gebhart/patrepeval huggingface dataset:
Query-Based Debugging (1999)

Object relationships in modern software systems are becoming increasingly numerous and complex. Program errors due to violations of object relationships are hard to find because of the cause-effect gap between the time when an error occurs and the time when the error becomes apparent to the programmer. Although debugging techniques such as conditional and data breakpoints help to find error causes in simple cases, they fail to effectively bridge the cause-effect gap in many situations. Programmers need new tools that allow them to explore objects in a large system more efficiently and to detect broken object relationships instantaneously. 
Many existing debuggers present only a low-level, one-object-at-a-time view of objects and their relationships. We propose a new solution to overcome these problems: query-based debugging. The implementation of the query-based debugger described here offers programmers an effective query tool that allows efficient searching of large object spaces and quick verification of complex relationships. Even for programs that have large numbers of objects, the debugger achieves interactive response times for common queries by using a combination of fast searching primitives, query optimization, and incremental result delivery. 
Dynamic query-based debuggers extend query-based debugging by providing instant error alerts. In other words, they continuously check inter-object relationships while the debugged program is running. To speed up dynamic query evaluation, our debugger (implemented in portable Java) uses a combination of program instrumentation, load-time code generation, query optimization, and incremental reevaluation. Experiments and a query cost model show that selection queries are efficient in most cases, while more costly join queries are practical when query evaluations are infrequent or query domains are small. 
We thus demonstrate that query-based debugging is a useful method that can be efficiently implemented and effectively used in program debugging.
Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: atopic dermatitis, psoriasis and skin mastocytosis (2014)

Chemokines are signaling peptides which regulate cell trafficking and provide control of the tissue-specific cell homing. In the skin, chemokines are secreted both by the resident cells such as keratinocytes, melanocytes, fibroblasts, dendritic cells and mast cells, as well as by infiltrated cells - lymphocytes, eosinophils, and monocytes. Chemokines, together with cytokines, participate in induction and maintenance of inflammation in the skin and regulate the composition of the cellular infiltrates. Inflammation within the skin is a feature shared by atopic dermatitis and psoriasis, two of the most common dermatoses. Accumulation of activated mast cells in the affected skin is seen both in atopic dermatitis and in psoriasis. This paper presents a concise overview of the current knowledge on the role chemokines have in pathogenesis of atopic dermatitis, psoriasis, and mastocytosis, a disease caused directly by the accumulation and activation of mast cells in the skin.
Integration-defective lentiviral vector mediates efficient gene editing through homology-directed repair in human embryonic stem cells (2016)

Human embryonic stem cells (hESCs) are used as platforms for disease study, drug screening and cell-based therapy. To facilitate these applications, it is frequently necessary to genetically manipulate the hESC genome. Gene editing with engineered nucleases enables site-specific genetic modification of the human genome through homology-directed repair (HDR). However, the frequency of HDR remains low in hESCs. We combined efficient expression of engineered nucleases and integration-defective lentiviral vector (IDLV) transduction for donor template delivery to mediate HDR in hESC line WA09. This strategy led to highly efficient HDR with more than 80% of the selected WA09 clones harboring the transgene inserted at the targeted genomic locus. However, certain portions of the HDR clones contained the concatemeric IDLV genomic structure at the target site, probably resulted from recombination of the IDLV genomic input before HDR with the target. We found that the integrase protein of IDLV mediated the highly efficient HDR through the recruitment of a cellular protein, LEDGF/p75. This study demonstrates that IDLV-mediated HDR is a powerful and broadly applicable technology to carry out site-specific gene modification in hESCs.
Assessing the Effects of Enhanced Supply Chain Visibility Through RFID. (2008)

The majority of RFID implementations can be traced back either to mandates issued by companies or institutions with significant market power like Wal-Mart or the U.S. Department of Defense, or to the replacement of existing Auto-ID technologies like barcodes. Only sporadically is RFID being used to derive superior information about current processes in order to create supply chain visibility. In this contribution, we examine the visibility potentials of RFID technology within the context of SCM and we propose a four-step approach to assessing the results that can be achieved through visibility.
Evaluation of Wave Drag Reduction by Flow Control (2005)

An analytical expression is proposed to estimate the wave drag of an aerofoil equipped with shock control. The analysis extends the conventional approach for a single normal shock wave in the absence of control, based on the knowledge that all types of successful shock control on transonic aerofoils cause bifurcated λ-shock structures. The influence of surface curvature on the λ-shock structure has been taken into account. The extended method has been found to produce fairly good agreement with the results obtained by CFD methods while requiring negligible computational effort. This new formulation is expected to be beneficial in the industrial design process of transonic aerofoils and wings where a large number of computational simulations have to be performed.
Effect of storage on physical and functional properties of extracellular vesicles derived from neutrophilic granulocytes (2014)

Storage significantly alters both the physical and functional properties of EVs even if the number of EVs stays constant. If storage is needed, EVs should be kept at -80°C, preferably not longer than 7 days. For functional tests, freshly prepared EVs are recommended.
Inhibition of angiogenesis and intrahepatic growth of colon cancer by TAC-101. (1999)

We demonstrated in this study that inhibition of intra-hepatic growth of colon cancer by TAC-101 is mediated by inhibition of angiogenesis. In vitro experiments showed that TAC-101 inhibited the proliferation of murine hepatic sinusoidal endothelial (HSE) cells induced by coculture with murine colon 26-L5 (L5) cells. HSE cell proliferation was also enhanced by conditioned medium of L5 cells (CM-L5), and this enhancement of proliferation was abrogated by anti-vascular endothelial growth factor antibody. CM-L5 also induced in vitro tube formation of HSE cells on Matri-gel, and this activity of CM-L5 was abrogated by TAC-101 in a concentration-dependent manner. On the other hand, p.o. administration of TAC-101 inhibited tumor-induced angiogenesis in vivo and decreased the weights of L5 tumors in the mouse liver. Reverse transcriptase-PCR analysis using in vivo tumor tissue suggested that repression of vascular endothelial growth factor expression by TAC-101 was associated with the antiangiogenic activity. TAC-101 alone and 5-fluorouracil (5-FU)/D,L-leucovorin (LV) significantly inhibited the intrahepatic growth of L5 tumors (P = 0.002 and 0.001, respectively), whereas 5-FU alone did not (P = 0.088). When TAC-101 was administered with 5-FU/LV, marked enhancement of antitumor activity was observed (95% inhibition; P<0.001). This enhanced antitumor effect was also observed in experiments using Co-3 human colon adenocarcinoma. Concurrent treatment with TAC-101 and 5-FU/LV and sequential treatment with 5-FU/LV followed by TAC-101 resulted in significant augmentation of antitumor activity against Co-3 (overall P = 0.007 and 0.015, respectively). These findings indicate that TAC-101 inhibits tumor angiogenesis and suggest that it may be effective against hepatic metastasis of colon cancer.
Dendrite Development Regulated by the Schizophrenia-Associated Gene FEZ1 Involves the Ubiquitin Proteasome System (2014)

Downregulation of the schizophrenia-associated gene DISC1 and its interacting protein FEZ1 positively regulates dendrite growth in young neurons. However, little is known about the mechanism that controls these molecules during neuronal development. Here, we identify several components of the ubiquitin proteasome system and the cell-cycle machinery that act upstream of FEZ1. We demonstrate that the ubiquitin ligase cell division cycle 20/anaphase-promoting complex (Cdc20/APC) controls dendrite growth by regulating the degradation of FEZ1. Furthermore, dendrite growth is modulated by BubR1, whose known function so far has been restricted to control Cdc20/APC activity during the cell cycle. The modulatory function of BubR1 is dependent on its acetylation status. We show that BubR1 is deacetylated by Hdac11, thereby disinhibiting the Cdc20/APC complex. Because dendrite growth is affected both in hippocampal dentate granule cells and olfactory bulb neurons upon modifying expression of these genes, we conclude that the proposed mechanism governs neuronal development in a general fashion.
Regulation and characterization of the galactose-phosphoenolpyruvate-dependent phosphotransferase system in Lactobacillus casei (1983)

Cells of Lactobacillus casei grown in media containing galactose or a metabolizable beta-galactoside (lactose, lactulose, or arabinosyl-beta-D-galactoside) were induced for a galactose-phosphoenolpyruvate-dependent phosphotransferase system (gal-PTS). This high-affinity system (Km for galactose, 11 microM) was inducible in eight strains examined, which were representative of all five subspecies of L. casei. The gal-PTS was also induced in strains defective in glucose- and lactose-phosphoenolpyruvate-dependent phosphotransferase systems during growth on galactose. Galactose 6-phosphate appeared to be the intracellular inducer of the gal-PTS. The gal-PTS was quite specific for D-galactose, and neither glucose, lactose, nor a variety of structural analogs of galactose caused significant inhibition of phosphotransferase system-mediated galactose transport in intact cells. The phosphoenolpyruvate-dependent phosphorylation of galactose in vitro required specific membrane and cytoplasmic components (including enzyme IIIgal), which were induced only by growth of the cells on galactose or beta-galactosides. Extracts prepared from such cells also contained an ATP-dependent galactokinase which converted galactose to galactose 1-phosphate. Our results demonstrate the separate identities of the gal-PTS and the lactose-phosphoenol-pyruvate-dependent phosphotransferase system in L. casei.
Efficient prediction of siRNAs with siRNArules 1.0: An open-source JAVA approach to siRNA algorithms (2006)

RNAi interference and siRNA have become useful tools for investigation of gene function. However, the discovery that not all siRNA are equally efficient made necessary screens or design algorithms to obtain high activity siRNA candidates. Several algorithms have been published, but they remain inefficient, obscure, or commercially restricted. This article describes an open-source JAVA program that is surprisingly efficient at predicting active siRNAs (Pearson correlation coefficient r = 0.52, n = 526 siRNAs). Furthermore, this version 1.0 sets the stage for further improvement of the free code by the open-source community (http://sourceforge.net/).
Efficient Adenovector CD40 Ligand Immunotherapy of Canine Malignant Melanoma (2008)

Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.
Ortho effect in hydrolysis of phenyl esters (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrtho effect in hydrolysis of phenyl estersTakaaki Nishioka, Toshio Fujita, Koji Kitamura, and Minoru NakajimaCite this: J. Org. Chem. 1975, 40, 17, 2520–2525Publication Date (Print):August 1, 1975Publication History Published online1 May 2002Published inissue 1 August 1975https://pubs.acs.org/doi/10.1021/jo00905a022https://doi.org/10.1021/jo00905a022research-articleACS PublicationsRequest reuse permissionsArticle Views778Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Contributions of glycolysis and oxidative phosphorylation to adenosine 5'-triphosphate production in AS-30D hepatoma cells. (1984)

The AS-30D rat hepatoma cell line is characteristic of that class of rapidly growing tumors which exhibit high rates of aerobic glucose utilization and lactic acid production (Bustamante, E., Morris, H.P., and Pedersen, P.L., J. Biol. Chem., 256: 8699-8704, 1981). In this study, we have examined the coupling properties of the mitochondria in intact AS-30D hepatoma cells and the relative contributions of cytoplasmic (glycolytic) and mitochondrial compartments to total cellular ATP production in the presence of glucose and glutamine. All respiration in AS-30D cells was inhibited by inhibitors of mitochondrial electron transport, ruling out significant rates of respiration from other cellular components. Moreover, cellular respiration was found to be coupled to phosphorylation of ADP, as demonstrated by its inhibition by oligomycin and aurovertin, inhibitors of the mitochondrial ATP synthetase (F0F1-ATPase). When intact cells were supplied with glucose as the only added energy source, it was estimated that about 60% of the total cell ATP was derived from glycolysis and 40% from oxidative phosphorylation. Addition of physiological concentrations of glutamine in the presence of glucose had little effect on the relative contributions of glycolysis and oxidative phosphorylation to total cellular ATP production. In the absence of added glucose, glutamine alone could maintain the same ATP production rates by supporting mitochondrial oxidative phosphorylation. It is concluded that, in the AS-30D hepatoma cell line, glucose is the preferred energy source, with the larger portion of ATP production being supplied by glycolytic reactions. Although oxidative substrates such as glutamine can replace glucose in maintaining total cell ATP production, they do not appear to be the major fuel sources when hepatoma AS-30D cells are exposed to concentrations of substrates which occur in vivo.
SECUENCIACION DE CONTENIDOS Y OBJETOS DE APRENDIZAJE (II) (2006)

Esta es la segunda parte del artículo del mismo nombre publicado en el número anterior de RED, y que en conjunto constituyen una serie de tres que fueron publicados como un solo trabajo en español en el primer monográfico de RED dedicado a Objetos de Aprendizaje Reutilizables (http://www.um.es/ead/red/M2/zapata47.pdf). En él planteamos una visión de la selección y de la secuenciación de contenidos de enseñanza, en el contexto de la planificación curricular, desde la perspectiva de las corrientes del pensamiento constructivista. Señalamos la importancia de contar, en el campo de la formación apoyada en redes, con herramientas y criterios autónomos que guíen este proceso desde unas bases propias, externas y con preeminencia sobre las que derivan de la configuración de las herramientas tecnológicas, y desde la necesidad de contar con estándares de formato de intercambio de datos. Si en general este planteamiento es importante adquiere especial relevancia en el contexto del e-learning de propósito general, tanto en el de formación como en el e-learning empresarial o en el universitario. Y por supuesto en el contexto de la formación reglada y de formación informal, o de la no reglada. También señalamos las necesidades que plantea la industria del e-learning en la actualidad en relación con el diseño instruccional de objetos de aprendizaje, necesidades que constituyen una prioridad y un desafío. En la primera parte desarrollamos la perspectiva constructivista y la conceptualización de servicios y herramientas tecnológicas como recursos educativos, así como una revisión de los conceptos vinculados con el e-learning, objetos de aprendizaje, OAR y reusabilidad. En esta parte abordaremos la fundamentación de las teorías que rigen los procedimientos de selección de contenidos, los presupuestos básicos y la descripción de las técnicas de secuenciación. En particular nos centraremos en tres de ellas: La técnica de análisis de contenidos, la técnica de análisis de la tarea y la Teoría de la Elaboración. Por último como conclusión, en la tercera parte, intentaremos abordar, no en su resolución sino solo en su propuesta como enunciado, varias cuestiones: ¿el concepto de objeto de aprendizaje reusable es compatible con los requisitos de interdependencia de contenidos de aprendizaje? Y si es así ¿qué requisitos han de cumplir éstos?
Site-specific gene therapy for cardiovascular disease. (2010)

Gene therapy holds considerable promise for the treatment of cardiovascular disease and may provide novel therapeutic solutions for both genetic disorders and acquired pathophysiologies such as arteriosclerosis, heart failure and arrhythmias. Recombinant DNA technology and the sequencing of the human genome have made a plethora of candidate therapeutic genes available for cardiovascular diseases. However, progress in the field of gene therapy for cardiovascular disease has been modest; one of the key reasons for this limited progress is the lack of gene delivery systems for localizing gene therapy to specific sites to optimize transgene expression and efficacy. This review summarizes progress made toward the site-specific delivery of cardiovascular gene therapy and highlights selected promising novel approaches.
Learning class-specific affinities for image labelling (2008)

Spectral clustering and eigenvector-based methods have become increasingly popular in segmentation and recognition. Although the choice of the pairwise similarity metric (or affinities) greatly influences the quality of the results, this choice is typically specified outside the learning framework. In this paper, we present an algorithm to learn class-specific similarity functions. Mapping our problem in a Conditional Random Fields (CRF) framework enables us to pose the task of learning affinities as parameter learning in undirected graphical models. There are two significant advances over previous work. First, we learn the affinity between a pair of data-points as a function of a pairwise feature and (in contrast with previous approaches) the classes to which these two data-points were mapped, allowing us to work with a richer class of affinities. Second, our formulation provides a principled probabilistic interpretation for learning all of the parameters that define these affinities. Using ground truth segmentations and labellings for training, we learn the parameters with the greatest discriminative power (in an MLE sense) on the training data. We demonstrate the power of this learning algorithm in the setting of joint segmentation and recognition of object classes. Specifically, even with very simple appearance features, the proposed method achieves state-of-the-art performance on standard datasets.
The reaction of n-butyl-lithium with pentachloropyridine: a solvent effect (1967)

J. D. Cook, B. J. Wakefield and C. J. Clayton, Chem. Commun. (London), 1967, 150 DOI: 10.1039/C19670000150
A Computational Modeling Approach for Deriving Biomarkers to Predict Cancer Risk in Premalignant Disease (2016)

The lack of effective biomarkers for predicting cancer risk in premalignant disease is a major clinical problem. There is a near-limitless list of candidate biomarkers, and it remains unclear how best to sample the tissue in space and time. Practical constraints mean that only a few of these candidate biomarker strategies can be evaluated empirically, and there is no framework to determine which of the plethora of possibilities is the most promising. Here, we have sought to solve this problem by developing a theoretical platform for in silico biomarker development. We construct a simple computational model of carcinogenesis in premalignant disease and use the model to evaluate an extensive list of tissue sampling strategies and different molecular measures of these samples. Our model predicts that (i) taking more biopsies improves prognostication, but with diminishing returns for each additional biopsy; (ii) longitudinally collected biopsies provide slightly more prognostic information than a single biopsy collected at the latest possible time point; (iii) measurements of clonal diversity are more prognostic than measurements of the presence or absence of a particular abnormality and are particularly robust to confounding by tissue sampling; and (iv) the spatial pattern of clonal expansions is a particularly prognostic measure. This study demonstrates how the use of a mechanistic framework provided by computational modeling can diminish empirical constraints on biomarker development.