gebhart/patrepeval huggingface dataset:
Generation of Complex, Static Solution Gradients in Microfluidic Channels (2006)

A microfluidic device is used to generate a complex gradient of diffusible molecules in a static solution. The gradient is precise and steady both in space and in time. This device, made from poly(dimethylsiloxane), consists of three layers. The molecules in reservoirs on the top layer diffuse through the flat middle layer of hydrogel and reach an equilibrium distribution. Microfluidic channels on the bottom layer that are in close contact with the hydrogel contain free solution that has concentration gradients based on the gradient in the gel. The gradient profile in the channel can be designed to have an arbitrary form (within the range of the existing gradient in the hydrogel) by controlling the local direction of the channel at each point.
Spatial phase separation of GaN selectively grown on a nanoscale faceted Si surface (2004)

This letter reports the growth of spatially separated hexagonal and cubic phases of GaN on a patterned Si(001) substrate by metalorganic vapor-phase epitaxy. The substrate surface was patterned with grooves having a 355 nm period. Each groove consisted of two opposed Si{111} facets that were separated by Si(001) surfaces. Epitaxial growth of GaN on this substrate began selectively on the Si{111} facets and yielded the GaN hexagonal phase. With further growth, the two hexagonal phase regions separately grown on the opposed Si{111} facets coalesced, with strongly misaligned c axes (∼110°). The GaN grown after coalescence was subsequently confirmed, by transmission electron microscopy and photoluminescence, to be of cubic phase.
STUDIES ON STREPTOCOCCUS BACTERIOPHAGE (1927)

1. The "sludge" phage obtained by Clark and Clark answers all requirements for pronouncing it identical with the classical bacteriophage. 2. The "sludge" phage failed to produce lysis in any of the 102 human pathogenic streptococci tested. 3. Numerous attempts to induce regeneration of various lytic principles by human streptococci resulted in failure. 4. It was possible, however, to "train" erysipelas streptococci to regenerate a lytic principle active against 76 per cent of strains of this group. 5. The erysipelas phage showed remarkable specificity.
The Principles of Readability. (2004)

The principles of readability are in every style manual. Readability formulas are in every word processor. What is missing is the research and theory on which they stand.
A new alternative transcript encodes a 60 kDa truncated form of integrin β3 (1994)

A cDNA for integrin beta 3 isolated from a human erythroleukaemia (HEL) cell library contained a 340 bp insert at position 1281. This mRNA, termed beta 3c, results from the use of a cryptic AG donor splice site in intron 8 of the beta 3 gene, and is different from a previously described alternative beta 3 mRNA. The predicted open reading frame of beta 3C stops at a TAG stop codon 69 bp downstream from position 1281. It starts with the signal peptide and the 404 N-terminal extracellular residues of beta 3, encompassing the ligand binding sites, followed by 23 C-terminal intron-derived residues, corresponding to a truncated form of beta 3 lacking the cysteine-rich, transmembrane and cytoplasmic domains. Expression of beta 3C mRNA was demonstrated in human platelets, megakaryocytes, endothelial cells and HEL cells by reverse transcriptase/PCR. The beta 3C transcript was also demonstrated in the mouse, suggesting its conservation through evolution. Finally, a 60 kDa polypeptide corresponding to the beta 3C alternative transcript was demonstrated in platelets by Western blotting using a polyclonal antibody raised against a synthetic peptide designed from the beta 3C intronic sequence. Taken together, these results suggest a biological role for beta 3C, the first alternative transcript showing an altered extracellular domain of a beta integrin.
Blocking of cloned and native delayed rectifier K+ channels from visceral smooth muscles by phencyclidine (2000)

We investigated the effect of phencyclidine (PCP) on three native delayed rectifier K+ currents and three channels cloned from canine and human circular colonic myocytes using voltage-clamp techniques. Native delayed rectifier K+ current in canine circular colon is composed of at least three components: (i) a rapidly activating, 4-aminopyridine-sensitive component (termed IdK(f)); (ii) a slowly activating, tetraethylammonium (TEA)-sensitive component (IdK(s)); and (iii) a rapidly activating, TEA-sensitive component, which has a steady-state inactivation curve shifted towards more negative potentials (IdK(n)). PCP blocked all three components with EC50 values of 45, 27 and 59 micromol L-1, respectively. Blocking was neither use-dependent nor voltage-dependent. Delayed rectifier K+ channels cloned from canine (Kv1.2, Kv1.5) and from human (Kv2.2) colon were expressed in Xenopus oocytes. PCP blocked all three currents with similar potency. In contrast, PCP (up to 10-4 mol L-1) did not reduce the magnitude of Ca2+-dependent outward current of large conductance Ca2+-activated K+ channels (BK channels).
Microwave performance of optically injection-locked VCSELs (2006)

The optical injection-locking technique has been demonstrated to enhance the microwave performance of fiber-optic links based on vertical-cavity surface-emitting lasers (VCSELs). We report recent advances of a comprehensive study on VCSELs under ultrahigh injection-locking conditions. The performance improvements include /spl sim/20-dB increase of both spur-free dynamic range and RF link gain, a factor of 5-10 increase in resonance frequency, as well as /spl sim/20-dB reduction in laser noise.
The cytokines IL-3 and GM-CSF regulate the transcriptional activity of retinoic acid receptors in different in vitro models of myeloid differentiation (2002)

The disruption of retinoic acid receptor (RAR) activity that characterizes human acute promyelocytic leukemia (APL) is associated with a block to granulocytic differentiation indicating that RARs are critical regulators of normal myeloid differentiation. Nevertheless, how RAR activity might be regulated in the presumably homogenous concentration of retinoids in blood and bone marrow and how these receptors might interact with specific hematopoietic cytokines to regulate normal myeloid differentiation remain unclear. Here, using several cytokine-dependent in vitro models of myeloid development, it was observed that specific hematopoietic cytokines that normally regulate myeloid lineage commitment and differentiation (interleukin-3 and granulocyte-macrophage colony-stimulating factor) trigger the enhancement of both ligand-dependent and ligand-independent transcriptional activity of both endogenous and exogenous (transiently transfected) RARs. This cytokine-mediated enhancement of RAR activity is not associated with any observed changes in expression of the RARs or their respective coactivators/corepressors. These studies define a previously unknown cytokine-RAR interaction during myelopoiesis and suggest that RAR activation might be a critical downstream event following interleukin-3 and granulocyte-macrophage colony-stimulating factor signaling during myeloid differentiation. This observation of ligand-independent activation of RARs that is mediated by certain cytokines represents a new paradigm with respect to how RAR activity might be modulated during hematopoiesis and also suggests a molecular basis for the differential sensitivity of human acute myelogenous leukemia cells to retinoids.
Characterization of Neural Responses with Stochastic Stimuli (2004)

ose response properties are not at least partially known in advance. This chapter provides an overview of some recently developed characterization methods. In general, the ingredients of the problem are: (a) the selection of a set of experimental stimuli; (b) selection of a model of response; (c) a procedure for fitting (estimation) of the model. We discuss solutions of this problem that combine stochastic stimuli with models based on an initial linear filtering stage that serves to reduce the dimensionality of the stimulus space. We begin by describing classical reverse correlation in this context, and then discuss several recent generalizations that increase the power and flexibility of this basic method. Thanks to Brian Lau, Dario Ringach, Nicole Rust, and Brian Wandell for helpful comments on the manuscript. This work was funded by the Howard Hughes Medical Institute, and the Sloan-Swartz Center for Theoretical Visual Neuroscience at New York University. 1 Reverse correlation M
Stemness-related markers in cancer (2017)

Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute towards a 'stemness' phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers and signaling pathways.
Fabrication of Microporous Thin Films from Polyelectrolyte Multilayers (2000)

A simple process has been developed to create large area, highly uniform microporous thin films. Multilayers of weak polyelectrolytes were assembled onto silicon substrates by the sequential adsorption of poly(acrylic acid) and poly(allylamine) from aqueous solution. These multilayers were then immersed briefly into acidic solution (pH ≈ 2.4) to effect a substantial and irreversible transformation of the film morphology. The resulting microporous structures are 2−3 times the thickness of the original films, possess a correspondingly reduced relative density of 1/2 to 1/3, and are stable against further rearrangement under ambient conditions. In addition, the microporous films may undergo a secondary reorganization in neutral water, leading to a morphology with more discrete throughpores. A mechanism is proposed for these transformations based on interchain ionic bond breakage and reformation in this highly protonating environment, leading to an insoluble precipitate on the substrate which undergoes spinodal decomposition with the solvent. FTIR (Fourier transform infrared spectroscopy) analysis supports the underlying chemical basis of this pH-induced phase separation, and AFM (atomic force microscopy), in situ ellipsometry, and SEM (scanning electron microscopy) have been used to monitor the morphological changes. The unique combination of properties exhibited by these microporous films makes them potential candidates for microelectronic and biomaterial applications.
Nanometer‐Scale Pores: Potential Applications for Analyte Detection and DNA Characterization (2002)

Several classes of transmembrane protein ion channels function in vivo as sensitive and selective detection elements for analytes. Recent studies on single channels reconstituted into planar lipid bilayer membranes suggest that nanometer-scale pores can be used to detect, quantitate and characterize a wide range of analytes that includes small ions and single stranded DNA. We briefly review here these studies and identify leaps in technology that, if realized, might lead to innovations for the early detection of cancer.
Complex lipid trafficking in Niemann‐Pick disease type C (2014)

Niemann-Pick disease type C (NPC) is an atypical lysosomal storage disease resulting from mutations in one of two genes, either NPC1 or NPC2. Although a neurovisceral disorder, it is above all a neurodegenerative disease in the vast majority of patients. Not an enzyme deficiency, it is currently conceived as a lipid trafficking disorder. Impaired egress of cholesterol from the late endosomal/lysosomal (LE/L) compartment is a specific and key element of the pathogenesis, but other lipids, more specially sphingolipids, are also involved, and there are indications for further abnormalities. The full function of the NPC1 and NPC2 proteins is still unclear. This review provides a reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models. It summarizes the current knowledge on the NPC1 and NPC2 proteins and their function in transport of cholesterol within the late endosomal-lysosomal compartment, with emphasis on differences between systemic organs and the brain; it also discusses regulation by membrane lipids of the NPC2-mediated cholesterol trafficking, interplay between cholesterol and sphingomyelin, the metabolic origin of glycosphingolipids stored in brain, and the putative role of free sphingoid bases in pathogenesis. Brief mention is finally made of diseases affecting other genes that were very recently shown to impact the "NPC pathway".
Quantitative determination of opioids in whole blood using fully automated dried blood spot desorption coupled to on‐line SPE‐LC‐MS/MS (2015)

Opioids are well known, widely used painkillers. Increased stability of opioids in the dried blood spot (DBS) matrix compared to blood/plasma has been described. Other benefits provided by DBS techniques include point-of-care collection, less invasive micro sampling, more economical shipment, and convenient storage. Current methodology for analysis of micro whole blood samples for opioids is limited to the classical DBS workflow, including tedious manual punching of the DBS cards followed by extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalysis. The goal of this study was to develop and validate a fully automated on-line sample preparation procedure for the analysis of DBS micro samples relevant to the detection of opioids in finger prick blood. To this end, automated flow-through elution of DBS cards was followed by on-line solid-phase extraction (SPE) and analysis by LC-MS/MS. Selective, sensitive, accurate, and reproducible quantitation of five representative opioids in human blood at sub-therapeutic, therapeutic, and toxic levels was achieved. The range of reliable response (R(2) ≥0.997) was 1 to 500 ng/mL whole blood for morphine, codeine, oxycodone, hydrocodone; and 0.1 to 50 ng/mL for fentanyl. Inter-day, intra-day, and matrix inter-lot accuracy and precision was less than 15% (even at lower limits of quantitation (LLOQ) level). The method was successfully used to measure hydrocodone and its major metabolite norhydrocodone in incurred human samples. Our data support the enormous potential of DBS sampling and automated analysis for monitoring opioids as well as other pharmaceuticals in both anti-doping and pain management regimens.
True 3-Dimensional Reconstruction of Coronary Arteries in Patients by Fusion of Angiography and IVUS (ANGUS) and Its Quantitative Validation (2000)

With ANGUS, 3D reconstructions of coronary arteries can be successfully and accurately obtained in the majority of patients.
Likelihood-enhanced fast rotation functions (2004)

Experiences with the molecular-replacement program Beast have shown that maximum-likelihood rotation targets are more sensitive to the correct orientation than traditional targets. However, this comes at a high computational cost: brute-force rotation searches can take hours or even days of computation time on current desktop computers. Series approximations to the full likelihood target have been developed that can be computed by fast Fourier transforms in minutes. These likelihood-enhanced targets are more sensitive to the correct orientation than the Crowther fast rotation function and they take advantage of information from partial solutions. The likelihood-enhanced rotation targets have been implemented in the program Phaser.
Understanding and treating triple-negative breast cancer. (2008)

Triple-negative breast cancer is a subtype of breast cancer that is clinically negative for expression of estrogen and progesterone receptors (ER/PR) and HER2 protein. It is characterized by its unique molecular profile, aggressive behavior, distinct patterns of metastasis, and lack of targeted therapies. Although not synonymous, the majority of triple-negative breast cancers carry the "basal-like" molecular profile on gene expression arrays. The majority of BRCA1-associated breast cancers are triple-negative and basal-like; the extent to which the BRCA1 pathway contributes to the behavior of sporadic basal-like breast cancers is an area of active research. Epidemiologic studies illustrate a high prevalence of triple-negative breast cancers among younger women and those of African descent. Increasing evidence suggests that the risk factor profile differs between this subtype and the more common luminal subtypes. Although sensitive to chemotherapy, early relapse is common and a predilection for visceral metastasis, including brain metastasis, is seen. Targeted agents, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and poly (ADP-ribose) polymerase (PARP) inhibitors, are currently in clinical trials and hold promise in the treatment of this aggressive disease.
Classification of prostate cancer using a protease activity nanosensor library (2018)

Improved biomarkers are needed for prostate cancer, as the current gold standards have poor predictive value. Tests for circulating prostate-specific antigen (PSA) levels are susceptible to various noncancer comorbidities in the prostate and do not provide prognostic information, whereas physical biopsies are invasive, must be performed repeatedly, and only sample a fraction of the prostate. Injectable biosensors may provide a new paradigm for prostate cancer biomarkers by querying the status of the prostate via a noninvasive readout. Proteases are an important class of enzymes that play a role in every hallmark of cancer; their activities could be leveraged as biomarkers. We identified a panel of prostate cancer proteases through transcriptomic and proteomic analysis. Using this panel, we developed a nanosensor library that measures protease activity in vitro using fluorescence and in vivo using urinary readouts. In xenograft mouse models, we applied this nanosensor library to classify aggressive prostate cancer and to select predictive substrates. Last, we coformulated a subset of nanosensors with integrin-targeting ligands to increase sensitivity. These targeted nanosensors robustly classified prostate cancer aggressiveness and outperformed PSA. This activity-based nanosensor library could be useful throughout clinical management of prostate cancer, with both diagnostic and prognostic utility.
The microbial mimic poly IC induces durable and protective CD4+T cell immunity together with a dendritic cell targeted vaccine (2008)

CD4(+) Th1 type immunity is implicated in resistance to global infectious diseases. To improve the efficacy of T cell immunity induced by human immunodeficiency virus (HIV) vaccines, we are developing a protein-based approach that directly harnesses the function of dendritic cells (DCs) in intact lymphoid tissues. Vaccine proteins are selectively delivered to DCs by antibodies to DEC-205/CD205, a receptor for antigen presentation. We find that polyriboinosinic:polyribocytidylic acid (poly IC) independently serves as an adjuvant to allow a DC-targeted protein to induce protective CD4(+) T cell responses at a mucosal surface, the airway. After two doses of DEC-targeted, HIV gag p24 along with poly IC, responder CD4(+) T cells have qualitative features that have been correlated with protective function. The T cells simultaneously make IFN-gamma, tumor necrosis factor (TNF)-alpha, and IL-2, and in high amounts for prolonged periods. The T cells also proliferate and continue to secrete IFN-gamma in response to HIV gag p24. The adjuvant role of poly IC requires Toll-like receptor (TLR) 3 and melanoma differentiation-associated gene-5 (MDA5) receptors, but its analog poly IC(12)U requires only TLR3. We suggest that poly IC be tested as an adjuvant with DC-targeted vaccines to induce numerous multifunctional CD4(+) Th1 cells with proliferative capacity.
Down-regulation of the transporter for antigen presentation, proteasome subunits, and class I major histocompatibility complex in tumor cell lines. (1998)

Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In this study, reverse transcription-PCR was used to assess the expression in human tumor cell lines of mRNA for multiple components of the class I MHC antigen-processing pathway, including several proteasome subunits that have been implicated in antigen processing but have not been previously examined in this context (e.g., low molecular weight polypeptide proteasome subunit (LMP) 10, proteasome activator (PA) 28alpha, and PA28beta). Deficiencies in the expression of antigen-processing genes were demonstrated in 9 of 27 cell lines, representing a variety of histological types. In some cases, virtually complete deficiencies were observed in the expression of the four genes encoded within the MHC (TAP1, TAP2, LMP2, and LMP7), as well as LMP10, which is encoded outside the MHC. Combined deficiencies of these gene products were common, and marked deficiency of LMP10 was found in five of the nine cell lines with deficits. The existence of deficiencies in the expression of genes at dispersed loci suggested that the basis for the deficiencies was a regulatory mechanism, as opposed to mutation or deletion of these genes. Furthermore, most of the deficiencies were reversed by treatment with IFN-gamma. In contrast to such extreme deficiencies, we found unaltered or only partially decreased expression of PA28alpha and PA28beta in tumor cell lines. Thus, tumors may evade immune surveillance by simultaneously down-regulating multiple components of the MHC-I antigen-processing pathway, thereby altering the processing and presentation of tumor antigens. Expression of essential proteasome subunits, however, may still be maintained.
NMR Solution Structure and Receptor Peptide Binding of the CC Chemokine Eotaxin-2, (2000)

The human CC chemokine eotaxin-2 is a specific agonist for the chemokine receptor CCR3 and may play a role in the recruitment of eosinophils in allergic diseases and parasitic infections. We report the solution structure of eotaxin-2 determined using heteronuclear and triple resonance NMR methods. A family of 20 structures was calculated by hybrid distance geometry-simulated annealing from 854 NOE distance restraints, 48 dihedral angle restraints, and 12 hydrogen bond restraints. The structure of eotaxin-2 (73 amino acid residues) consists of a helical turn (residues 17-20) followed by a 3-stranded antiparallel beta-sheet (residues 22-26, 37-41, and 44-49) and an alpha-helix (residues 54-66). The N-loop (residues 9-16) is packed against both the sheet and the helix with the two conserved disulfide bonds tethering the N-terminal/N-loop region to the beta-sheet. The average backbone and heavy atom rmsd values of the 20 structures (residues 7-66) are 0.52 and 1.13 A, respectively. A linear peptide corresponding to the N-terminal region of CCR3 binds to eotaxin-2, inducing concentration-dependent chemical shift changes or line broadening of many residues. The distribution of these residues suggests that the peptide binds into an extended groove located at the interface between the N-loop and the beta2-beta3 hairpin. The receptor peptide may also interact with the N-terminus of the chemokine and part of the alpha-helix. Comparison of the eotaxin-2 structure with those of related chemokines indicates several structural features that may contribute to receptor specificity.
Presence Information Data Format (PIDF) (2004)

This memo specifies CPIM Presence Information Data Format (PIDF) as a
common presence data format for CPIM-compliant IM/Presence protocols.