gebhart/patrepeval huggingface dataset:
Different assemblies of Notch receptors coordinate the distribution of the major bronchial Clara, ciliated and neuroendocrine cells (2012)

In the developing lung, it is thought that the terminal buds of elongating airways contain a population of multipotent epithelial progenitors. As the bronchial tree extends, descendants of these cells give rise to lineage-restricted progenitors in the conducting airways via Notch signaling, which is involved in the establishment of epithelial Clara, ciliated and pulmonary neuroendocrine (NE) cell populations. However, the precise molecular details of this selection process are still emerging. Our stepwise removal of the three Notch receptors from the developing lung epithelium reveals that, whereas Notch2 mediates the Clara/ciliated cell fate decision with negligible contributions from Notch1 and Notch3, all three Notch receptors contribute in an additive manner to regulate the abundance of NE cells and the size of the presumptive pulmonary neuroepithelial body (pNEB) as a result of mutual interactions between NE cells and the Notch-dependent, SSEA-1(+), CC10(-) cell population surrounding the pNEB (SPNC cells). Ectopic expression of the Notch1 or Notch2 intracellular domain was sufficient to induce SSEA-1(+) cells and to suppress pNEB formation without expending Clara cells. We provide evidence that the additive functions of Notch receptors, together with other signaling pathways, maintains the expression of Hes1, a key regulator of NE cell fate, and that maintenance of Hes1 expression in epithelial cells is key to the regulation of pNEB size. These results suggest that two different assemblies of Notch receptors coordinate the numbers and distribution of the major epithelial cell types in the conducting airway during lung organogenesis.
The Western Farmer in Imaginative Literature, 1818-1891 (1949)

Journal Article The Western Farmer in Imaginative Literature, 1818–1891 Get access Henry Nash Smith Henry Nash Smith Search for other works by this author on: Oxford Academic Google Scholar Journal of American History, Volume 36, Issue 3, December 1949, Pages 479–490, https://doi.org/10.2307/1893018 Published: 01 December 1949
Small molecule activators of the Trk receptors for neuroprotection (2008)

The neurotrophin signaling network is critical to the development and survival of many neuronal populations. Especially sensitive to imbalances in the neurotrophin system, cholinergic neurons in the basal forebrain are progressively lost in Alzheimer's disease. Therapeutic use of neurotrophins to prevent this loss is hampered, however, by a number of pharmacological challenges. These include a lack of transport across the blood-brain barrier, rapid degradation in the circulation, and difficulty in production. In this review we discuss the evidence supporting the neurotrophin system's role in preventing neurodegeneration and survey some of the pharmacological strategies being pursued to develop effective therapeutics targeting neurotrophin function.
Syntactic Unification Problems under Constrained Substitutions (1997)

... This paper is a collection of results on the decidability and the computational complexity of a syntactic unification problem under constrained substitutions. A number of decidable, undecidable, tractable and intractable results of the problem are presented. Since a unification problem under constrained substitutions can be regarded as an order-sorted unification problem with term declarations such that the number of sorts is only one, the results presented in this paper also indicate how the intractability of order-sorted unification problems is reduced by restricting the number of sorts to one.
A novel architecture for on-chip path delay measurement (2009)

As technology scales to 45nm and below, the deviation between predicted path delay using simulation and actual path delay on a manufactured chip increases. Hence, on-chip measurement architectures are now widely used due to their higher accuracy and lower cost compared to using external expensive testers. In this paper, we propose a novel path delay measurement architecture called Enhanced path-based ring oscillator (Path-RO) that takes into account variations. The proposed Enhanced Path-RO can accurately and quickly measure path delay on-chip under variations with nearly no impact on functional data path. Enhanced Path-RO is perfectly suitable for fast and accurate speed binning as well by targeting speed paths on-chip even in presence of clock skew. Simulation results under variations collected by the Enhanced Path-RO inserted into ITC'99 b19 circuit demonstrate its high accuracy and efficiency.
Analysis of transient gain saturation and recovery in erbium-doped fiber amplifiers (1989)

An analysis of transient gain dynamics in erbium-doped fiber amplifiers is presented to provide a qualitative explanation of its time constants. The theory yields analytical solutions at the fiber amplifier input end, making it convenient to study the time dependence of gain saturation and recovery under changing input signal conditions. It is shown that, independently of the pump wavelength, gain saturation and recovery effects have long characteristic times (0.2-10.0 ms) which advantageously reduce saturation-induced crosstalk in the amplifier. The effect of saturation-induced gain modulation is found to vanish at signal frequencies above F=1 kHz, which is in good agreement with observed experimental results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS (2014)

BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.
Control of Genotoxic Impurities in Active Pharmaceutical Ingredients: A Review and Perspective (2010)

Recent guidelines from drug regulatory authorities in Europe and the Untited States of America (USA) require the control of genotoxic and potentially genotoxic impurities at parts per million levels in drug substances. This review will discuss the background to the guidelines and the various strategies drug substance manufacturers have employed to comply with the very tight constraints. These strategies include (a) redesigning the drug substance synthesis to avoid introducing problematic impurities, (b) altering relevant process parameters to remove or reduce such impurities to insignificant levels, (c) deploying process understanding to prove that a particular genotoxic impurity either cannot be formed or will be efficiently removed, (d) conducting toxicity studies to demonstrate that a suspect impurity is not harmful at the low levels envisaged for it. Examples of each approach are given.
Evaluation of three methods for DNA fingerprinting of Corynebacterium pseudotuberculosis strains isolated from goats in Poland. (2008)

Phenotypic approaches based on metabolic and biological characteristics of Corynebacterium pseudotuberculosis have been limited due to insufficient discrimination between closely related isolates. In this paper we present performance and convenience of three molecular typing methods: BOX-PCR, random amplification of polymorphic DNA (RAPD) and amplification of DNA fragments surrounding rare restriction site (ADSRRS-fingerprinting) in genome analysis of these bacteria. Among examined 61 strains there were distinguished four, eight and 10 different genotypes by BOX-PCR, RAPD and ADSRRS-fingerprinting, respectively. The value of discrimination index was the lowest for BOX-PCR (D = 0.265), much bigger for RAPD (D = 0.539) and the highest for ADSRRS-fingerprinting (D = 0.604). The good discriminatory ability and reproducibility of RAPD and ADSRRS-fingerprinting indicates that those techniques may be particularly applied for epidemiological studies of C. pseudotuberculosis isolates. We found that ADSRRS-fingerprinting is a rapid method offering good discrimination power, excellent reproducibility and may be applied for epidemiological studies of intraspecific genetic relatedness of C. pseudotuberculosis strains.
ON DESIGN OF UNCONVENTIONAL HIGH ASPECT RATIO "JOINED-WING" TYPE AIRCRAFT (2002)

Unmanned Sensor Craft air vehicles have been proposed as the air-breathing component of a future intelligence, surveillance, and reconnaissance (ISR) infrastructure to provide revolutionary capabilities. Such craft must take advantage of high aspect ratio (AR) wings for aerodynamic efficiency, and may also be required to enclose an antenna in a diamond aircraft planform. A large proportion of fuel must be carried, and loiter is at high altitudes for a few days in each flight. This implies that a wide CL–altitude capability is required. This paper is concerned with aspects of configuration and design studies of high AR Sensor Craft. Implications of typical flight envelope on wing design aspects have been mentioned. Using Panel and Euler codes, results are presented for configurations with uncambered wing sections and then for configurations with designed camber and twist (trimmed for neutral stability). The designed case displays considerable reduction in LE suction, yet maintaining the lift, drag and near-elliptic wing loading characteristics. Results of an inverse design application are shown here, and further work is proposed in several areas.
Genome‐wide profiling of bone reveals differentially methylated regions in osteoporosis and osteoarthritis (2012)

Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.
A stack decoder approach to approximate string matching (2010)

We present a new efficient algorithm for top-N match retrieval of sequential patterns. Our approach is based on an incremental approximation of the string edit distance using index information and a stack based search. Our approach produces hypotheses with average edit error of about 0.29 edits from the optimal SED result while using only about 5% of the CPU computation.
Using a Mobile, Agent-based Environment to support Cooperative Software Processes (2001)

Cooperative Software Engineering (CSE) means that large-scale, software development and maintenance can be conducted in a distributed organisation or across organisations. CSE can be characterised by distributed process fragments, partly shared workspaces, cooperation planning, and frequent interactions in intra/inter-workspaces. To support CSE processes, we must deal with dynamic, unpredictable processes as well as stable, repeatable processes with totally different characteristics. Traditional workflow and process systems offer good support for stable, pre-planned processes, providing user agendas, invocation of tools, presentation of process state etc. Multi-agent systems are well suited to model and support users involved in cooperative processes. By combining these two technologies, processes with characteristics similar to cooperative software engineering processes can be modelled and supported more completely.\n\nThe thesis presents a framework called CAGIS Process Centred Environment (PCE), for combining a workflow system with a multi-agent system. These are the main parts of the thesis:\n\n- A multi-agent architecture to support cooperative processes. This architecture is particularly useful in modelling and providing support for cooperative activities where software agents act on behalf of the user. The design and implementation of this architecture is described.\n\n-A workflow system to support distributed mobile processes. This workflow system allows processes to be fragmented into smaller sub-processes that can be distributed over several workspaces and moved between these workspaces.\n\n-A gluing framework to specify the interaction between the workflow system and the multi-agent architecture. The gluemodel defines the relationships between software agents and process fragments (sub-processes), and a GlueServer is used as a middleware between a workflow tool and a multi-agent system. Results from applying the GlueModel framework on a cooperative software engineering (CSE) process is also described.\n\n- A Evaluation of the framework by modelling three practical cases:\n\n- A conference organising process is modelled in three different process environments (including our own), and evaluated according to modelling completeness and adaptability to process changes.\n\n- A CSE scenario describing a software and maintenance process in a Norwegian software company is modelled to show usefulness of the gluing framework.\n\n- A project organisation scenario used to demonstrate how software agents can be used in CAGIS Process Centred Environment to deal with evolution of distributed, fragmented workflow models.
Neuroprotection against Traumatic Brain Injury by a Peptide Derived from the Collapsin Response Mediator Protein 2 (CRMP2) (2011)

Neurological disabilities following traumatic brain injury (TBI) may be due to excitotoxic neuronal loss. The excitotoxic loss of neurons following TBI occurs largely due to hyperactivation of N-methyl-d-aspartate receptors (NMDARs), leading to toxic levels of intracellular Ca(2+). The axon guidance and outgrowth protein collapsin response mediator protein 2 (CRMP2) has been linked to NMDAR trafficking and may be involved in neuronal survival following excitotoxicity. Lentivirus-mediated CRMP2 knockdown or treatment with a CRMP2 peptide fused to HIV TAT protein (TAT-CBD3) blocked neuronal death following glutamate exposure probably via blunting toxicity from delayed calcium deregulation. Application of TAT-CBD3 attenuated postsynaptic NMDAR-mediated currents in cortical slices. In exploring modulation of NMDARs by TAT-CBD3, we found that TAT-CBD3 induced NR2B internalization in dendritic spines without altering somal NR2B surface expression. Furthermore, TAT-CBD3 reduced NMDA-mediated Ca(2+) influx and currents in cultured neurons. Systemic administration of TAT-CBD3 following a controlled cortical impact model of TBI decreased hippocampal neuronal death. These findings support TAT-CBD3 as a novel neuroprotective agent that may increase neuronal survival following injury by reducing surface expression of dendritic NR2B receptors.
Evaluation of the Genetic Toxicity of Synthetic Chemicals (XI) - a Synthetic Sulfonylurea Herbicide, Pyrazosulfuron-ethyl - (2004)

To validate and to estimate the chemical hazard playa very important role to environment and human health. The detection of many synthetic chemicals including agrochemicals that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. Pyrazosulfuron-ethyl [Ethyl-5-(4,6-dimethoxypyrimidin-2-ylcarbamoylsulfamoyl)-1-methylpyrazole-4-carboxylate, C_(14)H_(18)N_6O_7S, M, W.=414,39, CAS No. 93697-74-6], is one of well known rice herbicide belong in the sulfonyl urea group. To clarify the genotoxicity of this agrochemical, Ames bacterial reversion assay, in vitro chromosomal aberration assay with Chinese hamster lung (CHL) fibroblast and bone marrow micronucleus assay in mice were subjected. In Ames assay, although pyrazosulfuron-ethyl revealed cytotoxic at 5,000-140 ㎍/plate in Salmonella typhimurium TA100, no dose-dependent mutagenic potential in 4.4~70 ㎍/plate of S. typhimurium TA 98, TA 100, TA1535 and TA 1537 both in thc absence and presence of S-9 metabolic activation system was observed. Using CHL fibroblasts, the 50% cell growth inhibition concentration (IC_(50)) of pyrazosulfuron-ethyl was determined as 1,243 ㎍/mL, and no chromosomal aberration was observed both in the absence and presence of S-9 mixture in the concentration range of 311-1,243 ㎍/mL. And also, in vivo micronucleus assay using mouse bone marrow, pyrazosulfuron-ethyl revealed no remarkable induction of MNPCE (micronucleated polychromatic erythrocytes/l000 polychromatic erythrocytes) in the dose range of 625-2,500 mg/kg body weight when administered orally. Consequently, Ames bacterial gene mutation with Salmonella typhimurium, in vitro chromosome aberration with mammalian cells and in vivo bone marrow micronucleus assay revealed no clastogenic potential of pyrazosulfuron-ethyl in this study.
A Note on the Interrelationship Between Wetting and Nonwetting Phase Relative Permeability (1951)

In a recent publication wetting phase relative permeability was expressedas: (Equation 1) and it was stated that a similar expression applied, mutatis mutandis, tonon-wetting phase relative permeability; i.e., (Equation 2) In Equations (1) and (2), Sw and So are respectively the wetting andnon-wetting phase saturations as a fraction of the pore volume; Pc is thecapillary pressure; I, the wetting phase electrical resistivity index; IN, theanalogous non-wetting phase electrical resistivity index and Krw and Krnw, thewetting and non-wetting phase relative permeabilities. Equation (3) is interesting because it expresses the nonwetting phaserelative permeability of a porous medium at any saturation as a function of thewetting phase relative permeability at that saturation, the saturation itselfand parameters which bear directly on the distribution within the pores of thenon-wetting and wetting phase fluid networks. It is thus inherentlyplausible. Equation (3) is not readily checked against experimental data since fewreliable relative permeability figures have appeared in the literature; also nopublished information exists on the probable relationship between IN and So.However, if the Krw and Krnw figures of Leverett for unconsolidated sands areused in conjunction with the relationship I = Sw-2 for sands of this type, itis possible for Equation (3) to compute IN as a function of So. The results areshown in the accompanying figure and it will be seen that IN = So-1.72. Asynthetic sandstone for which Muskat quotes relative permeability data, alsogives a straight line plot between IN and So if I = Sw-1.8 is assumed. (Aresistivity index exponent of 1.8 appears to be the best average forconsolidated porous media.) T.N. 93
Fast decoding of tagged message formats (2002)

Many important protocols, such as Q.2931 or any protocol based on the ASN.1 basic encoding rules, are transmitted using tagged message formats, in which a message can be considered as a sequence of interleaved tag and data fields, where tag fields define the meaning of subsequent fields. These messages are computationally expensive to decode, partly because decoding each data field requires resting one or more tag fields. Evidence suggests that in some applications, although the potential space of message encodings may be very large, only a small number of message layouts are seen frequently, and thus some of the work required in decoding can be amortized over many messages. This paper analyzes the use of run-time code generation to generate optimized decoding instruction sequences for received messages matching previously observed layouts, and describes a prototype system that applies the techniques to decoding the Q.2931 and ASN.1 BER protocols. In the average case, substantial performance gains are seen.
Infrared spectroscopy as a tool for discrimination between sensitive and multiresistant K562 cells (2002)

Fourier transform infrared spectroscopy was performed on human leukemic daunorubicin-sensitive K562 cells and their multiresistant counterpart derived by selection. Statistical analysis, including variable reduction and linear discriminant analysis was performed on sensitive and multiresistant cells spectra in order to establish a diagnostic tool for multiresistant pattern. For each of the two methods of data reduction tested [genetic algorithm or principal component analysis (PCA)] discrimination between the two cell lines was found to be possible. The best results, obtained with PCA-reduction, showed an accuracy of 93% on a distinct test set of spectra. These results demonstrate the efficiency of Fourier transform infrared spectroscopy for classification. Further analysis of the spectral differences indicated that discrimination between resistant and sensitive cells was based on variations in all cellular contents. Lipid and nucleic acid decreased, relatively, while the protein content increased.
Optical devices based on tunable scattering material in air-silica microstructured fiber (2002)

Summary form only given. We present a new class of tunable optical devices based on the incorporation of scattering material into air-holes of an air-silica microstructured fiber. Previous examples of tunable guiding properties in optical fibers have relied on achieving bulk changes in the refractive index of infused material, such as polymer. In contrast, our devices rely on the use of a material whose refractive index varies spatially on a scale comparable to the light wavelength, thus giving rise to scattering. Our ability to adjust the magnitude of the scattering cross section offers a novel mechanism for manipulating light propagation in these fibers. We use polymer-dispersed liquid-crystal (PDLC) as the tunable scattering agent.