gebhart/patrepeval huggingface dataset:
TGF-α Mediates Genetic Susceptibility to Chronic Kidney Disease (2010)

The mechanisms of progression of chronic kidney disease (CKD) are poorly understood. Epidemiologic studies suggest a strong genetic component, but the genes that contribute to the onset and progression of CKD are largely unknown. Here, we applied an experimental model of CKD (75% excision of total renal mass) to six different strains of mice and found that only the FVB/N strain developed renal lesions. We performed a genome-scan analysis in mice generated by back-crossing resistant and sensitive strains; we identified a major susceptibility locus (Ckdp1) on chromosome 6, which corresponds to regions on human chromosome 2 and 3 that link with CKD progression. In silico analysis revealed that the locus includes the gene encoding the EGF receptor (EGFR) ligand TGF-α. TGF-α protein levels markedly increased after nephron reduction exclusively in FVB/N mice, and this increase preceded the development of renal lesions. Furthermore, pharmacologic inhibition of EGFR prevented the development of renal lesions in the sensitive FVB/N strain. These data suggest that variable TGF-α expression may explain, in part, the genetic susceptibility to CKD progression. EGFR inhibition may be a therapeutic strategy to counteract the genetic predisposition to CKD.
Expression of functional recombinant human procathepsin B in mammalian cells (1996)

Cathepsin B has been implicated in numerous pathobiological processes. In order to study its interactions with other proteins implicated in these processes, quantities of functional recombinant cathepsin B are needed. Therefore, we expressed recombinant human procathepsin B in mammalian cells (BSC-1 monkey kidney cells and HeLa human cervical carcinoma cells) using a vaccinia virus expression system. The recombinant human procathepsin B appeared to be authentic and expressed in its native conformation as indicated by: (1) N-terminal sequencing; (2) molecular size; (3) processing intracellularly to mature double-chain cathepsin B; (4) in vitro cleavage by pepsin to mature cathepsin B coincident with appearance of activity against a selective synthetic substrate; and (5) substrate/inhibitor profiles. This is the first report of the expression of functional recombinant human procathepsin B in mammalian cells. We also report a single-step immunoaffinity purification procedure for the isolation of electrophoretically pure proenzyme. By the methodologies described, human procathepsin B can now be obtained in high yield. This should facilitate studies of its interactions with protease inhibitors, other proteases, extracellular matrices, cell-surface proteins and biological substrates that may be of relevance to the pathobiological functions of this enzyme.
Automated GUI Test Coverage Analysis Using GA (2010)

A Graphical User Interface (GUI) is a graphical front-end to a software system. A GUI contains graphical objects with certain distinct values which can be used to determine the state of the GUI at any time. Software developing organizations always desire to test the software thoroughly to get maximum confidence about its quality. But this requires gigantic effort to test a GUI application due to the complexity involved in such applications. This problem has led to the automation of GUI testing and different techniques have been proposed for automated GUI Testing. Event-flow graph is a fresh technique being used in the field of automated GUI testing. Just as control-flow graph, another GUI model that represents all possible execution paths in a program, event-flow model, in the same way, represents all promising progressions of events that can be executed on the GUI. Another challenging question in software testing is, “How much testing is enough?” As development proceeds, there are fewer measures available that can be used to provide guidance on the quality of an automatic test suite. Genetic algorithm searches for the best possible test parameter combinations that are according to some predefined test criterion. Usually this test criterion corresponds to a “coverage function” that measures how much of the automatically generated optimization parameters satisfies the given test criterion. In this paper, we have attempted to exploit the event driven nature of GUI. Based on this nature, we have presented a GUI testing and coverage analysis technique centered on genetic algorithms.
Ablation of the CDK inhibitor p57Kip2 results in increased apoptosis and delayed differentiation during mouse development. (1997)

p57(Kip2) is a paternally imprinted gene that encodes a potent inhibitor of several cyclin/Cdk complexes. p57(Kip2) is primarily expressed in terminally differentiated cells, associates with G1 Cdks, and can cause cell cycle arrest in G1 phase. To investigate the role of p57(Kip2) in vivo, we have ablated the p57(Kip2) gene by homologous recombination in ES cells and generated mice devoid of p57(Kip2) expression. Most p57(Kip2) null mice die after birth and display severe developmental defects with varying degrees of penetrance. As expected, heterozygous mice that inherit a maternal, but not a paternal, targeted allele exhibit similar deficiencies and neonatal death. Developmental defects of p57(Kip2) mutant mice include cleft palate and gastrointestinal abnormalities ranging from an inflated GI tract to loss of the jejunum and ileum. These tissues display a significant increase of apoptotic cells in the absence of p57(Kip2). Most p57(Kip2) mutant mice have short limbs, a defect attributable to abnormal endochondral ossification caused by delayed cell cycle exit during chondrocyte differentiation. A similar defect has been observed in mice lacking p107 and p130, thus suggesting that p57(Kip2) might be an upstream regulator of these Rb-related proteins. The p57(Kip2) locus has been implicated in the Beckwith-Wiedemann syndrome and in the development of sporadic Wilms' tumors and lung carcinomas. To date, we have not observed neoplastic development even in those p57(Kip2) mutant mice that have survived for >5 months of age. These findings indicate that p57(Kip2) has an important role during mouse development that cannot be compensated by other Cdk inhibitors.
An application of belief networks to future crop production (2002)

Bayesian belief networks are shown to be natural and efficient knowledge representation tools for modelling and manipulating uncertainties in developing expert systems. They provide a basis for probabilistic inference, to calculate the changes in probabilistic belief as new evidence is obtained. However, their use in real problem domains is hampered by the difficulties facing the construction of such belief networks, particularly in domains where neither sufficient data nor human expertise is available. In this paper, we show that this problem can be circumvented by exploiting knowledge from existing mathematical models. An application of belief networks to assess the impact of climate change on potato production is used as an illustration. We show how the uncertainty of future climate change, variability of current weather and the knowledge about potato development can be combined in a belief network, which provides an aid for policy makers in agriculture. The model is tested using synthetic weather scenarios. The results are compared with those obtained from a conventional mathematical model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Maximum Entropy Aggregation of Expert Predictions (1996)

This paper presents a maximum entropy framework for the aggregation of expert opinions where the expert opinions concern the prediction of the outcome of an uncertain event. The event to be predicted and individual predictions rendered are assumed to be discrete random variables. A measure of expert competence is defined using a distance metric between the actual outcome of the event and each expert's predicted outcome. Following Levy and Delic (Levy, W. B., H. Delic. 1994. Maximum entropy aggregation of individual opinions. IEEE Trans. Sys. Man & Cybernetics 24 606–613.), we use Shannon's information measure (Shannon [Shannon, C. E. 1948. A mathematical theory of communication. Bell Syst. Tech. J. 27 379–423.], Jaynes [Jaynes, E. T. 1957. Information theory and statistical mechanics. Phys. Rev. 106 Part I: 620–630, 108 Part II: 171–190.]) to derive aggregation rules for combining two or more expert predictions into a single aggregated prediction that appropriately calibrates different degrees of expert competence and reflects any dependence that may exist among the expert predictions. The resulting maximum entropy aggregated prediction is least prejudiced in the sense that it utilizes all information available but remains maximally non committal with regard to information not available. Numerical examples to illuminate the implications of maximum entropy aggregation are also presented.
Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast cancer cells: implications for tumour–stroma interactions (2006)

Our previous investigations using cell models of tamoxifen resistance have shown that the acquisition of an endocrine-insensitive state is accompanied by an invasive in vitro phenotype. In this study, we wished to determine whether this was specifically related to partial oestrogen receptor agonists or whether similar phenomena arise with the newer 'pure' anti-oestrogens, exemplified by fulvestrant. Our data demonstrate that the development of fulvestrant resistance in two breast cancer cell lines, MCF7 and T47D, is accompanied by an augmented migratory and invasive phenotype in vitro and overexpression of the HGF/SF receptor, c-Met. Importantly, upregulated c-Met expression in these cells facilitates their stimulation by HGF/SF-secreting stromal fibroblasts, leading to the activation of Src, Akt and ERK1/2 and a profound enhancement of their aggressive phenotype in vitro. These effects could be specifically attributable to activation of the c-Met receptor since the inclusion of neutralising antibodies to c-Met, or siRNA-mediated knockdown of c-Met expression, suppressed both invasion and migration stimulated by either exogenous HGF/SF, fibroblast-conditioned medium or following co-culture with fibroblast cells. Together, these in vitro data suggest that the development of fulvestrant resistance in vivo may confer a metastatic advantage to the cells by allowing their migratory and invasive behaviour to be augmented by surrounding stromal cells.
Variability in individual serum cholesterol response to change in diet. (1983)

Few systematic data are available on the range of individual blood lipid responsiveness to specific diet changes. Multiple, carefully standardized total serum cholesterol (TC) measurements were made in 58 men under a variety of controlled dietary conditions. Responsiveness was defined for each individual as the change in mean TC per unit change in Diet Score based on the Keys-Minnesota equation. Only 3% were potentially "nonresponders," and even these probably evidenced some response. Of the group, 64% responded within 30% of prediction. We classed 9% as hyporesponders, while in another 9% responsiveness exceeded 1.5 times expectation. We conclude that in metabolically normal individuals the variation in short-term response to dietary change is normally distributed but that nonresponse to diet change is rare. Because metabolic, intrinsic hyporesponsiveness of TC to change in diet composition is uncommon, assessment of the real effectiveness of a dietary regimen in an individual is best based on observed dietary changes. TC changes among individuals under treatment should be based on multiple determinations and interpreted with caution.
Adipose tissue density, estimated adipose lipid fraction and whole body adiposity in male cadavers. (1994)

Lipid and water together typically make up more than 90% of the body's adipose tissue mass. Although some reports have shown that the fraction of lipid in adipose tissue is greater in obese people than in lean ones, the quantitative relationship between adipose lipid fraction and overall adiposity of the body has never been investigated. We dissected six male unembalmed cadavers and weighed all adipose tissue (range 9.7-25.7 kg), allowing the calculation of percentage adiposity as 100 x total adipose mass/body mass (range 17.8-43.9%). Adipose tissue volume was determined by hydrostatic weighing of all portions of the dissected adipose tissue. For the six cadavers, whole body adipose tissue density ranged from 0.925-0.970 g/ml. Based on a three-component model of adipose tissue (lipid, water and dry fat-free solids), an expression for lipid fraction, F, was derived. After assuming densities for adipose lipid (0.905 g/ml), water at 36 degrees C (0.997 g/ml) and the dry fat-free component (1.38 g/ml), the equation simplified to F = 6.256/D-5.912, where D is adipose tissue density (g/ml). Lipid fraction was then calculated for each of the six cadavers: the range (0.54-0.85) was in excellent agreement with published data. There was a significant correlation (r = 0.95, P < 0.005) between calculated lipid fraction and percentage adiposity. The regression equation predicting lipid fraction from percentage adiposity was y = 0.327 + 0.0124x. We conclude that the estimated fraction of lipid in human adipose tissue shows both a wide range and a strong positive linear relationship with overall body fatness.
The potential of fire assay and inductively coupled plasma source mass spectrometry for the determination of platinum group elements in geological materials (1987)

Preliminary work on the application of fire assay and inductively coupled plasma source mass spectrometry (ICP-MS) to the determination of platinum-group elements (PGEs) in geological materials is described. A combination of the neo-classical nickel sulphide fire assay collection procedure with final determination by ICP-MS is considered in relation to the simplified procedure required for dissolution of the nickel sulphide “button” and the wealth of information inherent in ICP-MS spectra. The method was applied to the determination of five PGEs and gold in the South African standard reference material PTO-1 (now known as SARM-7) and the Canadian standard reference material PTC-1. Isotope dilution analysis was applied to the determination of platinum.
Reaction kinetics for chemical engineers (1959)

Fundamentals homogeneous isothermal reactions adiabatic and programmed reactions continuous stirred reactors homogeneous flow reactions uncatalyzed heterogeneous reactions fluid-phase reactions catalyzed by solids fixed and fluidized beds of particles heterogeneous catalysis scaling up test results industrial reactors mathematics for review. Appendices: the literature of reaction kinetics constants and conversion factors.
A framework for the<i>in vitro</i>evaluation of cancer-relevant molecular characteristics and mitogenic potency of insulin analogues (2015)

Epidemiological and laboratory studies raise the possibility of a link between clinically prescribed insulin analogues and increased cancer risk. Accordingly, there is a regulatory mandate for cancer-related pre-clinical safety evaluation during insulin analogue development, but currently, there is no standardized framework for such in vitro evaluation. We tested human insulin; the super-mitogenic insulin, X10 and insulin-like growth factor I, in four cancer cell lines with a range of insulin-like growth factor-I receptor (IGF-IR)/IR (insulin receptor) ratios (HCT 116, HT-29, COLO 205 and MCF7) and related these to IGF-IR and IR expression in 17 human adenocarcinomas. All cell types were IR-A isoform dominant. We determined IGF-IR/IR signalling pathway endpoints in dose- and time-varying experiments, and performed mitogenic dose-response equivalent assays to derive EC50 values, and correlated these with IGF-IR/IR ratios. We superimposed relative EC50 values onto data from the literature in a meta-analysis. The IGF-IR/IR ratios varied from <1 to 12 in the selected cell lines; similar pattern ranges were observed in human adenocarcinomas. The three ligands demonstrated differential IR/IGF-IR and Akt phosphorylation, which correlated with cell-specific IGF-IR/IR ratios. Mitogenic profiles of X10 mimicked those for insulin-like growth factor I (IGF-I) and correlated with IGF-IR/IR ratios. The meta-analysis, adding data from five additional studies, supported the hypothesis that ligand mitogenic potency, relative to human insulin, increases with increasing cell-specific IGF-IR/IR ratio. This study established a framework for the in vitro evaluation of cancer-relevant bioassays for comparisons of insulin analogues, and specifically consolidated earlier studies that determination of the cell-specific IGF-IR/IR ratio is crucial for the interpretation of ranking relative biological activities.
Hall Effect Devices (1989)

After a short introduction to the operating principle and the basic characteristics of Hall devices, the most interesting recent advances in the field are reviewed. They include: better understanding of the influence of device geometry on sensor characteristics; results of research into parasitic and second-order effects, such as the piezo-Hall effect, non-linearity effects and surface effects, the last affecting device sensitivity, 1/f noise and offset; new designs and technologies, yielding buried Hall devices, vertical Hall devices and two-dimensional electron gas Hall devices; and new electronic methods for the improvement of sensor characteristics, such as correction of non-linearity effects and offset reduction.
The yeast nuclear gene suv3 affecting mitochondrial post-transcriptional processes encodes a putative ATP-dependent RNA helicase. (1992)

Mitochondrial gene expression is controlled largely through the action of products of the nuclear genome. The yeast nuclear gene suv3 has been implicated in a variety of mitochondrial posttranscriptional processes and in translation and, thus, represents a key control element in nuclear-mitochondrial interactions. We have exploited a property of a mutant allele of suv3, SUV3-1, that causes, among other effects, a massive increase in the abundance of excised group I introns to clone the wild-type gene by a strategy of colony Northern hybridization. We have determined that the 84-kDa deduced protein product of the suv3 gene, which maps to chromosome XVI, has a typical mitochondrial targeting presequence and additional sequence motifs that suggest that it belongs to a family of ATP-dependent RNA helicases, enzymes whose importance in post-transcriptional and translational events has recently become apparent. We have identified the SUV3-1 mutation as a G----T transversion that creates a Val----Leu substitution in a 10-amino acid block that is highly conserved among ATP-dependent RNA helicases. We discuss some implications of this mutation on the effects of the SUV3-1 allele on mitochondrial RNA metabolism.
Computation of Unsteady Nonlinear Flows in Cascades Using a Harmonic Balance Technique (2002)

A harmonic balance technique for modeling unsteady nonlinear e ows in turbomachinery is presented. The analysis exploits the fact that many unsteady e ows of interest in turbomachinery are periodic in time. Thus, the unsteady e ow conservation variables may be represented by a Fourier series in time with spatially varying coefe cients. This assumption leads to a harmonic balance form of the Euler or Navier ‐Stokes equations, which, in turn, can be solved efe ciently as a steady problem using conventional computational e uid dynamic (CFD) methods, including pseudotime time marching with local time stepping and multigrid acceleration. Thus, the method is computationally efe cient, at least one to two orders of magnitude faster than conventional nonlinear time-domain CFD simulations. Computational results for unsteady, transonic, viscous e ow in the front stage rotor of a high-pressure compressor demonstrate that even strongly nonlinear e ows can be modeled to engineering accuracy with a small number of terms retained in the Fourier series representation of the e ow. Furthermore, in some cases, e uid nonlinearities are found to be important for surprisingly small blade vibrations.
Ensuring compatible interactions within component-based software systems (2004)

The interface definition of a component in a distributed system forms the contract between the component itself and its neighbouring components regarding the use of its services. In general, such a contract should cover the issues of service functionality, usage and quality. The interface definition languages (IDLs) used by commercial middleware standards such as CORBA primarily address the signature issues of such a contract, i.e., the forms and types of component or object services. Nothing is said about other aspects of the contract, including the way in which the component services are to be used. We introduce a framework and associated techniques that augment commercial IDLs with interaction protocol specifications and validate component interactions against such protocol specifications at run-time. In effect, the validation becomes a useful tool for testing whether or not the object services are used properly in a distributed system. Our approach has been implemented in the CORBA context, but can be readily applied to other IDL-based object/component systems.
Considerations for follow-the-leader motion of extensible tendon-driven continuum robots (2016)

Path following and follow-the-leader motion is particularly desirable for minimally-invasive surgery in confined spaces which can only be reached using tortuous paths, e.g. through natural orifices. While path following and followthe- leader motion can be achieved by hyper-redundant snake robots, their size is usually not applicable for medical applications. Continuum robots, such as tendon-driven or concentric tube mechanisms, fulfill the size requirements for minimally invasive surgery, but yet follow-the-leader motion is not inherently provided. In fact, parameters of the manipulator's section curvatures and translation have to be chosen wisely a priori. In this paper, we consider a tendon-driven continuum robot with extensible sections. After reformulating the forward kinematics model, we formulate prerequisites for follow-the-leader motion and present a general approach to determine a sequence of robot configurations to achieve follow-the-leader motion along a given 3D path. We evaluate our approach in a series of simulations with 3D paths composed of constant curvature arcs and general 3D paths described by B-spline curves. Our results show that mean path errors <;0.4mm and mean tip errors <;1.6mm can theoretically be achieved for constant curvature paths and <;2mm and <;3.1mm for general B-spline curves respectively.