gebhart/patrepeval huggingface dataset:
pH sensing by FAK-His58 regulates focal adhesion remodeling (2013)

Intracellular pH (pHi) dynamics regulates diverse cellular processes, including remodeling of focal adhesions. We now report that focal adhesion kinase (FAK), a key regulator of focal adhesion remodeling, is a pH sensor responding to physiological changes in pH. The initial step in FAK activation is autophosphorylation of Tyr397, which increased with higher pHi. We used a genetically encoded biosensor to show increased pH at focal adhesions as they mature during cell spreading. We also show that cells with reduced pHi had attenuated FAK-pY397 as well as defective cell spreading and focal adhesions. Mutagenesis studies indicated FAK-His58 is critical for pH sensing and molecular dynamics simulations suggested a model in which His58 deprotonation drives conformational changes that may modulate accessibility of Tyr397 for autophosphorylation. Expression of FAK-H58A in fibroblasts was sufficient to restore defective autophosphorylation and cell spreading at low pHi. These data are relevant to understanding cancer metastasis, which is dependent on increased pHi and FAK activity.
Whole-body optical imaging of green fluorescent protein-expressing tumors and metastases (2000)

We have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. We have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-microm diameter tumor was detectable at a depth of 0.5 mm whereas a 1, 800-microm tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.
Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy (2012)

AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade.
Incidence, outcomes, and cost of foot ulcers in patients with diabetes. (1999)

The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.
Cross-linked block copolymer micelles: functional nanostructures of great potential and versatility (2006)

Supramolecular self assembly techniques have provided a versatile means by which to selectively assemble polymer molecules into well-defined three dimensional core-shell nanostructures. The covalent stabilisation and tailoring of these dynamic nanostructures can be achieved using a range of chemistries within the assembly to afford robust functional nanoparticles. Many examples of the stabilisation, functionalisation and decoration of these nanoparticles have been reported in the literature and this tutorial review will focus on these recent developments and highlight their potential applications.
Skeeter Buster: A Stochastic, Spatially Explicit Modeling Tool for Studying Aedes aegypti Population Replacement and Population Suppression Strategies (2009)

We demonstrate that the incorporated stochasticity and level of spatial detail have major impacts on the simulated population dynamics, which could potentially impact predictions in terms of control measures. The capacity to describe population genetics confers the ability to model the outcome of genetic control methods. Skeeter Buster is therefore an important tool to model Ae. aegypti populations and the outcome of vector control measures.
STUDIES ON TOMAYMYCIN, A NEW ANTIBIOTIC. I ISOLATION AND PROPERTIES OF TOMAYMYIN (1972)

Tomaymycin, a new antiphage antibiotic is produced by cultivation of Streptomyces achromogenes var. tomaymyceticus in a lactose-bouillon medium enriched with yeast extract and phosphate salts. The active substance can be extracted from the culture filtrate by carbon adsorption and further purified by silica column chromatography. Tomaymycin is obtained in crystalline form as a molecular complex with methanol. The complex occurs as colorless platelets, m.p. 145-146°C, [α]20D + 423° (c 0.5, pyridine), λmax 224, 237, 260, 320 mμ (in methanol). The molecular formula is C16H20O4N2. The antiphag°e activity is strong against Escherichia coli T1, T3 phages and Bacillus subtilis M-2, SP-10 phages. Tomaymycin has also antimicrobial activity against Grampositive bacteria. The LD50 (i.p.) of tomaymycin for mice is estimated at 3.0 mg/kg.
Cholesterol crystal embolization in rat brain: a model for atheroembolic cerebral infarction. (1980)

Acute and delayed effects of embolizing cerebral surface vessels with cholesterol crystals were studied by direct observation in anesthetized rats and rabbits, using an open-skull technique, and by histological examination of brains at intervals of one day and one week following embolization. The number and size spectrum of crystals, which were infused into the ipsilateral internal carotid artery, were believed to approximate those released by a rupturing large atheromatous plaque in man, but the other lipid materials contained in such plaques were intentionally excluded. It was found that cholesterol crystals had only limited ability to impede blood flow in the 20--80 mu diameter arteries in view. They were also inert within the lumen, causing no vessel wall reaction even after a week; nor was any evidence seen of a thrombogenic effect. Local caliber changes in the containing artery were reproducibly seen, with dilatation of the arterial segment proximal to the embolus and narrowing of the segment in fro...
당뇨쥐에서 Protein Tyrosine Kinase Pathway 의 활성화 (1998)

당뇨망막병증에서 혈관장애가 오는 기전은 아직 확실하지 않으나, 망막모세혈관폐쇄에 의해 망막허혈이 생기고, 신생혈관 등 여러 임상증상이 나타난다. 저자는 microvascular retinopathy 가 있는 Zucker diabetic fatty rat를 이용하여, 세포증식에 중요한 것으로 알려진 protein tyrosine kinase (PTK) pathway가 활성화되는지를 알아보고자 하였다. 12마리의 Zucker diabetic fatty rat와 대조군으로 12마리의 lean Zucker rat를 이용하였다. Western blot을 이용하여 망막조직내의 혈관증식인자, phosphotyrosine, PTK pathway intermediates 등을 검사하였다. 당뇨쥐망막에서 대조군에 비해 VEGF, PDGF, phosphotyrosine, PCNA, MAPK, PI3-K 등의 level이 증가하였다. 이상의 결과로, 이 당뇨모델에서 생기는 microvascular retinopathy의 발생기전에 VEGF, PDGF의 증가로 인한 MAPK, PI3-K 등의 PTK pathway의 활성화가 관련됨을 알 수 있었다(한안지 39:939-948, 1998).
Cancer immunotherapy: the beginning of the end of cancer? (2016)

These are exciting times for cancer immunotherapy. After many years of disappointing results, the tide has finally changed and immunotherapy has become a clinically validated treatment for many cancers. Immunotherapeutic strategies include cancer vaccines, oncolytic viruses, adoptive transfer of ex vivo activated T and natural killer cells, and administration of antibodies or recombinant proteins that either costimulate cells or block the so-called immune checkpoint pathways. The recent success of several immunotherapeutic regimes, such as monoclonal antibody blocking of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD1), has boosted the development of this treatment modality, with the consequence that new therapeutic targets and schemes which combine various immunological agents are now being described at a breathtaking pace. In this review, we outline some of the main strategies in cancer immunotherapy (cancer vaccines, adoptive cellular immunotherapy, immune checkpoint blockade, and oncolytic viruses) and discuss the progress in the synergistic design of immune-targeting combination therapies.
Integrated-Optics Multimode-Interference Wavelength Division Multiplexer for Optical Communication (1999)

Abstract An integrated-optics multimode-interference 1.3 1.55-mum wavelength division mul tiplexer demultiplexer for optical communication is reported. We have found that the device length can be reduced by adopting a restricted-resonance multimode-interference scheme and a lower beat length ratio. The former allows the device length to be 3 times shorter, and the latter has been found to be able to avoid the wavelength insensitivity of the multimode-interference effects. Modal propagation analysis was used to investigate transmission characteristics of the device. Simulation results show that a demultiplexer with contrasts of 40 dB at 1.3-mum wavelength and 34.5 dB at 1.55 mum can be achieved at an optimum coupler length of 435.5 mum. We have also discussed the fabrication and operation tolerances of the wavelength multiplexer and the effect of the wavelength-dependent refractive index.
Three‐dimensional reconstruction of the temporal bone (1990)

Study of the complex anatomy and pathology of the temporal bone has traditionally used microscopy which permits analysis in only two dimensions. Recent advances in bioimaging technology have permitted visualization and reconstruction of computed tomography images in three dimensions. We have developed a technique that applies this technology in the imaging and reconstruction of human temporal bones. Data taken from serial histologic sections of the temporal bone are entered into a computer. The sections are edited and, through the use of specially developed software, a realistic three-dimensional reconstruction is produced. The reconstructed image can be rotated along any of three axes, and structures within the temporal bone can be isolated for more detailed analysis. Applications for the study of pathologic conditions of the temporal bone will be discussed.
Construction of a mammalian transducing vector from the genome of Moloney murine leukemia virus (1982)

A 0.9-kilobase DNA fragment from the genome of Moloney murine leukemia virus, including the viral long terminal repeat, was covalently linked to the herpes simplex virus I thymidine kinase (tk) gene whose promoter was previously removed. The hybrid DNA structure was introduced into the chromosome of tk- mouse cells at single copy numbers, via transfection procedures. Cells expressing the newly introduced tk gene were identified by the HAT selection procedure and analyzed for tk- and moloney murine leukemia virus-specific DNA and RNA sequences by blot hybridization procedures. Expression of the tk gene is dependent on function(s) provided in cis by the viral DNA fragment. Vectors derived from this region are termed rGag (rG) vectors.
Cooperative binding of distamycin-A to DNA in the 2:1 mode (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCooperative binding of distamycin-A to DNA in the 2:1 modePatricia Fagan and David E. WemmerCite this: J. Am. Chem. Soc. 1992, 114, 3, 1080–1081Publication Date (Print):January 1, 1992Publication History Published online1 May 2002Published inissue 1 January 1992https://doi.org/10.1021/ja00029a042RIGHTS & PERMISSIONSArticle Views135Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (299 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Biosynthesis of Natural Rubber and Other Natural Polyisoprenoids (2004)

Abstract Introduction Occurrence of Polyisoprene Chemical Properties of Rubber The Latex Vessel System Composition of Latex Molecular Weight of Rubber Historical Outline Rubber Precursors Rubber Formation on Rubber Particles Stereochemistry of Rubber Biosynthesis Initiator of Rubber Synthesis Biosynthesis Pathway in Hevea brasiliensis Formation of IPP Initiation of Rubber Molecules Chain‐Elongation of Rubber 13 C‐NMR Study of Rubber Molecules Enzymes in Hevea brasiliensis Enzymes for the Formation of Mevalonic Acid Enzymes for the Formation of IPP Rubber Transferase Genetic Basis Rubber Biosynthesis‐Related Proteins Defense‐Related Proteins Latex Allergens Other Enzymes in Hevea Rubber Biosynthesis Pathways and Genes in Guayule and other Organisms Guayule Rubber Biosynthesis Rubber Synthesis in Indian Rubber Tree Rubber Synthesis in Fungi Production in Transgenic Plants and Recombinant Microorganisms Outlook and Perspectives Relevant Patents Stimulation of Rubber Yield and Rubber‐Producing Plants Rubber Biosynthetic Genes and their Transformation Synthetic Use of Enzymes from H. brasiliensis Enzymes from Hevea and their DNA Sequences Acknowledgements
The Physiological Principle of Minimum Work (1926)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Likelihood ratio gradient estimation for stochastic systems (1990)

Consider a computer system having a CPU that feeds jobs to two input/output (I/O) devices having different speeds. Let θ be the fraction of jobs routed to the first I/O device, so that 1 - θ is the fraction routed to the second. Suppose that α = α(θ) is the steady-sate amount of time that a job spends in the system. Given that θ is a decision variable, a designer might wish to minimize α(θ) over θ. Since α(·) is typically difficult to evaluate analytically, Monte Carlo optimization is an attractive methodology. By analogy with deterministic mathematical programming, efficient Monte Carlo gradient estimation is an important ingredient of simulation-based optimization algorithms. As a consequence, gradient estimation has recently attracted considerable attention in the simulation community. It is our goal, in this article, to describe one efficient method for estimating gradients in the Monte Carlo setting, namely the likelihood ratio method (also known as the efficient score method). This technique has been previously described (in less general settings than those developed in this article) in [6, 16, 18, 21]. An alternative gradient estimation procedure is infinitesimal perturbation analysis; see [11, 12] for an introduction. While it is typically more difficult to apply to a given application than the likelihood ratio technique of interest here, it often turns out to be statistically more accurate. In this article, we first describe two important problems which motivate our study of efficient gradient estimation algorithms. Next, we will present the likelihood ratio gradient estimator in a general setting in which the essential idea is most transparent. The section that follows then specializes the estimator to discrete-time stochastic processes. We derive likelihood-ratio-gradient estimators for both time-homogeneous and non-time homogeneous discrete-time Markov chains. Later, we discuss likelihood ratio gradient estimation in continuous time. As examples of our analysis, we present the gradient estimators for time-homogeneous continuous-time Markov chains; non-time homogeneous continuous-time Markov chains; semi-Markov processes; and generalized semi-Markov processes. (The analysis throughout these sections assumes the performance measure that defines α(θ) corresponds to a terminating simulation.) Finally, we conclude the article with a brief discussion of the basic issues that arise in extending the likelihood ratio gradient estimator to steady-state performance measures.
Automated reprojection-based pixel shader optimization (2008)

We present a framework and supporting algorithms to automate the use of temporal data reprojection as a general tool for optimizing procedural shaders. Although the general strategy of caching and reusing expensive intermediate shading calculations across consecutive frames has previously been shown to provide an effective trade-off between speed and accuracy, the critical choices of what to reuse and at what rate to refresh cached entries have been left to a designer. The fact that these decisions require a deep understanding of a procedure's semantic structure makes it challenging to select optimal candidates among possibly hundreds of alternatives. Our automated approach relies on parametric models of the way possible caching decisions affect the shader's performance and visual fidelity. These models are trained using a sample rendering session and drive an interactive profiler in which the user can explore the error/performance trade-offs associated with incorporating temporal reprojection. We evaluate the proposed models and selection algorithm with a prototype system used to optimize several complex shaders and compare our approach to current alternatives.
Laser emission and photodetection in an InP/InGaAsP layer integrated on and coupled to a Silicon-on-Insulator waveguide circuit (2006)

Laser emission from an InP/InGaAsP thin film epitaxial layer bonded to a Silicon-on-Insulator waveguide circuit was observed. Adhesive bonding using divinyl-tetramethyldisiloxane-benzocyclobutene (DVS-BCB) was used to integrate the InP/InGaAsP epitaxial layers onto the waveguide circuit. Light is coupled from the laser diode into an underlying waveguide using an adiabatic inverted taper approach. 0.9mW optical power was coupled into the SOI waveguide using a 500mum long laser. Besides for use as a laser diode, the same type of devices can be used as a photodetector. 50mum long devices obtained a responsivity of 0.23A/W.
Control: the social boundaries of age (2012)

The variety in the status of the aged in different societies is enormous. Comparative anthropological research on the aged in various cultural milieux has revealed relatively few common denominators (see, e.g., Simmons 1945; Cowgill and Holmes 1971; Myerhoff and Simic 1978; Amoss and Harell 1981a: Fry 1980; Sokolovsky 1983). Before discussing the sources of such differences, it may be useful to illustrate their range.
Measuring Receptor-Mediated Cell Adhesion Under Flow: Cell-Free Systems (2003)

Leukocytes must bind to vascular endothelium under conditions of flow to perform their appropriate physiological functions, which require trafficking into and out of the tissue space surrounding blood vessels. Trafficking into tissues is required of neutrophils during the acute inflammatory response, and during trafficking of lymphocytes into lymphoid tissue. Egress from blood lumen to tissue involves a series of adhesion-dependent steps, each of which involve different leukocyte adhesion receptors and counterreceptors on the endothelium. Transient adhesion, or rolling, of leukocytes over endothelial cells is a prerequisite to firm attachment and transendothelial migration (1,2).
Effects of Preanalytical Factors on the Molecular Size of Cell-Free DNA in Blood (2005)

Recently, plasma DNA analysis has been increasingly explored for different clinical diagnostic purposes. Previous studies have shown that the concentration of plasma DNA is increased in patients with neoplastic diseases (1), pregnancy-related complications (2)(3), trauma(4), and certain autoimmune diseases (5). In addition to quantitative analysis, qualitative changes in plasma DNA have also been investigated in different physiologic and pathologic conditions. In this regard, our group has shown that fetal DNA is shorter than the maternal counterpart in the plasma of pregnant women (6), and this has allowed the enrichment of fetal DNA from maternal plasma by size fractionation (7). It has also been shown that plasma DNA fragments are longer in patients suffering from a variety of neoplastic diseases (8). In addition, circulating Epstein–Barr virus DNA molecules in patients with nasopharyngeal carcinoma have been found to consist mainly of short DNA fragments <180 bp in size (9). Because the samples collected from patients and healthy controls in these studies were usually collected at different time points and under different conditions, it is important to ensure that the observed variations in the sizes of plasma DNA are the result of biological changes rather than artifacts attributable to differences in sample handling. Therefore, in this study, we investigated the effects of several preanalytical factors, including clotting, delayed separation of blood cells from plasma, freezing–thawing, and storage, on the integrity of circulating cell-free DNA.

We recruited 27 healthy volunteers for modules 1 to 4 of the study. Venous blood (30 mL) was collected from each volunteer into eight tubes containing EDTA and one plain tube. The samples serving as references were processed immediately after collection. Plasma was separated from the blood cells by centrifugation at 1600 g for 10 min, and the plasma was then microcentrifuged at 16 000 g …
Construcción de conocimiento profesional acerca de la intervención curricular en el aprendizaje de las matemáticas en un entorno virtual (2011)

La investigacion tiene como objetivo identificar caracteristicas del proceso de instrumentalizacion del conocimiento de didactica de la matematica de estudiantes para asesores curriculares cuando diagnostican dificultades de aprendizaje de las matematicas en estudiantes de educacion primaria en un entorno de aprendizaje b-learning construido alrededor del analisis de casos sobre la ensenanza de las matematicas. El analisis ha permitido caracterizar el aprendizaje de los asesores en formacion como un cambio en el discurso realizado mediante la integracion paulatina y uso de manera pertinente de las ideas teoricas procedentes de la didactica de la matematica en la resolucion de tareas de diagnosticar y planificar una nueva intervencion didactica. Ademas, los resultados nos han permitido identificar las aportaciones a los debates en-linea en forma de refutaciones como un mecanismo que ha favorecido la instrumentalizacion de las ideas teoricas puesta de manifiesto en el cambio de discurso generado. Los resultados indican que los procesos de interaccion en los debates en-linea utilizando el lenguaje escrito ayudaron a instrumentalizar la informacion teorica durante la resolucion de problemas profesionales, y por tanto el aprendizaje generado en estos entornos. Las formas de participacion en los debates pueden ser explicadas por la existencia de dos identidades distintas entre los estudiantes de psicopedagogia con y sin experiencia docente lo que condiciono los procesos interactivos y el aprendizaje.