gebhart/patrepeval huggingface dataset:
Matrilysin expression in human prostate carcinoma (1996)

The metalloproteinases, a multigene family of metal-requiring enzymes, have been suggested to play a role in tumor invasion and metastasis. Previously, we demonstrated that human primary prostate tumors express higher levels of matrilysin and gelatinase A mRNA than normal prostate does. In the study presented here, we used in situ hybridization and immunohistochemical staining of serial sections of paraffin-embedded primary prostate tumors to compare the sites of matrilysin and gelatinase A expression and protein localization. These results confirmed the epithelial nature of matrilysin expression and protein localization. In contrast, gelatinase A mRNA was localized to the interstitial stroma, whereas the protein was associated with the epithelial tumor cells. In situ hybridization was also used to demonstrate that gelatinase B expression was restricted to macrophages infiltrating the tumors. Proteins isolated from an additional set of frozen tumor specimens were analyzed by western blotting to determine the relative amounts of matrilysin in the active and proenzyme forms. The western analyses demonstrated that in all cases in which matrilysin was detected, at least some of the enzyme was in the active form. These results are discussed with respect to the possible role these enzymes may play in prostate tumor progression. © 1996 Wiley-Liss, Inc.
Topology simplification for polygonal virtual environments (1998)

We present a topology simplifying approach that can be used for genus reductions, removal of protuberances, and repair of cracks in polygonal models in a unified framework. Our work is complementary to the existing work on geometry simplification of polygonal datasets and we demonstrate that using topology and geometry simplifications together yields superior multiresolution hierarchies than is possible by using either of them alone. Our approach can also address the important issue of repair of cracks in polygonal models, as well as for rapid identification and removal of protuberances based on internal accessibility in polygonal models. Our approach is based on identifying holes and cracks by extending the concept of /spl alpha/-shapes to polygonal meshes under the L/sub /spl infin// distance metric. We then generate valid triangulations to fill them using the intuitive notion of sweeping an L/sub /spl infin// cube over the identified regions.
Hematological and biochemical action of tiazofurin (NSC 286193) in a case of refractory acute myeloid leukemia. (1987)

A patient with refractory acute myeloid leukemia was treated with tiazofurin, an agent that causes inhibition of tumor cell proliferation by depressing GTP concentrations in the malignant cells. The initial dose of 1100 mg/m2 was ineffective clinically and biochemically. Dose escalations to 1650, 2200, and finally 3300 mg/m2 resulted in a marked decrease in the absolute number of blasts without causing bone marrow hypoplasia or marked neutropenia. The decrease in the peripheral blast cell count was observed subsequent to a decline in GTP concentrations in the leukemic cells to less than 30% of the pretreatment value. Consecutive bone marrow examinations showed a remarkable shift from myeloblasts to more mature myeloid elements, suggesting an in vivo differentiative action of tiazofurin. Although a total dose of 23,650 mg/m2 was administered over a 13-day period, only very mild side effects were noted. The absence of complications reported by others in Phase I trials with tiazofurin may be related to our slow administration of the drug by pump over a 1-h period in this trial. Tiazofurin appears to be a promising agent in the treatment of leukemia because of its selective action on leukemic cells and the availability of a rapid in vitro method capable of predicting sensitivity of leukemic cells to the agent and monitoring its activity during treatment by measuring thiazole-4-carboxamide adenine dinucleotide and GTP concentrations. These observations are being tested in a larger group of leukemic patients.
Nicotinic Receptor Function in Schizophrenia (1996)

Schizophrenia can be partially characterized by deficits in sensory processing. Biochemical, molecular, and genetic studies of one such endophenotype, the P50 auditory-evoked potential gating deficit, suggest that one of the neuronal nicotinic receptors, the alpha 7 nicotinic receptor, may function in an inhibitory neuronal pathway involved in this phenotype. The P50 deficit is normalized in nongating subjects by nicotine. Although most schizophrenia patients are heavy smokers, the effects of nicotine may be transient, as alpha 7 receptors are known to desensitize rapidly. In an animal model of the P50 gating deficit, antagonists of the alpha 7 nicotinic receptor block normal gating of the second of paired auditory stimuli. Regional localization of receptor expression includes areas known to function in sensory filtering. An inhibitory mechanism, in the hippocampus, may involve nicotinic stimulation of gamma-aminobutyric acid (GABA)ergic interneurons, resulting in decreased response to repetitive stimuli. Expression of the alpha 7 receptor is decreased in hippocampal brain tissue, dissected postmortem, from schizophrenia subjects. The P50 deficit is inherited in schizophrenia pedigrees, but it is not sufficient for disease development and thus represents a predisposition factor. Linkage analysis between the P50 deficit in multiplex schizophrenia pedigrees and deoxyribonucleic acid (DNA) markers throughout the genome yielded positive lod scores to DNA markers mapping to a region of chromosome 15 containing the alpha 7 nicotinic receptor gene. Elucidation of possible interactions of the P50 with other factors, known to be important in the etiology of the disease, is important in determining an overall pathobiology of schizophrenia.
Amitriptyline versus Bupivacaine in Rat Sciatic Nerve Blockade (2001)

Amitriptyline is a more potent blocker of neuronal Na+ channels than bupivacaine in vivo and in vitro. These findings suggest that amitriptyline could extend its clinical usefulness for peripheral nerve blockade.
Health‐beneficial effects of probiotics: Its mode of action (2009)

It is now widely recognized that probiotics have health-beneficial effects on humans and animals. Probiotics should survive in the intestinal tract to exert beneficial effects on the host's health. To keep a sufficient level of probiotic bacteria in the gastrointestinal tract, a shorter interval between doses may be required. Although adherence to the intestinal epithelial cell and mucus is not a universal property of probiotics, high ability to adhere to the intestinal surface might strongly interfere with infection of pathogenic bacteria and regulate the immune system. The administration of probiotic Lactobacillus stimulated indigenous Lactobacilli and the production of short-chain fatty acids. This alteration of the intestinal environment should contribute to maintain the host's health. The immunomodulatory effects of probiotics are related to important parts of their beneficial effects. Probiotics may modulate the intestinal immune response through the stimulation of certain cytokine and IgA secretion in intestinal mucosa. The health-beneficial effects, in particular the immunomodulation effect, of probiotics depend on the strain used. Differences in indigenous intestinal microflora significantly alter the magnitude of the effects of a probiotic. Specific probiotic strains suitable for each animal species and their life stage as well as each individual should be found.
A model for efficient and flexible image computing (1994)

As common as imaging operations are, the literature contains little about how to build systems for image computation. This paper presents a system which addresses the major issues of image computing. The system includes an algorithm for performing imaging operations which guarantees that we only compute those regions of the image that will affect the result. The paper also discusses several other issues critical when creating a flexible image computing environment and describes solutions for these problems in the context of our model. These issues include how one handles images of any resolution and how one works in arbitrary coordinate systems. It also includes a discussion of the standard memory models, a presentation of a new model, and a discussion of each one's advantages and disadvantages.
Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth (2004)

Receptor tyrosine kinases of the Eph family are up-regulated in different types of cancer. EphB4 and its ligand ephrin-B2 have been linked to breast cancer, but little is known about how this receptor-ligand complex may contribute to oncogenesis. The Eph receptors transmit forward signals via their kinase domain and reverse signals via their transmembrane ephrin-B ligands. Therefore, we used EphB4 that were lacking the kinase domain and tagged with EGFP (EphB4 Delta C-EGFP) to differentiate between EphB4 and ephrin-B2 signaling. Interestingly, we found that expression of EphB4 Delta C-EGFP in breast cancer cells increases tumor growth in a mouse xenograft model. Given the undetectable EphB4 activation in the tumor cells, dominant negative effects of EphB4 Delta C-EGFP are unlikely to explain the increased tumor growth. Examination of the tumors revealed that ephrin-B2 is primarily expressed in the vasculature and that the EphB4 Delta C-EGFP tumors have a higher blood content than control tumors, concomitant with increased size of blood vessels. In support of an effect on the vasculature, the extracellular domain of EphB4 attracts endothelial cells in vitro and stimulates endothelial cell invasion, survival, and proliferation, all crucial factors for angiogenesis. These results support a model in which EphB4 promotes tumor growth by stimulating angiogenesis through ephrin-B2.
Preparation of alkenes: a practical approach (1997)

1: Introducton and general methods. 2: The Wittig reaction and related methods. 3: Non-phosphorus stabilised carbanions in alkene synthesis. 4: Chromium - and titanium-mediated synthesis of alkenes from carbonyl compounds. 5: Elimination and addition-elimination reactions. 6: Reduction of alkynes. 7: Reactiotn of alkynes with organometallic reagents. 8: Catalytic coupling reactions. 9: Summary of alkene synthesis. Appendix 1: Summary of Protocols (affording alkenes). Appendix 2: List of suppliers. Index
Frequent loss of heterozygosity at 7q31.1 in primary prostate cancer is associated with tumor aggressiveness and progression. (1995)

Cytogenetic analyses have demonstrated that chromosome region 7q22-32 is commonly altered in prostate adenocarcinomas. In addition, in recent fluorescence in situ hybridization studies, we have observed that aneusomy of chromosome 7 is frequent in prostate cancer and is associated with higher tumor grade, advanced pathological stage, and early prostate cancer death. These findings suggest that genetic alterations of chromosome 7 play a significant role in the development of prostate cancer. To better define the chromosome 7 alterations, PCR analysis of 21 microsatellite loci was performed on 54 paired prostate cancer and control DNAs. Overall, chromosome 7 allelic imbalance was identified in 16 of 54 cases (30%). Allelic imbalances of loci mapped to 7q were observed in 15 of the 16 cases. The allelic imbalances were classified as losses in 15 tumors (28%) and as gains in 1 (2%) by comparative multiplex PCR analysis. The most common site of allelic loss included loci D7S523 and D7S486 at 7q31.1. A comparison with clinicopathological features of the tested tumors revealed that the allelic loss of 7q31.1 correlated with higher tumor grade (P = 0.012) and lymph node metastasis (P = 0.017). These results indicate that 7q31 may be the site of a putative suppressor gene(s) important for the pathogenesis of prostate carcinoma, and that the genetic alterations at 7q31.1 may participate in tumor progression and metastasis.
Inhibition of Activity-Dependent Arc Protein Expression in the Rat Hippocampus Impairs the Maintenance of Long-Term Potentiation and the Consolidation of Long-Term Memory (2000)

It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEG Arc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995). Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.
AT-AC Pre-mRNA Splicing Mechanisms and Conservation of Minor Introns in Voltage-Gated Ion Channel Genes (1999)

Shortly after the discovery of split genes in 1977, a conserved sequence feature at both ends of cellular and viral introns was recognized, i.e., the presence of GT at the 5′ splice site and AG at the 3′ splice site, giving rise to the so-called GT-AG rule (8). This rule holds in most cases, but exceptions have been found. For example, GC is occasionally found at the 5′ end of certain introns (Table ​(Table1)1) (38). GC-AG introns are processed by the same splicing pathway as conventional GT-AG introns (3). It had long been assumed that removal of all introns from eukaryotic pre-mRNAs took place by the same splicing pathway, until recent developments demonstrated the existence of a second pre-mRNA splicing pathway. 



TABLE 1

Compilation of GC-AG intronsa 



Intron 6 of the gene encoding human P120, a proliferating cell nucleolar antigen, and intron 7 of the gene encoding human CMP, a cartilage matrix protein (matrilin 1), were the first reported examples of introns with AT and AC at the intron ends, instead of GT and AG (38). Intron 6 of the gene encoding Rep-3, a DNA repair protein, and intron 2 of the gene encoding Prospero, a Drosophila melanogaster homeodomain transcription factor, also have AT-AC ends (28). In addition to their distinctive dinucleotide ends, these and other AT-AC introns have highly conserved 5′-splice-site and presumptive branch site 8-nucleotide sequence elements that are not present in the major class of introns, ATATCCTY and TCCTTRAY, respectively. On the basis of these sequence features, it was proposed that the minor U11 and U12 snRNAs, which have regions of complementarity to these elements, are required for splicing of AT-AC introns (28). Important aspects of this prediction were soon verified experimentally (29, 100), and two additional minor snRNAs involved in the novel pre-mRNA splicing pathway were discovered (101).

The AT-AC splicing pathway was originally named after the distinctive sequences of the intron ends (100). It was later found that a few introns with AT-AC ends are processed by the major pathway (120) and, conversely, that some introns with GT-AG ends are spliced by the minor pathway (18). Therefore, the name AT-AC no longer reflects the dinucleotide intron ends per se, but rather it refers to the minor pathway itself. An alternative designation for the two pathways—U2 dependent and U12 dependent—reflects their observed or expected requirements for one of the four snRNAs specific to each pathway (86).
Sound Pressure Generated in an External-Ear Replica and Real Human Ears by a Nearby Point Source (1968)

A rubber replica has a pinna, concha, and auditory meatus with dimensions comparable with those of real human ears. At the eardrum position, there is provision for a totally reflecting termination (hard wall) or for various eardrum impedance networks. The replica is mounted in a rigid plane, and a point source at a distance of 8 cm provides sound with various angles of incidence over the frequency range 1–15 kHz. The sound pressure is measured with a probe-tube microphone at selected positions in the open canal and at the center of a plug closing the ear-canal entrance (“meatus-blocked” condition). The response with open canal and the response with blocked meatus have virtually identical angular dependence up to 12 kHz. From 2–7 kHz, there is substantial acoustic gain at the eardrum position associated with a fundamental canal resonance (M1) and a second mode largely controlled by a depth resonance of the concha (M2). Pressure distributions in the canal and concha are given for M1, M2, and three other modes. Limited data for six real ears with open and blocked canal are in good agreement with replica measurements up to 7 kHz. At 8 kHz, however, the on-axis response of real ears passes through a sharp minimum that is either removed to a higher frequency or is largely absent with the sound source above the axis.
Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis (2008)

Apelin and its cognate G protein-coupled receptor APJ constitute a signaling pathway with a positive inotropic effect on cardiac function and a vasodepressor function in the systemic circulation. The apelin-APJ pathway appears to have opposing physiological roles to the renin-angiotensin system. Here we investigated whether the apelin-APJ pathway can directly antagonize vascular disease-related Ang II actions. In ApoE-KO mice, exogenous Ang II induced atherosclerosis and abdominal aortic aneurysm formation; we found that coinfusion of apelin abrogated these effects. Similarly, apelin treatment rescued Ang II-mediated increases in neointimal formation and vascular remodeling in a vein graft model. NO has previously been implicated in the vasodepressor function of apelin; we found that apelin treatment increased NO bioavailability in ApoE-KO mice. Furthermore, infusion of an NO synthase inhibitor blocked the apelin-mediated decrease in atherosclerosis and aneurysm formation. In rat primary aortic smooth muscle cells, apelin inhibited Ang II-mediated transcriptional regulation of multiple targets as measured by reporter assays. In addition, we demonstrated by coimmunoprecipitation and fluorescence resonance energy transfer analysis that the Ang II and apelin receptors interacted physically. Taken together, these findings indicate that apelin signaling can block Ang II actions in vascular disease by increasing NO production and inhibiting Ang II cellular signaling.
Tear Glucose Dynamics in Diabetes Mellitus (2006)

This study compares tear glucose dynamic differences between 121 diabetic and nondiabetic subjects after the administration of a carbohydrate load. A quantitative chromatographic analysis of tear glucose was used and the values correlated to blood glucose values. Diabetic and nondiabetic tear glucose mean values were 0.35 +/- 0.04 mmol/L and 0.16 +/- 0.03 mmol/L, respectively. Significant differences were observed among the subject groups in both the tear and capillary blood glucose values. A correlation between tear glucose and capillary blood glucose was observed. The concentration of glucose in the tear fluid changes proportionately with respect to capillary blood glucose after a carbohydrate challenge. Although it is possible to determine the diabetic status of a subject using tear glucose values alone, in the clinical setting this may not prove to be practical due to technical limitations.
Bifunctional Ag@Pd-Ag Nanocubes for Highly Sensitive Monitoring of Catalytic Reactions by Surface-Enhanced Raman Spectroscopy (2015)

We report a route to the facile synthesis of Ag@Pd-Ag nanocubes by cotitrating Na2PdCl4 and AgNO3 into an aqueous suspension of Ag nanocubes at room temperature in the presence of ascorbic acid and poly(vinylpyrrolidone). With an increase in the total titration volume, we observed the codeposition of Pd and Ag atoms onto the edges, corners, and side faces of the Ag nanocubes in a site-by-site fashion. By maneuvering the Pd/Ag ratio, we could optimize the SERS and catalytic activities of the Ag@Pd-Ag nanocubes for in situ SERS monitoring of the Pd-catalyzed reduction of 4-nitrothiophenol by NaBH4.
Lipoxygenase Is Involved in the Control of Potato Tuber Development (2001)

Plant lipoxygenases (LOXs) are a functionally diverse class of dioxygenases implicated in physiological processes such as growth, senescence, and stress-related responses. LOXs incorporate oxygen into their fatty acid substrates and produce hydroperoxide fatty acids that are precursors of jasmonic acid and related compounds. Here, we report the involvement of the tuber-associated LOXs, designated the Lox1 class, in the control of tuber growth. RNA hybridization analysis showed that the accumulation of Lox1 class transcripts was restricted to developing tubers, stolons, and roots and that mRNA accumulation correlated positively with tuber initiation and growth. In situ hybridization showed that Lox1 class transcripts accumulated in the apical and subapical regions of the newly formed tuber, specifically in the vascular tissue of the perimedullary region, the site of the most active cell growth during tuber enlargement. Suppression mutants produced by expressing antisense coding sequence of a specific tuber LOX, designated POTLX-1, exhibited a significant reduction in LOX activity in stolons and tubers. The suppression of LOX activity correlated with reduced tuber yield, decreased average tuber size, and a disruption of tuber formation. Our results indicate that the pathway initiated by the expression of the Lox1 class genes of potato is involved in the regulation of tuber enlargement.
Tapered Conical Polymer Microneedles Fabricated Using an Integrated Lens Technique for Transdermal Drug Delivery (2007)

Administration of protein and DNA biotherapeutics is limited by the need for hypodermic injection. Use of micron-scale needles to deliver drugs in a minimally invasive manner provides an attractive alternative, but application of this approach is limited by the need for suitable microneedle designs and fabrication methods. To address this need, this paper presents a conical polymer microneedle design that is fabricated using a novel integrated lens technique and analyzed for its ability to insert into the skin without mechanical failure. Microneedle master structures were fabricated using microlenses etched into a glass substrate that focused light through SU-8 negative epoxy resist to produce sharply tapered structures. Microneedle replicates were fabricated out of biodegradable polymers by micromolding. Because microneedle mechanical properties are critical to their insertion into the skin, we theoretically modeled two failure modes (axial mode and transverse mode), and analytical models were compared with measured data showing general agreement. Guided by this analysis, polymer microneedles were designed and demonstrated to insert to different depths into porcine skin in vitro. "Long" polymer microneedles were also demonstrated in human subjects to insert deeply without failure.