gebhart/patrepeval huggingface dataset:
Preclinical models for pediatric solid tumor drug discovery: current trends, challenges and the scopes for improvement (2012)

In many solid tumors, common differences between pediatric and adult cancers have been observed, and therefore, clinical trials for pediatric solid tumors must be conducted on the basis of preclinical observations in pediatric solid tumor models. There is a need to invest in extensive preclinical testing on pediatric solid tumor models. None of the preclinical models can fully recapitulate the human cancers. Therefore, these limitations must be considered while conducting a preclinical trial. The dose and schedule of drugs used for preclinical testing must be clinically relevant. While testing the efficacy of drugs, the markers of apoptosis, drug resistance, hypoxia and tumor-initiating cells can inform us about the long-term therapeutic response of a cancer.
A Multiprocessor Architecture for the (M, L)-Algorithm Suitable for VLSI Implementation (1986)

The <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(M, L)</tex> -algorithm has been widely used in speech and image encoding. Recently, use of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(M, L)</tex> -Iike algorithms has been suggested for decoding phase codes. With its ever-increasing use, there arises a need to explore architectures suitable for real-time applications. Toward this end, we present a multiprocessor architecture for the <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(M, L)</tex> algorithm that employs an SIMD (single instruction-multiple data) machine structure. The considerations involved in interconnection network design are discussed. The main functions of the network controller are switch state selection and synchronization. The number of switching elements required is significantly less than the elements required in the universal permutation network. These features make this architecture suitable for VLSI implementation. The tradeoff between number of processors and encoding time is also discussed.
Optimal estimation of vanishing points in a Manhattan world (2011)

In this paper, we present an analytical method for computing the globally optimal estimates of orthogonal vanishing points in a “Manhattan world” with a calibrated camera. We formulate this as constrained least-squares problem whose optimality conditions form a multivariate polynomial system. We solve this system analytically to compute all the critical points of the least-squares cost function, and hence the global minimum, i.e., the globally optimal estimate for the orthogonal vanishing points. The same optimal estimator is used in conjunction with RANSAC to generate orthogonal-vanishing-point hypotheses (from triplets of lines) and thus classify lines into parallel and mutually orthogonal groups. The proposed method is validated experimentally on the York Urban Database.
Patterned Single-Wall Carbon Nanotube Transparent Conducting Films for Liquid Crystal Switching Electrodes (2011)

We have fabricated transparent and electrically conductive single-wall carbon nanotube (SWCNT) thin films for liquid crystal switching electrodes. The SWCNT film had a sheet resistance of 91.02 Ω/□ and a transmittance of 92.33% at 550 nm. Our CNT-based transparent conducting film (TCF) patterning technique is a combination of photolithography and O 2 plasma etching. We were able to pattern CNT-TCFs with a high resolution, and as small as 4 µm, and to fabricate them with various shapes and patterns. Our CNT-TCFs were used to successfully switch liquid crystal cells with 100 µm and 15 mm line widths.
INVESTIGATION OF ELECTROWETTING-BASED MICROFLUIDICS FOR REAL-TIME PCR API’LICATIONS (2003)

An investigation was conducted to determine the suitability of electrowetting-based droplet actuation for microfluidic PCR applications. We experimentally verified that droplets containing standard PCR reagents could be microactuated with the same facility previously demonstrated for droplets of deionized water or salt solution. We further verified that the manipulations and the environment inside the electrowetting chip did not inhibit PCR and we were able to successfully perform real-time PCR assays in 300 nL droplets within the electrowetting chip.
Dedifferentiation of Adult Human Myoblasts Induced by Ciliary Neurotrophic Factor In Vitro (2005)

Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular effects within the nervous system. However, recent studies indicate that its receptor can be highly expressed in denervated skeletal muscle. Here, we investigated the direct effect of CNTF on skeletal myoblasts of adult human. Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts at a clonal level to dedifferentiate into multipotent progenitor cells--they not only could proliferate for over 20 passages with the expression absence of myogenic specific factors Myf5 and MyoD, but they were also capable of differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle cells, and adipocytes. These "progenitor cells" retained their myogenic memory and were capable of redifferentiating into myotubes. Furthermore, CNTF could activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway, was able to abolish the effects of CNTF on both myoblast fate and MRF expression. Our results demonstrate the myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway.
Targeting adenosine for cancer immunotherapy (2018)

Immune checkpoint antagonists (CTLA-4 and PD-1/PD-L1) and CAR T-cell therapies generate unparalleled durable responses in several cancers and have firmly established immunotherapy as a new pillar of cancer therapy. To extend the impact of immunotherapy to more patients and a broader range of cancers, targeting additional mechanisms of tumor immune evasion will be critical. Adenosine signaling has emerged as a key metabolic pathway that regulates tumor immunity. Adenosine is an immunosuppressive metabolite produced at high levels within the tumor microenvironment. Hypoxia, high cell turnover, and expression of CD39 and CD73 are important factors in adenosine production. Adenosine signaling through the A2a receptor expressed on immune cells potently dampens immune responses in inflamed tissues. In this article, we will describe the role of adenosine signaling in regulating tumor immunity, highlighting potential therapeutic targets in the pathway. We will also review preclinical data for each target and provide an update of current clinical activity within the field. Together, current data suggest that rational combination immunotherapy strategies that incorporate inhibitors of the hypoxia-CD39-CD73-A2aR pathway have great promise for further improving clinical outcomes in cancer patients.
Experimental Bacterial Endocarditis After Dental Extractions in Rats with Periodontitis (1987)

The development of bacterial endocarditis was analyzed after dental extractions in rats with or without periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars and placing the animals on a high sucrose diet for 14 weeks. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hr later the maxillary first molars were extracted. The animals were killed 72 hr after the extractions. In rats with periodontal disease, extractions resulted in a 48% (14 of 29) incidence of bacterial endocarditis, most cases of which were due to Streptococcus spp. (one was caused by Staphylococcus aureus). In contrast, when the teeth with a healthy periodontium were extracted, only 6% (one of 15) of the rats developed endocarditis. When catheters were placed in animals with periodontal disease but no extractions were performed, no endocarditis occurred.
A cellular protein that binds to the 5'-noncoding region of poliovirus RNA: implications for internal translation initiation. (1989)

Initiation of translation on poliovirus mRNA occurs by internal binding of ribosomes to a region within the 5'-noncoding portion of the mRNA. The mechanistic details and trans-acting factors involved in this event are not understood fully. We used a mobility-shift electrophoresis assay to identify a specific RNA-protein complex, which can form between an RNA fragment that contains nucleotides 559-624 of the poliovirus 5' UTR (untranslated region) and a component or components of a HeLa cell extract. Complex formation was reduced greatly in a reticulocyte lysate or a wheat-germ extract. A 52-kD polypeptide (p52) has been identified as part of the protein-RNA complex by use of an UV cross-linking assay. This polypeptide apparently is not a known translation initiation or elongation factor. The possible involvement of p52 in translation initiation of poliovirus protein synthesis is discussed.
Mechanophotopatterning on a Photoresponsive Elastomer (2011)

Photopatterning of a photoreversible cova­lent elastomeric network under mechanical strain, or mechanophotopatterning, provides a facile approach to fabricate complex topographical features using elementary irradiation schemes. A photoresponsive material is deformed in two dimensions and irradiated through a mask, resulting in a transparent material with topography that reflects the concentric rings of the mask. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Analysis of Repeated Measurements of Animals (1971)

An example of non-random repeated information of lactating rats is analyzed to clarify statistical procedures that avoid misleading inferences from such data. Recognition of split-plot structure and examination of heterogeneous correlation of data are emphasized. Methods are outlined for testing the variance-covariance structure, and multivariate procedures are discussed for testing hypotheses about effects of repeated factors (e.g., time) and for comparing profiles of responses (over time) for two treatment groups.
Fate of Methyl Bromide in Fumigated Soils (1996)

Recent controversy over the potential role of methyl bromide (MeBr) in damaging the ozone layer has spurred interest in increasing our understanding of the transformation and movement of this fumigant after it is applied to soil. Our research indicates MeBr is rapidly volatilized from fumigated soil (within the first 24 hours) and volatility significantly increases with temperature (35° C > 25° C = 15° C) and moisture (0.03 bar > 0.3 bar > 1 bar > 3 bar). Degradation of MeBr, measured by production of bromide ion (Br-), was also directly related to temperature and moisture. Undisturbed soil column studies indicated that MeBr rapidly volatilized (> 50% of the MeBr flux occurred in 48 h) but did not leach into subsurface soil. Residual MeBr was degraded in the soil column, evident by the high concentrations of Br- in the leachate water. In field studies, MeBr also volatilized rapidly from soil, but a significant portion of the MeBr was degraded (30% after 2 d). These studies provide pertinent information for assessing the fate of MeBr in soil, which should lead to more informed decisions regulating its use.
Control system and dynamic model validation for a parallel hybrid electric vehicle (1999)

Contains a description of mathematical modeling, analysis, and simulation in an iterative process including development of parallel hybrid electric vehicle (PHEV) hardware, system performance measures, computer control software, and complete PHEV powertrain system synthesis. A PHEV is synthesized using a conventional spark ignited (SI) internal combustion engine (ICE) power plant-alternator combination, a dry clutch, and manual transmission/differential with an AC-induction traction motor attached after the differential. An operating strategy for this PHEV is presented. Simulations and test data are presented to demonstrate model validation.
Mutation in the ATP-binding pocket of the ABL kinase domain in an STI571-resistant BCR/ABL-positive cell line. (2002)

The major mechanism of action of STI571 is a competitive interference with the ATP-binding site of the Bcr/Abl tyrosine kinase. In the BCR/ABL-positive cell line KBM5, we studied cellular events associated with the in vitro acquisition of resistance to STI571. The emergence of the STI571-resistant phenotype was accompanied by only a marginal increase in the number of copies of the BCR/ABL gene and its level of expression. The activity of the Bcr/Abl kinase (level of autophosphorylation) in resistant cells was, however, incompletely inhibited by STI571, and the acquisition of the high degree of resistance was associated with a single-point mutation leading to a substitution of a threonine-to-isoleucine at position 315 of Abl. In the resistant KBM5-STI571(R1.0) cells, 20% of the BCR/ABL transcripts and 10% of BCR/ABL gene copies on the DNA level were mutated. The mutation was present in all 10 STI571-resistant clones derived from low density clonogenic assay, confirming its presence in all colony-forming cells but only in a fraction of the BCR/ABL gene copies in each cell. The contribution of this mutation to STI571-resistant phenotype remains unknown. Preliminary data showing partial reversibility of resistance in these cells suggest that resistance may be multifactorial. No other mutations were identified in the kinase domain of the BCR/ABL gene.
Evaluation of protocols from formal specifications: a case study with LAPD (2002)

A formal method for the specification and evaluation of protocols is presented, focusing on measures of processing requirements in a node. With this method, it is shown to be possible to define objective measures of protocol performance and to compare implementations of different protocols that provide the same service. As an example, the method is used to specify both the link access protocol on the D-channel (LAPD) and the IEEE 802.2 protocols using the augmented protocol specification language (APSL). The specification consists of a receiver and a transmitter operating concurrently at a given node and of auxiliary processes such as timers. It is also shown that APSL specifications can be used as the starting point for different development paths: automatic generation of software implementation, machine code for hardware implementations, and derivation of performance measures (average and worst-case). The use of APSL allows the use of existing PSL tools for formal verification and the generation of conformance tests. A description of APSL and an overview of LAPD are given.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ligand- and DNA-induced dissociation of RXR tetramers (1998)

Unliganded bacterially expressed RXR alpha lacking the N-terminal region AB (apo-RXR alpha delta AB) was found in solution as an apparent mixture of 165 kDa tetramers and 42 kDa monomers which could be quantitatively separated by gel filtration and non-denaturing gel electrophoresis. Under identical conditions both liganded (holo-) and apo-RAR alpha delta AB were present as single monomeric species. apo-RXR alpha delta AB tetramers, as well as dimers of the apo-RXR ligand binding domain (apo-LBD), dissociated readily into monomers when exposed to their cognate ligand 9-cis retinoic acid (9c-RA). The apo-RXR alpha delta AB tetramer bound only transiently to a cognate DR1 response element, and was converted into DR1-apo-RXR alpha delta AB homodimer complexes indistinguishable from those generated by cooperative DNA binding of apo-RXR alpha delta AB monomers. In the absence of DNA, the addition of 9c-RA greatly accelerated the formation of heterodimers with the apo-RAR alpha delta AB heterodimerization partner. No RXR alpha delta AB or RAR alpha delta AB homodimers could be observed in solution, but upon mixing of the two receptor monomers stable heterodimers could be isolated which bound to DR5 response elements in a highly cooperative manner. In these heterodimers, RXR alpha delta AB interacted with its cognate ligand as efficiently as in RXR alpha delta AB homodimers. The presence of ligand did not alter the stability of RXR alpha delta AB homodimer or RXR alpha delta AB-RAR alpha delta AB heterodimer complexes on DR1 and DR5 response elements, respectively. These in vitro data support a model in which RXR tetramers could serve as an inactive pool with the dual function of: (i) rapidly supplying large amounts of RXR heterodimerization partners upon 9c-RA generation; and (ii) allowing RXR homodimer formation on "accessible" cognate response elements in the absence of 9c-RA. These events may represent a ligand-dependent regulatory mechanism controlling the availability of the promiscuous RXR dimerization partner that is engaged in multiple nuclear receptor signalling pathways.
Targeted Therapies for Cancer 2004 (2004)

The regulatory agency approvals in the United States and Europe of imatinib mesylate (Gleevec) for patients with bcr/abl-positive chronic myelogenous leukemia, cetuximab (Erbitux) for patients with epidermal growth factor receptor overexpressing metastatic colorectal cancer, the antiangiogenesis agent bevacizumab (Avastin), and the proteasome inhibitor bortezomib (Velcade)--and the considerable public interest in new anticancer drugs that take advantage of specific genetic defects that render the malignant cells more likely to respond to specific treatment--are driving a new era of integrated diagnostics and therapeutics. The recent discovery of a drug response predicting activating mutation in the epidermal growth factor receptor gene for patients with non-small cell lung cancer treated with gefitinib (Iressa) has intensified this interest. In this review, the history of targeted anticancer therapies is highlighted, with focus on the development of molecular diagnostics for hematologic malignancies and the emergence of trastuzumab (Herceptin), an antibody-based targeted therapy for HER-2/neu overexpressing metastatic breast cancer: The potential of pharmacogenomic strategies and the use of high-density genomic microarrays to classify and select therapy for cancer are briefly considered. This review also considers the widely held view that, in the next 5 to 10 years, the clinical application of molecular diagnostics will further revolutionize the drug discovery and development process; customize the selection, dosing, route of administration of existing and new therapeutic agents; and truly personalize medical care for cancer patients.
Vascular endothelial growth factor and the regulation of angiogenesis. (2000)

The development of a vascular supply is essential not only for organ development and differentiation during embryogenesis but also for wound healing and reproductive functions in the adult Folkman, 1995). Angiogenesis is also implicated in the pathogenesis of a variety of disorders: proliferative retinopathies, age-related macular degeneration, tumors, rheumatoid arthritis, and psoriasis (Folkman, 1995; Garner, 1994). Several potential regulators of angiogenesis have been identified, including fibroblast growth factor-a (aFGF), bFGF, transforming growth factor-alpha (TGF-alpha), TGF-beta, hepatocyte growth factor/scatter factor (HGF/SF), tumor necrosis factor-alpha (TNF-alpha), angiogenin, and interleukin-8 (IL-8) (Folkman and Shing, 1992; Risau, 1997). More recently, the angiopoietins, the ligands of the Tie-2 receptor (Suri et al., 1996; Maisonpierre et al., 1997), have been identified. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific mitogen. The finding that VEGF was potent and specific for vascular endothelial cells and, unlike bFGF, freely diffusible, led to the hypothesis that this molecule plays a unique role in the regulation of physiological and pathological angiogenesis (Ferrara and Henzel, 1989: Leung et al., 1989). Over the last few years, several additional members of the VEGF gene family have been identified, including placenta growth factor (PIGF) (Maglione et al., 1991,1993), VEGF-B (Olofsson et al., 1996), VEGF-C (Joukov et al., 1996; Lee et al., 1996), and VEGF-D (Orlandini et al., 1996. Achen et al., 1998). There is compelling evidence that VEGF plays an essential role in the development and differentiation of the cardiovascular system (Ferrara and Davis-Smyth, 1997).
A quantitative account of the activation steps involved in phototransduction in amphibian photoreceptors. (1992)

1. We have undertaken a theoretical analysis of the steps contributing to the phototransduction cascade in vertebrate photoreceptors. We have explicitly considered only the activation steps, i.e. we have not dealt with the inactivation reactions. 2. From the theoretical analysis we conclude that a single photoisomerization leads to activation of the phosphodiesterase (PDE) with a time course which approximates a delayed ramp; the delay is contributed by several short first-order delay stages. 3. We derive a method for extracting the time course of PDE activation from the measured electrical response, and we apply this method to recordings of the photoresponse from salamander rods. The results confirm the prediction that the time course of PDE activation is a delayed ramp, with slope proportional to light intensity; the initial delay is about 10-20 ms. 4. We derive approximate analytical solutions for the electrical response of the photoreceptor to light, both for bright flashes (isotropic conditions) and for single photons (involving longitudinal diffusion of cyclic GMP in the outer segment). The response to a brief flash is predicted to follow a delayed Gaussian function of time, i.e. after an initial short delay the response should begin rising in proportion to t2. Further, the response-intensity relation is predicted to obey an exponential saturation. 5. These predictions are compared with experiment, and it is shown that the rising phase of the flash response is accurately described over a very wide range of intensities. We conclude that the model provides a comprehensive description of the activation steps of phototransduction at a molecular level.
Deacylation of structurally diverse lipopolysaccharides by human acyloxyacyl hydrolase. (1990)

Acyloxyacyl hydrolase, a leukocyte enzyme previously has been shown to catalyze the hydrolysis of secondary (acyloxyacyl-linked) fatty acyl chains from the nonreducing glucosamine of the lipid A region of rough Salmonella typhimurium lipopolysaccharide (LPS). We describe here the activity of this enzyme toward smooth S. typhimurium LPS and LPS from Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria meningitidis, and Neisseria gonorrhoeae. Acyloxyacyl hydrolase released the secondary acyl chains from all of these lipopolysaccharides, regardless of the location of the acyloxyacyl linkage on the diglucosamine backbone or the structure of the acyl chains. The two acyloxyacyl linkages present in each LPS molecule apparently were hydrolyzed separately, so that free fatty acids released from the different sites accumulated at different rates. The purified enzyme also removed greater than 90% of the secondary acyl chains in each LPS, indicating that the enzyme acts not only on intact LPS but also on LPS molecules that have only one secondary acyl chain. The enzyme did not release the glucosamine-linked 3-hydroxyacyl chains. The specificity and versatility of the enzyme for cleaving acyloxyacyl linkages suggest that it may be a useful reagent for studying the structure and bioactivities of lipopolysaccharides with diverse carbohydrate and lipid A structures.