gebhart/patrepeval huggingface dataset:
Stem cell plasticity, cell fusion, and transdifferentiation (2003)

One of the most contentious issues in biology today concerns the existence of stem cell plasticity. The term "plasticity" refers to the capacity of tissue-derived stem cells to exhibit a phenotypic potential that extends beyond the differentiated cell phenotypes of their resident tissue. Although evidence of stem cell plasticity has been reported by multiple laboratories, other scientists have not found the data persuasive and have remained skeptical about these new findings. This review will provide an overview of the stem cell plasticity controversy. We will examine many of the major objections that have been made to challenge the stem cell plasticity data. This controversy will be placed in the context of the traditional view of stem cell potential and cell phenotypic diversification. What the implications of cell plasticity are, and how its existence may modulate our present understanding of stem cell biology, will be explored. In addition, we will examine a topic that is usually not included within a discussion of stem cell biology--the direct conversion of one differentiated cell type into another. We believe that these observations on the transdifferentiation of differentiated cells have direct bearing on the issue of stem cell plasticity, and may provide insights into how cell phenotypic diversification is realized in the adult and into the origin of cell phenotypes during evolution.
HMM based online hand-drawn graphic symbol recognition (2003)

In this paper, an online hand-drawn graphic symbol recognition algorithm based on hidden Markov models is presented. A rearrangement strategy is applied to the hand-drawn symbol points in order to alleviate the influence of the difference in drawing sequence. Based on rearranged drawing points, global distance measure and local angle feature are extracted as the feature vector. After the quantization, a discrete HMM is used as the core recognizer. The experiment shows the recognition rate of our system can be above 85%.
Chemistry in Microstructured Reactors (2004)

The application of microstructured reactors in the chemical process industry has gained significant importance in recent years. Companies that offer not only microstructured reactors, but also entire chemical process plants and services relating to them, are already in existence. In addition, many institutes and universities are active within this field, and process-engineering-oriented reviews and a specialized book are available. Microstructured systems can be applied with particular success in the investigation of highly exothermic and fast reactions. Often the presence of temperature-induced side reactions can be significantly reduced through isothermal operations. Although microstructured reaction techniques have been shown to optimize many synthetic procedures, they have not yet received the attention they deserve in organic chemistry. For this reason, this Review aims to address this by providing an overview of the chemistry in microstructured reactors, grouped into liquid-phase, gas-phase, and gas-liquid reactions.
Characterization of Sorting Signals in the β-Amyloid Precursor Protein Cytoplasmic Domain (1995)

The beta-amyloid precursor protein (APP) is proteolytically processed to generate beta-amyloid protein, the principal protein component of neuropathological lesions characteristic of Alzheimer's disease. To investigate potential sorting signals in the cytoplasmic tail of APP, we transplanted APP cytoplasmic tail sequences into the cytoplasmic tail of the human transferrin receptor (TR) and showed that two sequence motifs from the APP cytoplasmic tail promote TR internalization. One sequence, GYENPTY, is related to the low density lipoprotein receptor internalization signal, FDNPVY, but also involves a critical glycine residue; the other, YTSI, conforms to the 4-residue tyrosine-based internalization signal consensus sequence. Furthermore, a chimeric molecule (APP-TR) consisting of the cytoplasmic domain of APP and the transmembrane and external domains of TR was rapidly internalized enabling the transport of iron into the cell at approximately 50% the rate of wild-type TR. Alanine scanning mutations indicated that the two sequences identified in transplantation experiments were required for internalization of the chimera. Metabolic pulse-chase experiments showed that the APP-TR chimeras were degraded in a post-Golgi membrane compartment within 2-4 h following normal glycosylation. Degradation was partially dependent upon the two internalization signals and was inhibited by ammonium chloride. A fraction of APP-TR chimeras traffic to a degradative endocytic compartment after appearing on the cell surface. Comparison of soluble APP released from cells expressing either full-length human APP or mutant APP with the sequence YENPTY deleted indicated that this sequence is required for sorting of full-length APP along similar trafficking pathways as the APP-TR chimera.
Pharmacological targeting of the KIT growth factor receptor: a therapeutic consideration for mast cell disorders (2008)

KIT is a member of the tyrosine kinase family of growth factor receptors which is expressed on a variety of haematopoietic cells including mast cells. Stem cell factor (SCF)-dependent activation of KIT is critical for mast cell homeostasis and function. However, when KIT is inappropriately activated, accumulation of mast cells in tissues results in mastocytosis. Such dysregulated KIT activation is a manifestation of specific activating point mutations within KIT, with the human D816V mutation considered as a hallmark of human systemic mastocytosis. A number of other activating mutations in KIT have recently been identified and these mutations may also contribute to aberrant mast cell growth. In addition to its role in mast cell growth, differentiation and survival, localized concentration gradients of SCF may control the targeting of mast cells to specific tissues and, once resident within these tissues, mast cell activation by antigen may also be amplified by SCF. Thus, KIT inhibitors may have potential application in multiple conditions linked to mast cells including systemic mastocytosis, anaphylaxis, and asthma. In this review, we discuss the role of KIT in the context of mast cells in these disease states and how recent advances in the development of inhibitors of KIT activity and function may offer novel therapies for the treatment of these disorders.
The pre-stack image map of subface seismic data in the horizontal time-vertical time domain (1992)

One of the goals of seismic data processing is to produce a section that in some way may be regarded as a subsurface cross section. The normal processing route includes NMO, CMP stacking and imaging in a post-stack migration procedure. This proces works well on areas with uniform dip. However when the stacking velocities are dip-dependent the final image will be degraded.
Successful Asfotase Alfa Treatment in an Adult Dialysis Patient With Childhood-Onset Hypophosphatasia (2017)

Hypophosphatasia is an inherited disease characterized by reduced alkaline phosphatase activity, extracellular accumulation of inorganic pyrophosphate, and impaired bone mineralization. Asfotase alfa (AA) is a recombinant human alkaline phosphatase therapy approved for treatment of pediatric-onset hypophosphatasia. Studies show promising outcome in AA-treated children with hypophosphatasia; however, data on adults with pediatric-onset hypophosphatasia are scarce. We report on a 59-year-old woman with childhood-onset hypophosphatasia and a history of multiple fractures and orthopedic procedures. Owing to renal failure (histological diagnosis: focal segmental glomerulosclerosis), hemodialysis was started in 2013. By the end of 2015, the patient was unable to walk, could only stand for 30 seconds, and was completely dependent on help for activities of daily living. After 13 months of AA therapy, the patient showed a dramatic increase in quality of life (increased mobility), reduction in pain medication, and a significant improvement in bone mineralization throughout the skeleton, including consolidation of existing fractures and no occurrence of new fractures. This case report demonstrates a relevant therapeutic success of AA treatment in an adult hemodialysis patient with childhood onset of hypophosphatasia.
Multi-task feature and kernel selection for SVMs (2004)

We compute a common feature selection or kernel selection configuration for multiple support vector machines (SVMs) trained on different yet inter-related datasets. The method is advantageous when multiple classification tasks and differently labeled datasets exist over a common input space. Different datasets can mutually reinforce a common choice of representation or relevant features for their various classifiers. We derive a multi-task representation learning approach using the maximum entropy discrimination formalism. The resulting convex algorithms maintain the global solution properties of support vector machines. However, in addition to multiple SVM classification/regression parameters they also jointly estimate an optimal subset of features or optimal combination of kernels. Experiments are shown on standardized datasets.
A hypertext system to manage software life cycle documents (2003)

A description is given of the DIF documents integration facility, a hypertext system that helps integrate and manage the documents produced and used throughout the life cycle of software projects. it was designed for use in the System Factory, a six-year-old experimental laboratory project at USC to study the development, use, and maintenance of software systems. DIF provides an interface to a hypertext-based information storage structure and to a structured documentation process, A hypertext of software information is built by the software engineers over eight life cycle activities. Salient aspects of DIF include integration of documents within and across several projects, facilities for browsing a hypertext of software documents, support for parallel development of documents, interface to various software-engineering tools, and facilitation of document reuse.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
"Nano": The new nemesis of cancer (2006)

Materials at nano dimensions exhibit totally different properties compared to their bulk and atomic states. This feature has been harnessed by scientists from various disciplines, to develop functional nanomaterials for cancer diagnosis and therapeutics. The success stories range from delivering chemotherapeutic molecules in nano-sized formulations to functional nanomaterials, which deliver thermal and radiotherapy at specific targeted sites. This brief review summarizes the recent developments of various nanotechnologies in cancer therapy and diagnostics, both from the research sector and the upcoming products in pipeline on its route to commercialization. Supportive engineering innovations and frontiers in nanomolecular research, with a potential to revolutionize cancer therapy, have been discussed in brief.
National assessments : testing the system (1996)

This book is concerned with educational assessments that are systematic, usually sample based, collections of data that include a measurement of student achievement to guide policy. The book is organized into four parts. Part 1 develops the framework for placing national assessments in the context of various testing purposes, examines the origins of educational assessments, and describes national assessments, including their purposes and characteristics. It concludes by looking at the uses of data from public examinations for educational assessment. Part 2 is concerned with the stages in establishing national assessment systems, their costs, and the development of the test formats required. Part 3 provides five country case studies of national assessment systems. The countries studied are Chile, Colombia, Egypt, England and Wales, and Thailand. The book concludes with a review of the lessons learned from these five studies.
Accurate Genome Relative Abundance Estimation Based on Shotgun Metagenomic Reads (2011)

Accurate estimation of microbial community composition based on metagenomic sequencing data is fundamental for subsequent metagenomics analysis. Prevalent estimation methods are mainly based on directly summarizing alignment results or its variants; often result in biased and/or unstable estimates. We have developed a unified probabilistic framework (named GRAMMy) by explicitly modeling read assignment ambiguities, genome size biases and read distributions along the genomes. Maximum likelihood method is employed to compute Genome Relative Abundance of microbial communities using the Mixture Model theory (GRAMMy). GRAMMy has been demonstrated to give estimates that are accurate and robust across both simulated and real read benchmark datasets. We applied GRAMMy to a collection of 34 metagenomic read sets from four metagenomics projects and identified 99 frequent species (minimally 0.5% abundant in at least 50% of the data-sets) in the human gut samples. Our results show substantial improvements over previous studies, such as adjusting the over-estimated abundance for Bacteroides species for human gut samples, by providing a new reference-based strategy for metagenomic sample comparisons. GRAMMy can be used flexibly with many read assignment tools (mapping, alignment or composition-based) even with low-sensitivity mapping results from huge short-read datasets. It will be increasingly useful as an accurate and robust tool for abundance estimation with the growing size of read sets and the expanding database of reference genomes.
Direct Web switch routing with state migration, TCP masquerade, and cookie name rewriting (2004)

Existing layer 4 load balancers are content-blind and often have difficulty in redirecting HTTP requests to the appropriate server in the session manner. Layer 7 load balancers, also referred to as Web switches, are content-aware and support session persistence. However, most Web switches employ a bidirectional architecture, which means that request and response traffic must both pass through the load balancer. This means a Web switch can easily become a bottleneck. We present a direct routing architecture to prevent response traffic from passing through the Web switch. Our solution is highly scalable in the number of back-end servers. In addition, two simple but effective mechanisms, one-packet TCP state migration and cookie name rewriting to packet filter, are presented to support persistent connection and session persistence. Through the external benchmark, we prove that our system outperforms existing solutions. The internal benchmark investigates the bottlenecks of our system and suggests areas for future improvement.
Resonant tunneling circuit technology: has it arrived? (2002)

A three-dimensional large-scale integration (LSI) process for fabrication of resonant tunneling diodes and heterojunction field-effect transistors on InP has been demonstrated, combining two of today's fastest semiconductor devices. Demonstrations of this technology now include multigigahertz digital and mixed-signal circuits and ultralow power SRAM circuits; 25 to 100 GHz circuits are clearly in range for this technology.
Spatial distribution and abundance of larval and juvenile fish, chlorophyll and macrozooplankton around the Mississippi River discharge plume, and the role of the plume in fish recruitment (1991)

In September 1986, we collected neuston (1 x 2 m, 0.947 mm mesh) and surface chlorophyll a samples and hydrographic data at 46 stations around the discharge plume of the Mississippi River. Transects were positioned so that the 3 water masses in the plume areaplume water, Gulf of Mexico shelf water and frontal water (a mixture of the former 2)were sampled. The plume was represented by a shallow lens of water < 3 4 '10 salinity and < 29 "C resting atop warmer (> 29 "C) and more saline (> 34 %) Gulf of Mexico shelf water. Strong turbidity fronts with a scale of 50 to 100 m form, relax and reform approximately at tidal frequencies within the frontal region that has a larger scale of 6 to 8 km. Total ichthyoplankton catch per tow, individual surface chlorophyll a values and macrozooplankton displacement volumes were all significantly greater in frontal waters than adjacent Gulf of Mexico shelf or plume waters Hydrodynamic convergence at the continually forming and relaxing turbidity fronts most likely accounts for concentrated neustonic ichthyoplankton, and at least partially for high macrozooplankton values as well, in frontal waters. Elevated macrozooplankton displacement volumes in frontal waters may also result from higher rates of proliferation of macrozooplankton biomass. High primary production in frontal water is probably due to the mixing of nutrientrich, but turbid, plume water (where photosynthesis is light limited) with clear, but nutrient-poor, Gulf of Mexico shelf water (where photosynthesis is nutrient limited) creating favorable phytoplankton growth conditions. Concentrations of ichthyoplankton and zooplankton offer rich trophic resources that some species utilize to gain superior growth. Faster growth will lead to increased survival and recruitment (because larvae pass through the period of greatest vulnerability to predation by gapelimited predators more quickly) if larval growth is increased disportionately to larval mortality from predation.
Comparison of the Troponin T and Troponin I ELISA Tests, as Measured by Microplate Immunoassay Techniques, in Diagnosing Acute Myocardial Infarction (1997)

We describe an improved procedure using a standard microplate immunoassay reader to measure the concentration of troponin T in human serum. We also describe an immunoassay for troponin I in serum. Only 160 microliters of serum are needed for a single analysis of each troponin. For comparison, creatine kinase MB mass analysis in serum was performed with a commercial luminometric method. From 95 apparently healthy people the following values were obtained: creatine kinase MB mass 2.6 +/- 1.2 micrograms/l, troponin T 0.027 +/- 0.025 microgram/l and troponin I 0.03 +/- 0.031 microgram/l. We compared the results of troponin T and troponin I methods with each other, as well as with those of creatine kinase MB mass measured in 48 patients with verified acute myocardial infarction and in 60 control patients with non-cardiac chest pain. The correlation between troponin T and troponin I values was 0.91 for the total material and 0.94 for 48 patients with acute myocardial infarction. Troponin I showed better earlier sensitivity than troponin T (p = 0.043). In nine patients in the control group, creatine kinase MB mass exceeded the reference limit of 5.0 micrograms/l, while in two patients the cut-off limit of 10.0 micrograms/l was also surpassed, pointing to non-specificity. In the group of infarct patients, the highest serum creatinine value was 193 mumol/l, whereas in the control group it was 406 mumol/l. The sera of patients with impaired renal function without any cardiac failure showed no increase in troponin T and troponin I values. In conclusion, serum creatine kinase MB mass and troponin I seem to confirm an acute myocardial infarction more rapidly than does troponin T; troponin I has the highest cardiac specificity.
Inhibition of Ras-Induced DNA Synthesis by Expression of the Phosphatase MKP-1 (1994)

Mitogen-activated protein kinases (MAP kinases) are common components of signaling pathways induced by diverse growth stimuli. Although the guanidine nucleotide-binding Ras proteins are known to be upstream activators of MAP kinases, the extent to which MAP kinases directly contribute to the mitogenic effect of Ras is as yet undefined. In this study, inhibition of MAP kinases by the MAP kinase phosphatase MKP-1 blocked the induction of DNA synthesis in quiescent rat embryonic fibroblast REF-52 cells by an activated mutant of Ras, V12Ras. These results suggest an essential role for activation of MAP kinases in the transition from the quiescent to the DNA replication phase of the eukaryotic cell cycle.
Preclinical Characterization of Recombinant Human Tissue Kallikrein-1 as a Novel Treatment for Type 2 Diabetes Mellitus (2014)

Modulation of the kallikrein-kinin system (KKS) has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D). The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the protease that generates bradykinin in situ, is much less understood. We developed and tested DM199, recombinant human tissue kallikrein-1 protein (rhKLK-1), as a potential novel therapeutic for T2D. Hyperinsulinemic-euglycemic clamp studies suggest that DM199 increases whole body glucose disposal in non-diabetic rats. Single-dose administration of DM199 in obese db/db mice and ZDF rats, showed an acute, dose-dependent improvement in whole-body glucose utilization. Sub-acute dosing for a week in ZDF rats improved glucose utilization, with a concomitant rise in fasting insulin levels and HOMA1-%B scores. After cessation of sub-acute dosing, fasting blood glucose levels were significantly lower in ZDF rats during a drug wash-out period. Our studies show for the first time that DM199 administration results in acute anti-hyperglycemic effects in several preclinical models, and demonstrate the potential for further development of DM199 as a novel therapeutic for T2D.
Directed evolution of the transcription factor XylS for development of improved expression systems (2009)

The inducible Pm promoter together with its cognate positive transcription regulator XylS has been shown to be useful for recombinant protein production under high cell density conditions. Here we report directed evolution of XylS resulting in mutant proteins with increased ability to stimulate transcription in Escherichia coli from Pm. A first round of mutagenesis using error-prone PCR on xylS was used to construct a library consisting of about 430,000 clones, and this library could be efficiently screened with respect to stimulation of expression from Pm due to a positive correlation between the level of expression of the reporter gene, bla (encoding β-lactamase), and the ampicillin tolerance of the corresponding host cells. Fourteen different amino acid substitutions in XylS were found to separately lead to up to nearly a threefold stimulation of expression under induced conditions, relative to wild type. These mutations were all located in the part corresponding to the N-terminal half of the protein. Varying combinations of the mutations resulted in further stimulation, and the best results (about 10-fold stimulation under induced conditions) were obtained by using a random shuffling procedure followed by a new round of screening. The uninduced levels of expression for the same mutants also increased, but only about four times. Through in silico 3D modelling of the N-terminal domain of XylS, it was observed that the evolved mutant proteins contained substitutions that were positioned in different parts of the predicted structure, including a β-barrel putatively responsible for effector binding and a coiled coil probably important for dimerization. The total production of the host-toxic antibody fragment scFv-phOx expressed from Pm with the evolved XylS mutant protein StEP-13 was about ninefold higher than with wild-type XylS, demonstrating that directed evolution of transcription factors can be an important new tool to achieve high-level recombinant protein production.