gebhart/patrepeval huggingface dataset:
Cytomorphology of Circulating Colorectal Tumor Cells: A Small Case Series (2010)

Several methodologies exist to enumerate circulating tumor cells (CTCs) from the blood of cancer patients; however, most methodologies lack high-resolution imaging, and thus, little is known about the cytomorphologic features of these cells. In this study of metastatic colorectal cancer patients, we used immunofluorescent staining with fiber-optic array scanning technology to identify CTCs, with subsequent Wright-Giemsa and Papanicolau staining. The CTCs were compared to the corresponding primary and metastatic tumors. The colorectal CTCs showed marked intrapatient pleomorphism. In comparison to the corresponding tissue biopsies, cells from all sites showed similar pleomorphism, demonstrating that colorectal CTCs retain the pleomorphism present in regions of solid growth. They also often retain particular cytomorphologic features present in the patient's primary and/or metastatic tumor tissue. This study provides an initial analysis of the cytomorphologic features of circulating colon cancer cells, providing a foundation for further investigation into the significance and metastatic potential of CTCs.
LFG : An anti-apoptotic gene that provides protection from Fas-mediated cell death (1999)

Programmed cell death regulates a number of biological phenomena, and the apoptotic signal must itself be tightly controlled to avoid inappropriate cell death. We established a genetic screen to search for molecules that inhibit the apoptotic signal from the Fas receptor. Here we report the isolation of a gene, LFG, that protects cells uniquely from Fas but not from the mechanistically related tumor necrosis factor alpha death signal. LFG is widely distributed, but remarkably is highly expressed in the hippocampus. LFG can bind to the Fas receptor, but does not regulate Fas expression or interfere with binding of an agonist antibody. Furthermore LFG does not inhibit binding of FADD to Fas.
Deletion of vanilloid receptor 1_expressing primary afferent neurons for pain control (2004)

Control of cancer, neuropathic, and postoperative pain is frequently inadequate or compromised by debilitating side effects. Inhibition or removal of certain nociceptive neurons, while retaining all other sensory modalities and motor function, would represent a new therapeutic approach to control severe pain. The enriched expression of transient receptor potential cation channel, subfamily V, member 1 (TRPV1; also known as the vanilloid receptor, VR1) in nociceptive neurons of the dorsal root and trigeminal ganglia allowed us to test this concept. Administration of the potent TRPV1 agonist resiniferatoxin (RTX) to neuronal perikarya induces calcium cytotoxicity by opening the TRPV1 ion channel and selectively ablates nociceptive neurons. This treatment blocks experimental inflammatory hyperalgesia and neurogenic inflammation in rats and naturally occurring cancer and debilitating arthritic pain in dogs. Sensations of touch, proprioception, and high-threshold mechanosensitive nociception, as well as locomotor function, remained intact in both species. In separate experiments directed at postoperative pain control, subcutaneous administration of RTX transiently disrupted nociceptive nerve endings, yielding reversible analgesia. In human dorsal root ganglion cultures, RTX induced a prolonged increase in intracellular calcium in vanilloid-sensitive neurons, while leaving other, adjacent neurons unaffected. The results suggest that nociceptive neuronal or nerve terminal deletion will be effective and broadly applicable as strategies for pain management.
Foreground and background interaction with sensor-enhanced mobile devices (2005)

Building on Buxton's foreground/background model, we discuss the importance of explicitly considering both foreground interaction and background interaction, as well as transitions between foreground and background, in the design and implementation of sensing techniques for sensor-enhanced mobile devices. Our view is that the foreground concerns deliberate user activity where the user is attending to the device, while the background is the realm of inattention or split attention, using naturally occurring user activity as an input that allows the device to infer or anticipate user needs. The five questions for sensing systems of Bellotti et al. [2002] proposed as a framework for this special issue, primarily address the foreground, but neglect critical issues with background sensing. To support our perspective, we discuss a variety of foreground and background sensing techniques that we have implemented for sensor-enhanced mobile devices, such as powering on the device when the user picks it up, sensing when the user is holding the device to his ear, automatically switching between portrait and landscape display orientations depending on how the user is holding the device, and scrolling the display using tilt. We also contribute system architecture issues, such as using the foreground/background model to handle cross-talk between multiple sensor-based interaction techniques, and theoretical perspectives, such as a classification of recognition errors based on explicitly considering transitions between the foreground and background. Based on our experiences, we propose design issues and lessons learned for foreground/background sensing systems.
Molecular Profiling of Matched Samples Identifies Biomarkers of Papillary Thyroid Carcinoma Lymph Node Metastasis (2007)

Biomarkers of papillary thyroid carcinoma (PTC) metastasis can accurately identify metastatic cells and aggressive tumor behavior. To find new markers, serial analysis of gene expression (SAGE) was done on three samples from the same patient: normal thyroid tissue, primary PTC, and a PTC lymph node metastasis. This genomewide expression analysis identified 31 genes expressed in lymph node metastasis, but not in the primary tumor. Eleven genes were evaluated by quantitative real-time reverse transcription-PCR (qPCR) on independent sets of matched samples to find genes that were consistently different between the tumor and metastatic samples. LIMD2 and PTPRC (CD45) showed a statistically significant difference in expression between tumor and metastatic samples (P < 0.0045), and an additional gene (LTB) had borderline significance. PTPRC and LTB were tested by immunohistochemistry in an independent set of paired samples, with both markers showing a difference in protein expression. All 20 metastases from 6 patients showed expression in both markers, with little or no expression in primary tumor. Some of these markers could provide an improved means to detect metastatic PTC cells during initial staging of a newly diagnosed carcinoma and/or to rule out recurrence. The functional role of these genes may also provide insight into mechanisms of thyroid cancer metastasis.
Differential Gene Regulation by the Two Progesterone Receptor Isoforms in Human Breast Cancer Cells (2002)

The PR-A and PR-B isoforms of progesterone receptors (PR) have different physiological functions, and their ratio varies widely in breast cancers. To determine whether the two PR regulate different genes, we used human breast cancer cell lines engineered to express one or the other isoform. Cells were treated with progesterone in triplicate, time-separated experiments, allowing statistical analyses of microarray gene expression data. Of 94 progesterone-regulated genes, 65 are uniquely regulated by PR-B, 4 uniquely by PR-A, and only 25 by both. Almost half the genes encode proteins that are membrane-bound or involved in membrane-initiated signaling. We also find an important set of progesterone-regulated genes involved in mammary gland development and/or implicated in breast cancer. This first, large scale study of PR gene regulation has important implications for the measurement of PR in breast cancers and for the many clinical uses of synthetic progestins. It suggests that it is important to distinguish between the two isoforms in breast cancers and that isoform-specific genes can be used to screen for ligands that selectively modulate the activity of PR-A or PR-B. Additionally, use of natural target genes, rather than "consensus" response elements, for transcription studies should improve our understanding of steroid hormone action.
Partial liquid ventilation (2006)

Evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers.
Short Interfering RNA Guide Strand Modifiers from Computational Screening (2013)

Short interfering RNAs (siRNAs) are promising drug candidates for a wide range of targets including those previously considered "undruggable". However, properties associated with the native RNA structure limit drug development, and chemical modifications are necessary. Here we describe the structure-guided discovery of functional modifications for the guide strand 5'-end using computational screening with the high-resolution structure of human Ago2, the key nuclease on the RNA interference pathway. Our results indicate the guide strand 5'-end nucleotide need not engage in Watson-Crick (W/C) H-bonding but must fit the general shape of the 5'-end binding site in MID/PIWI domains of hAgo2 for efficient knockdown. 1,2,3-Triazol-4-yl bases formed from the CuAAC reaction of azides and 1-ethynylribose, which is readily incorporated into RNA via the phosphoramidite, perform well at the guide strand 5'-end. In contrast, purine derivatives with modified Hoogsteen faces or N2 substituents are poor choices for 5'-end modifications. Finally, we identified a 1,2,3-triazol-4-yl base incapable of W/C H-bonding that performs well at guide strand position 12, where base pairing to target was expected to be important. This work expands the repertoire of functional nucleotide analogues for siRNAs.
Investigation into the Reactivity of Unsupported and Supported Ag7and Ag8Clusters with Toxic Metal Ions (2011)

We report the chemical interactions of unsupported and alumina-supported Ag(7) and Ag(8) clusters protected with MSA (mercaptosuccinic acid) with heavy metal ions Hg(II), Cd(II), and Pb(II) in water at different concentrations. The investigation was carried out to determine the feasibility of this interesting new class of materials called quantum clusters for water purification. These systems were studied using various spectroscopic and microscopic techniques such as ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering, zeta potential measurements, scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and photoluminescence spectroscopy and in detail by X-ray photoelectron spectroscopy. We observed that the metal ions interact with both the silver atoms of the clusters and the functional groups of the capping agent (MSA). The mercuric ions were reduced to metallic mercury by both supported and unsupported clusters, due to the feasibility of the redox reaction, whereas no reduction was observed for Cd(II) and Pb(II). As a result of the interaction, the luminescence of the cluster is lost which can be used to sense Hg(II). At lower concentrations, the metal ions were chemically bonded to the carboxylate groups of MSA. Absence of reduction of Hg(II) at lower concentration is due to the chemical affinity of the ligands and the lower silver content per cluster compared to the number of carboxylate groups.
Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. (1993)

Patients with unstable angina have an increased expression of granulocyte and monocyte CD11b/CD18 adhesion receptors, indicating that an inflammatory reaction takes place within their coronary tree. Activation of these leukocytes may induce coronary vasoconstriction, favor thrombotic processes, and further activate platelets, thus having potential implications on the pathogenesis of unstable coronary artery disease.
EuroTracker® dyes: design, synthesis, structure and photophysical properties of very bright europium complexes and their use in bioassays and cellular optical imaging (2014)

The development of the brightest luminescent europium(iii) complexes is traced, including analysis of the C3-symmetric core complex based on a functionalized triazacyclononane and identification of the most suitable strongly absorbing chromophore. Strategies for the synthesis of the complexes, including enantiopure analogues, are outlined and opportunities for applications in time-resolved microscopy and spectral imaging emphasised. Practicable examples are introduced, including selective organelle staining for cellular optical imaging at 65 nm resolution and the development of new bioassays using time-resolved FRET methods.
Motion: Representation and perception (1986)

This book presents the papers on image processing. Topics considered include computer vision, motion and time-varying imagery, tracking three-dimensional moving light displays, determining motion parameters for scenes with translation and rotation, determining 3-D motion parameters of a rigid body, a hybrid approach to structure-from-motion, and multicomputer architectures for real-time perception.
Hepatic electrical stimulation reduces blood glucose in diabetic rats (2010)

Hepatic electrical stimulation is capable of reducing both fasting and fed blood glucose in normal, and type 1 and type 2 diabetic rats and the effect may be partially mediated via an increase in GLP-1 release.
Matrix Metalloproteinases As Novel Biomarker s and Potential Therapeutic Targets in Human Cancer (2009)

The matrix metalloproteinase (MMP) family of enzymes is comprised of critically important extracellular matrix remodeling proteases whose activity has been implicated in a number of key normal and pathologic processes. The latter include tumor growth, progression, and metastasis as well as the dysregulated angiogenesis that is associated with these events. As a result, these proteases have come to represent important therapeutic and diagnostic targets for the treatment and detection of human cancers. In this review, we summarize the literature that establishes these enzymes as important clinical targets, discuss the complexity surrounding their choice as such, and chronicle the development strategies and outcomes of their clinical testing to date. The status of the MMP inhibitors currently in US Food and Drug Administration approved clinical trials is presented and reviewed. We also discuss the more recent and successful targeting of this enzyme family as diagnostic and prognostic predictors of human cancer, its status, and its stage. This analysis includes a wide variety of human cancers and a number of human sample types including tissue, plasma, serum, and urine.
Evidence for the role of class I and class II HLA antigens in the lytic function of a cloned line of human natural killer cells. (1985)

Monoclonal antibodies with specificity for HLA class I and class II antigens were generated which either inhibit or enhance the lytic activity of a cloned line of human NK cells. These antibodies were obtained from a fusion with spleen cells from mice immunized with NK clone 3.3. They affect the lytic function of that clone at the level of the killer cell; additional evidence suggests that the effect takes place during an early stage of lysis. Immunoprecipitation and cross-clearing experiments using MHC antibodies of known specificity demonstrate the reactivity of mAbs 131 and 164 with HLA class I antigens and mAbs 210 and 273 with HLA class II antigens. Binding studies indicate that these antibodies are probably recognizing nonpolymorphic MHC determinants. Although these antibodies bind to other NK effector cells tested, they have no effect on the lytic function of these bulk NK populations. Preliminary studies, however, indicate that they do affect the NK activity of a proportion of the clones within these bulk populations. To further assess the potential role of HLA gene products in the lytic function of NK3.3, several well-defined anti-MHC antibodies were tested for their effects on NK3.3 function. The anti-HLA class I and class II antibodies could each be grouped into functional categories based on their ability to enhance, inhibit, or not affect the lysis of NK-sensitive targets K562 and MOLT-4 by NK clone 3.3. These results demonstrate, for the first time, a potential involvement of MHC molecules with NK function.
Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. (1994)

Numerous integral membrane proteins are degraded in the mammalian ER. HMG-CoA reductase (HMG-R), a key enzyme in the mevalonate pathway by which isoprenoids and sterols are synthesized, is one substrate of ER degradation. The degradation of HMG-R is modulated by feedback signals from the mevalonate pathway. We investigated the role of regulated degradation of the two isozymes of HMG-R, Hmg1p and Hmg2p, in the physiology of Saccharomyces cerevisiae. Hmg1p was quite stable, whereas Hmg2p was rapidly degraded. Degradation of Hmg2p proceeded independently of vacuolar proteases or secretory traffic, indicating that Hmg2p degradation occurred at the ER. Hmg2p stability was strongly affected by modulation of the mevalonate pathway through pharmacological or genetic means. Decreased mevalonate pathway flux resulted in decreased degradation of Hmg2p. One signal for degradation of Hmg2p was a nonsterol, mevalonate-derived molecule produced before the synthesis of squalene. Genetic evidence indicated that a farnesylated protein may also be necessary for Hmg2p degradation. Studies with reporter genes demonstrated that the stability of each isozyme was determined by its noncatalytic NH2-terminal domain. Our data show that ER protein degradation is widely conserved among eukaryotes, and that feedback control of HMG-R degradation is an ancient paradigm of regulation.
Geomechanical Evidence for Shear Failure of Chalk During Production of the Ekofisk Field (1991)

Abstract The Ekofisk Field is a naturally-fractured chalk reservoir in the Norwegian Sector of the North Sea that has been producing hydrocarbons for over 20 years. In situ stresses in the field have been constantly changing because of the decline in pore pressure that has occurred in the reservoir as a result of production. The effect of production and pore pressure drawdown on the minimum horizontal in situ stress in the Ekofisk Field has been determined from shut-in pressure data from 37 hydraulic fractures conducted during the past 15 years. The effective stresses in the reservoir increase linearly with pore pressure drawdown, but at different rates. The reservoir stress path, defined as the ratio of the change in effective minimum horizontal stress to the change in effective overburden stress, is approximately 0.20. Laboratory experiments, which simulate the stress path followed by reservoir rock during the production history of the field, show that shear failure has occurred during compaction of high porosity chalk as the shear stress increased with pore pressure drawdown. Shear failure during depletion will increase fracture density and reduce matrix block dimensions in the fractured reservoir, thereby maintaining reservoir permeability as the apertures of older natural fractures are closed with increasing deformation. It is suggested that the shear failure process may account for the continued good producibility of the Ekofisk Field, in spite of compaction.
CGP 41251 a Novel Protein Kinase Inhibitor with in vitro Selectivity for Protein Kinase C, Strongly Inhibits Immunological Activation of Human Skin Mast Cells and Human Basophils (1993)

The process of high-affinity IgE receptor (Fc epsilon RI)-mediated signal transduction in human basophils and mast cells is accompanied by activation of protein kinase C (PKC). The present study investigated the effects of a novel protein kinase inhibitor with in vitro selectivity for PKC (CGP 41251) in comparison with the potent but non-selective PKC inhibitor staurosporine on the activation of human peripheral basophilic leukocytes and enzymatically isolated human skin mast cells. CGP 41251 exerted strong concentration-dependent inhibitory effects on Fc epsilon RI-mediated histamine release from both cell populations. In addition, the IgE-mediated generation of arachidonic acid metabolites (leukotriene C4/D4 and prostaglandin E2) from human basophils was also significantly inhibited by this compound. Its action was not significantly different from the action of staurosporine. Direct activation of cellular PKC by the phorbol ester 12-o-tetradecanoyl-phorbol-13-acetate and subsequent histamine release from basophils was also inhibited by both compounds. CGP 41251 did not suppress N-formyl-met-leu-phe- or A23187-induced activation of basophils, whereas A23187-induced mediator release from human skin mast cells was inhibited in a concentration-dependent fashion. We conclude that an increase of in vitro selectivity for PKC does not significantly enhance inhibitory effects on immunological activation of histamine-containing cells. Moreover, nonimmunological pathways of signal transduction in basophils and mast cells appear to be mediated by distinct biochemical events.
Punctin, a Novel ADAMTS-like Molecule, ADAMTSL-1, in Extracellular Matrix (2002)

Punctin (ADAMTSL-1) is a secreted molecule resembling members of the ADAMTS family of proteases. Punctin lacks the pro-metalloprotease and the disintegrin-like domain typical of this family but contains other ADAMTS domains in precise order including four thrombospondin type I repeats. Punctin is the product of a distinct gene on human chromosome 9p21-22 and mouse chromosome 4 that is expressed in adult skeletal muscle. His-tagged punctin expressed in stably transfected High-Five(TM) insect cells was purified to apparent homogeneity by Ni-chromatography of conditioned medium. The NH(2) terminus is not blocked and has the sequence EEDRD and so forth as determined by Edman degradation, demonstrating signal peptidase processing. Recombinant epitope-tagged punctin has a calculated mass of 59,991 Da but exhibits major molecular species of 61970 +/- 6 Da and 62131 +/- 5 Da as measured by liquid chromatography electrospray mass spectrometry. Punctin is a glycoprotein based on carbohydrate staining and liquid chromatography electrospray mass spectrometry glycopeptide analysis. Glycosylation occurs at a single N-linked site as demonstrated by altered electrophoretic migration of punctin expressed in the presence of tunicamycin A. Punctin contains disulfide bonds based on antibody accessibility and electrophoretic migration under reducing versus nonreducing conditions. Rotary shadowing demonstrates that punctin is hatchet-shaped having a globular region attached to a short stem. In transfected COS-1 cells, punctin is deposited in the cell substratum in a punctate fashion and is excluded from focal contacts. Punctin is the first member of a novel family of ADAMTS-like proteins that may have important functions in the extracellular matrix.