teacher—teacher relationships to see how those may have an impact on teachers' classroom instructional practices. Data Collection and Analysis: Data for this quantitative study are from a teacher survey developed for the national research project, Learning from Leadership, funded by the Wallace Foundation. There are 4,165 completed surveys in the database, which reflects responses from teachers in grades K-12 in a sample of schools across the United States. Using a conceptual framework based on various known components of effective schools today, a stepwise linear regression examined the relationships among practices such as shared leadership and professional community with contextual variables such as trust and efficacy. Findings: Three types of instructional behaviors—Standard Contemporary Practice, Focused Instruction, and Flexible Grouping Practices—emerged as strong factors which operationally described effective teacher practice. The presence of shared leadership and professional community explain much of the strength among the three instructional variables. Furthermore, the effect of teachers' trust in the principal becomes less important when shared leadership and professional community are present. Self-efficacy strongly predicts Focused Instruction, but it has less predictive value for the other measures of instructional behavior. Individual teacher characteristics of gender and years of experience have clear impact on instructional practice, but there are no discernible patterns that suggest that the level of the principal (elementary vs. secondary) have more or less influence on teacher instructional behaviors. Conclusions: Increasing our knowledge about what leaders do and how they have an impact on the instructional behaviors of teachers will lead us to a better understanding of how leadership has a direct relationship to improved student achievement. These findings create a clearer picture of teacher—principal and teacher—teacher interactions that support learning and bring us closer to the elusive goal of clarifying the link between leadership and learning.
Down-regulation of hepcidin in porphyria cutanea tarda
Authors: Ajioka Richard S. , Phillips John D. , Weiss Robert B. , Dunn Diane M. , Smit Maria W. , Proll Sean C. , Katze Michael G. , Kushner James P. 
Published: September 2008

Abstract
Hepatic siderosis is common in patients with porphyria cutanea tarda (PCT). Mutations in the hereditary hemochromatosis (hh) gene (HFE) explain the siderosis in approximately 20% patients, suggesting that the remaining occurrences result from additional genetic and environmental factors. Two genes known to modify iron loading in hh are hepcidin (HAMP) and hemojuvelin (HJV). To determine if mutations in or expression of these genes influenced iron overload in PCT, we compared sequences of HAMP and HJV in 96 patients with PCT and 88 HFE C282Y homozygotes with marked hepatic iron overload. We also compared hepatic expression of these and other iron-related genes in a group of patients with PCT and hh. Two intronic polymorphisms in HJV were associated with elevated serum ferritin in HFE C282Y homozygotes. No exonic polymorphisms were identified. Sequencing of HAMP revealed exonic polymorphisms in 2 patients with PCT: heterozygosity for a G→A transition (G71D substitution) in one and heterozygosity for an A→G transition (K83R substitution) in the other. Hepatic HAMP expression in patients with PCT was significantly reduced, regardless of HFE genotype, when compared with patients with hh but without PCT with comparable iron overload. These data indicate that the hepatic siderosis associated with PCT likely results from dysregulated HAMP.
Genetic perturbation of the putative cytoplasmic membrane-proximal salt bridge aberrantly activates α4 integrins
Authors: Imai Yoichi , Park Eun Jeong , Peer Dan , Peixoto António , Cheng Guiying , von Andrian Ulrich H. , Carman Christopher V. , Shimaoka Motomu 
Published: September 2008

Abstractα4 integrins play a pivotal role in leukocyte migration and tissue-specific homing. The ability of integrins to bind ligand is dynamically regulated by activation-dependent conformational changes triggered in the cytoplasmic domain. An NMR solution structure defined a putative membrane-proximal salt bridge between the αIIbβ3 integrin cytoplasmic tails, which restrains integrins in their low-affinity state. However, the physiological importance of this salt bridge in α4 integrin regulation remains to be elucidated. To address this question, we disrupted the salt bridge in murine germ line by mutating the conserved cytoplasmic arginine RGFFKR in α4 integrins. In lymphocytes from knock-in mice (α4-R/AGFFKR), α4β1 and α4β7 integrins exhibited constitutively up-regulated ligand binding. However, transmigration of these cells across VCAM-1 and MAdCAM-1 substrates, or across endothelial monolayers, was reduced. Perturbed detachment of the tail appeared to cause the reduced cell migration of α4-R/AGFFKR lymphocytes. In vivo, α4-R/AGFFKR cells exhibited increased firm adhesion to Peyer patch venules but reduced homing to the gut. Our results demonstrate that the membrane-proximal salt bridge plays a critical role in supporting proper α4 integrin adhesive dynamics. Loss of this interaction destabilizes the nonadhesive conformation, and thereby perturbs the properly balanced cycles of adhesion and deadhesion required for efficient cell migration.
Dendritic cells drive memory CD8 T-cell homeostasis via IL-15 transpresentation
Authors: Stonier Spencer W. , Ma Lisa J. , Castillo Eliseo F. , Schluns Kimberly S. 
Published: September 2008

AbstractInterleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15Rα+ DCs through the preferential enhancement of a subset of KLRG-1+CD27− CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells, suggesting that memory CD8 T cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T-cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis.
HapMap scanning of novel human minor histocompatibility antigens
Authors: Kamei Michi , Nannya Yasuhito , Torikai Hiroki , Kawase Takakazu , Taura Kenjiro , Inamoto Yoshihiro , Takahashi Taro , Yazaki Makoto , Morishima Satoko , Tsujimura Kunio , Miyamura Koichi , Ito Tetsuya , Togari Hajime , Riddell Stanley R. , Kodera Yoshihisa , Morishima Yasuo , Takahashi Toshitada , Kuzushima Kiyotaka , Ogawa Seishi , Akatsuka Yoshiki 
Published: September 2008

AbstractMinor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.
NF-kappaB mediates the survival of human bronchial epithelial cells exposed to cigarette smoke extract
Authors: Liu Xiangde , Togo Shinsaku , Al-Mugotir Mona , Kim Huijung , Fang QiuHong , Kobayashi Tetsu , Wang XingQi , Mao Lijun , Bitterman Peter , Rennard Stephen 
Published: September 2008

Abstract

Background
We have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial cells (HBECs), and that IL-6/STAT3 signaling contributes to the cell survival. Since NF-κB is also involved in regulating apoptosis and cell survival, the current study was designed to investigate the role of NF-κB in mediating cell survival in response to cigarette smoke exposure in HBECs.

Methods
Both the pharmacologic inhibitor of NF-κB, curcumin, and RNA interference targeting p65 were used to block NF-κB signaling in HBECs. Apoptosis and cell survival were then assessed by various methods including COMET assay, LIVE/DEAD Cytotoxicity/Viability assay and colony formation assay.

Results
Cigarette smoke extract (CSE) caused DNA damage and cell cycle arrest in S phase without leading to apoptosis in HBECs as evidenced by TUNEL assay, COMET assay and DNA content assay. CSE stimulated NF-κB -DNA binding activity and up-regulated Bcl-XL protein in HBECs. Inhibition of NF-κB by the pharmacologic inhibitor curcumin (20 μM) or suppression of p65 by siRNA resulted in a significant increase in cell death in response to cigarette smoke exposure. Furthermore, cells lacking p65 were incapable of forming cellular colonies when these cells were exposed to CSE, while they behaved normally in the regular culture medium.

Conclusion
The current study demonstrates that CSE activates NF-κB and up-regulates Bcl-XL through NF-kB activation in HBECs, and that CSE induces cell death in cells lacking p65. These results suggest that activation of NF-κB regulates cell survival following DNA damage by cigarette smoke in human bronchial epithelial cells.
The Serine/threonine kinase Stk33 exhibits autophosphorylation and phosphorylates the intermediate filament protein Vimentin
Authors: Brauksiepe Bastienne , Mujica Alejandro O , Herrmann Harald , Schmidt Erwin R 
Published: September 2008

Abstract

Background
Colocalization of Stk33 with vimentin by double immunofluorescence in certain cells indicated that vimentin might be a target for phosphorylation by the novel kinase Stk33. We therefore tested in vitro the ability of Stk33 to phosphorylate recombinant full length vimentin and amino-terminal truncated versions thereof. In order to prove that Stk33 and vimentin are also in vivo associated proteins co-immunoprecipitation experiments were carried out. For testing the enzymatic activity of immunoprecipitated Stk33 we incubated precipitated Stk33 with recombinant vimentin proteins. To investigate whether Stk33 binds directly to vimentin, an in vitro co-sedimentation assay was performed.

Results
The results of the kinase assays demonstrate that Stk33 is able to specifically phosphorylate the non-α-helical amino-terminal domain of vimentin in vitro. Furthermore, co-immunoprecipitation experiments employing cultured cell extracts indicate that Stk33 and vimentin are associated in vivo. Immunoprecipitated Stk33 has enzymatic activity as shown by successful phosphorylation of recombinant vimentin proteins. The results of the co-sedimentation assay suggest that vimentin binds directly to Stk33 and that no additional protein mediates the association.

Conclusion
We hypothesize that Stk33 is involved in the in vivo dynamics of the intermediate filament cytoskeleton by phosphorylating vimentin.
FERN – a Java framework for stochastic simulation and evaluation of reaction networks
Authors: Erhard Florian , Friedel Caroline C , Zimmer Ralf 
Published: September 2008

Abstract

Background
Stochastic simulation can be used to illustrate the development of biological systems over time and the stochastic nature of these processes. Currently available programs for stochastic simulation, however, are limited in that they either a) do not provide the most efficient simulation algorithms and are difficult to extend, b) cannot be easily integrated into other applications or c) do not allow to monitor and intervene during the simulation process in an easy and intuitive way. Thus, in order to use stochastic simulation in innovative high-level modeling and analysis approaches more flexible tools are necessary.

Results
In this article, we present FERN (Framework for Evaluation of Reaction Networks), a Java framework for the efficient simulation of chemical reaction networks. FERN is subdivided into three layers for network representation, simulation and visualization of the simulation results each of which can be easily extended. It provides efficient and accurate state-of-the-art stochastic simulation algorithms for well-mixed chemical systems and a powerful observer system, which makes it possible to track and control the simulation progress on every level. To illustrate how FERN can be easily integrated into other systems biology applications, plugins to Cytoscape and CellDesigner are included. These plugins make it possible to run simulations and to observe the simulation progress in a reaction network in real-time from within the Cytoscape or CellDesigner environment.

Conclusion
FERN addresses shortcomings of currently available stochastic simulation programs in several ways. First, it provides a broad range of efficient and accurate algorithms both for exact and approximate stochastic simulation and a simple interface for extending to new algorithms. FERN's implementations are considerably faster than the C implementations of gillespie2 or the Java implementations of ISBJava. Second, it can be used in a straightforward way both as a stand-alone program and within new systems biology applications. Finally, complex scenarios requiring intervention during the simulation progress can be modelled easily with FERN.
PredGPI: a GPI-anchor predictor
Authors: Pierleoni Andrea , Martelli Pier Luigi , Casadio Rita 
Published: September 2008

Abstract

Background
Several eukaryotic proteins associated to the extracellular leaflet of the plasma membrane carry a Glycosylphosphatidylinositol (GPI) anchor, which is linked to the C-terminal residue after a proteolytic cleavage occurring at the so called ω-site. Computational methods were developed to discriminate proteins that undergo this post-translational modification starting from their aminoacidic sequences. However more accurate methods are needed for a reliable annotation of whole proteomes.

Results
Here we present PredGPI, a prediction method that, by coupling a Hidden Markov Model (HMM) and a Support Vector Machine (SVM), is able to efficiently predict both the presence of the GPI-anchor and the position of the ω-site. PredGPI is trained on a non-redundant dataset of experimentally characterized GPI-anchored proteins whose annotation was carefully checked in the literature.

Conclusion
PredGPI outperforms all the other previously described methods and is able to correctly replicate the results of previously published high-throughput experiments. PredGPI reaches a lower rate of false positive predictions with respect to other available methods and it is therefore a costless, rapid and accurate method for screening whole proteomes.