gebhart/patrepeval huggingface dataset:
On the association of glycoprotein Ib and actin-binding protein in human platelets. (1985)

Glycoprotein (GP) Ib was purified from lysates of human platelets prepared in the presence or absence of inhibitors of the endogenous calcium-activated neutral protease (CANP) by immunoaffinity chromatography, employing the GPIb-specific murine monoclonal antibody, AP1, coupled to Sepharose CL4B. When derived from lysates prepared in the presence of EDTA or leupeptin, the eluate from the AP1-affinity column contained a 240,000-260,000-mol-wt protein in addition to GPIb. In SDS PAGE, this protein was stained by Coomassie Blue R, but not by the periodic acid-Schiff reagent, and it was not labeled with 125I in intact platelets by the lactoperoxidase-catalyzed method. When derived from lysates prepared in the absence of CANP inhibitors, the eluate contained only GPIb and its proteolytic derivative, glycocalicin. A change in the electrophoretic mobility of GPIb consistent with its association with the 240,000-260,000-mol-wt protein was confirmed by crossed immunoelectrophoresis. By an immunoblot technique involving transfer of proteins eluted from the AP1-affinity column and separated by SDS PAGE onto a nitrocellulose membrane, the 240,000-260,000-mol-wt protein bound polyclonal goat antibody raised against rabbit macrophage actin-binding protein (ABP). On the basis of these results, we conclude the GPIb is tightly associated with ABP under conditions in which the endogenous CANP is inhibited, and that this apparent transmembrane complex of GPIb-ABP can be isolated in lysates of nonactivated human platelets.
Nitric Oxide Modulates Mitochondrial Respiration in Failing Human Heart (1999)

Background-Our objective for this study was to investigate whether nitric oxide (NO) modulates tissue respiration in the failing human myocardium. Methods and Results-Left ventricular free wall and right ventricular tissue samples were taken from 14 failing explanted human hearts at the time of transplantation. Tissue oxygen consumption was measured with a Clark-type oxygen electrode in an airtight stirred bath containing Krebs solution buffered with HEPES at 37 degrees C (pH 7.4). Rate of decrease in oxygen concentration was expressed as a percentage of the baseline, and results of the highest dose are indicated. Bradykinin (10(-4) mol/L, -21+/-5%), amlodipine (10(-5) mol/L, -14+/-5%), the ACE inhibitor ramiprilat (10(-4) mol/L, -21+/-2%), and the neutral endopeptidase inhibitor thiorphan (10(-4) mol/L, -16+/-5%) all caused concentration-dependent decreases in tissue oxygen consumption. Responses to bradykinin (-2+/-6%), amlodipine (-2+/-4%), ramiprilat (-5+/-6%), and thiorphan (-4+/-7%) were significantly attenuated after NO synthase blockade with N-nitro-L-arginine methyl ester (10(-4) mol/L; all P<0.05). NO-releasing compounds S-nitroso-N-acetyl-penicillamine (10(-4) mol/L, -34+/-5%) and nitroglycerin (10(-4) mol/L, -21+/-5%), also decreased tissue oxygen consumption in a concentration-dependent manner. However, the reduction in tissue oxygen consumption in response to S-nitroso-N-acetyl-penicillamine (-35+/-7%) or nitroglycerin (-16+/-5%) was not significantly affected by N-nitro-L-arginine methyl ester. Conclusions-These results indicate that the modulation of oxygen consumption by both endogenous and exogenous NO is preserved in the failing human myocardium and that the inhibition of kinin degradation plays an important role in the regulation of mitochondrial respiration.
A molecular engineering toolbox for the structural biologist (2017)

Exciting new technological developments have pushed the boundaries of structural biology, and have enabled studies of biological macromolecules and assemblies that would have been unthinkable not long ago. Yet, the enhanced capabilities of structural biologists to pry into the complex molecular world have also placed new demands on the abilities of protein engineers to reproduce this complexity into the test tube. With this challenge in mind, we review the contents of the modern molecular engineering toolbox that allow the manipulation of proteins in a site-specific and chemically well-defined fashion. Thus, we cover concepts related to the modification of cysteines and other natural amino acids, native chemical ligation, intein and sortase-based approaches, amber suppression, as well as chemical and enzymatic bio-conjugation strategies. We also describe how these tools can be used to aid methodology development in X-ray crystallography, nuclear magnetic resonance, cryo-electron microscopy and in the studies of dynamic interactions. It is our hope that this monograph will inspire structural biologists and protein engineers alike to apply these tools to novel systems, and to enhance and broaden their scope to meet the outstanding challenges in understanding the molecular basis of cellular processes and disease.
Efficient Approach to Medium-sized Cyclic Molecules Containing (E)-Alkene via Z to E Photochemical Isomerization in the Presence of AgNO3-impregnated Silica Gel (2018)

Efficient synthesis of medium-sized cyclic molecules containing an (E)-alkene was performed via the highly (E)-selective photochemical isomerization of the (Z)-isomer, facilitated by AgNO3-impregnated silica gel. Efficient synthesis of medium-sized cyclic molecules containing an (E)-alkene were accomplished by highly (E)-selective photochemical isomerization of the (Z)-isomer facilitated by presence of AgNO3-impregnated silica gel.
Distinct Biological Roles for the Notch Ligands Jagged-1 and Jagged-2 (2009)

Notch signaling is activated in a subset of non-small cell lung cancer cells because of overexpression of Notch3, but the role of Notch ligands has not been fully defined. On the basis of gene expression profiling of a panel of non-small cell lung cancer cell lines, we found that the predominant Notch ligands were JAG1, JAG2, DLL1, and DLL3. Given that Notch ligands reportedly have overlapping receptor binding specificities, we postulated that they have redundant biological roles. Arguing against this hypothesis, we found that JAG1 and JAG2 were differentially regulated; JAG1 expression was dependent upon epidermal growth factor receptor (EGFR) activation in HCC827 cells, which require EGFR for survival, whereas JAG2 expression was EGFR-independent in these cells. Furthermore, HCC827 cells underwent apoptosis following depletion of JAG1 but not JAG2, whereas co-culture experiments revealed that depletion of JAG2, but not JAG1, enhanced the ability of HCC827 cells to chemoattract THP-1 human monocytes. JAG2-depleted HCC827 cells expressed high levels of inflammation-related genes, including interleukin 1 (IL1) and a broad range of IL1-regulated cytokines, which was attenuated by inhibition of IL1 receptor (IL1R). Our findings suggest that JAG1 and JAG2 have distinct biological roles including a previously undiscovered role for JAG2 in regulating the expression of cytokines that can promote antitumor immunity.
Producing object-based special effects by fusing multiple differently focused images (2000)

We propose a novel approach for producing special visual effects by fusing multiple differently focused images. This method differs from conventional image fusion techniques because it enables us to arbitrarily generate object-based visual effects such as blurring, enhancement, and shifting. Notably, the method does not need any segmentation. Using a linear imaging model, it directly generates the desired image from multiple differently focused images.
Ambient Ion Soft Landing (2011)

Ambient ion soft landing, a process in which polyatomic ions are deposited from air onto a surface at a specified location under atmospheric pressure, is described. Ions generated by electrospray ionization are passed pneumatically through a heated metal drying tube, their ion polarity is selected using ion deflectors, and the dry selected ions are soft-landed onto a selected surface. Unlike the corresponding vacuum soft-landing experiment, where ions are mass-selected and soft-landed within a mass spectrometer, here the ions to be deposited are selected through the choice of a compound that gives predominantly one ionic species upon ambient ionization; no mass analysis is performed during the soft landing experiment. The desired dry ions, after electrical separation from neutrals and counterions, are deposited on a surface. Characterization of the landed material was achieved by dissolution and analysis using mass spectrometry or spectrofluorimetry. The treated surface was also characterized using fluorescence microscopy, which allowed surfaces patterned with fluorescent compounds to be imaged. The pure dry ions were used as reagents in heterogeneous ion/surface reactions including the reaction of pyrylium cations with d-lysine to form the N-substituted pyridinium cation. The charged microdroplets associated with incompletely dried ions could be selected for soft landing or surface reaction by choice of the temperature of a drying tube inserted between the ion source and the electrical ion deflectors.
Receptors for fibrinogen and aggregated beta 2-microglobulin detected in strains of group B streptococci (1981)

Binding of radiolabeled human fibrinogen and aggregated beta-microglobulin was measured in 60 strains of beta-hemolytic group B streptococci. Positive fibrinogen binding was detected in seven of the strains. Six of the group B strains showed an uptake of aggregated beta 2-microglobulin. Four individual strains carried both receptors, indicating a positive correlation between their occurrence. Inhibition studies showed that fibrinogen competed sterically with beta 2-microglobulin binding. Receptors for both proteins were trypsin sensitive. The presence of receptors did not correlate with the serological type of the 49 group B strains tested. However, all seven type II strains were negative. No uptake of fibrinogen was noted in any of 40 group D strains tested. Binding structures for fibrinogen and aggregated beta 2-microglobulin detected in group B streptococci were similar to receptors for the same proteins in group A, C, and G streptococci in terms of mutual correlation and steric interference of binding. The occasional occurrence of these receptors also in group B strains might reflect a common origin of some types of surface proteins in gram-positive cocci.
Clinical utility of echocontrast agents in neurosonology (2004)

Echocontrast agents give additional information on the patient's vascular situation that is often crucial to planning further diagnostic and therapeutic steps. The use of second-generation gas-filled microbubbles, such as SonoVue in transcranial neurosonology, may help to avoid unnecessary, expensive and potentially harmful additional investigations such as intra-arterial DSA. Future applications include the visualization of brain tissue perfusion.
Nearest neighbor queries (1995)

A frequently encountered type of query in Geographic Information Systems is to find the k nearest neighbor objects to a given point in space. Processing such queries requires substantially different search algorithms than those for location or range queries. In this paper we present an efficient branch-and-bound R-tree traversal algorithm to find the nearest neighbor object to a point, and then generalize it to finding the k nearest neighbors. We also discuss metrics for an optimistic and a pessimistic search ordering strategy as well as for pruning. Finally, we present the results of several experiments obtained using the implementation of our algorithm and examine the behavior of the metrics and the scalability of the algorithm.
Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function (2014)

Nonalcoholic steatohepatitis (NASH) is increasing in prevalence, yet its consequences for liver function are unknown. We studied ureagenesis, an essential metabolic liver function of importance for whole body nitrogen homeostasis, in a rodent model of diet-induced NASH. Rats were fed a high-fat, high-cholesterol diet for 4 and 16 wk, resulting in early and advanced experimental NASH, respectively. We examined the urea cycle enzyme mRNAs in liver tissue, the hepatocyte urea cycle enzyme proteins, and the in vivo capacity of urea-nitrogen synthesis (CUNS). Early NASH decreased all of the urea cycle mRNAs to an average of 60% and the ornithine transcarbamylase protein to 10%, whereas the CUNS remained unchanged. Advanced NASH further decreased the carbamoyl phosphate synthetase protein to 63% and, in addition, decreased the CUNS by 20% [from 5.65 ± 0.23 to 4.58 ± 0.30 μmol × (min × 100 g)(-1); P = 0.01]. Early NASH compromised the genes and enzyme proteins involved in ureagenesis, whereas advanced NASH resulted in a functional reduction in the capacity for ureagenesis. The pattern of urea cycle perturbations suggests a prevailing mitochondrial impairment by NASH. The decrease in CUNS has consequences for the ability of the body to adjust to changes in the requirements for nitrogen homeostasis e.g., at stressful events. NASH, thus, in terms of metabolic consequences, is not an innocuous lesion, and the manifestations of the damage seem to be a continuum with increasing disease severity.
<title>Improving transducer performance using multiple active layers</title> (1992)

The performance of a transducer possessing several piezoelectric layers is discussed. Techniques are presented for determining excitation functions so that a pre-defined transmission characteristic is obtained in an optimal manner. The performance of a multiple layer transducer in the reception mode is considered in detail. It is evident that a high degree of transmission and reception efficiency is attainable continuously from below the fundamental thickness mode resonance to above its third harmonic. This contrasts with conventional designs which possess a null at the second harmonic. Issues regarding the stability of the technique are addressed.
Use of kernel deep convex networks and end-to-end learning for spoken language understanding (2012)

We present our recent and ongoing work on applying deep learning techniques to spoken language understanding (SLU) problems. The previously developed deep convex network (DCN) is extended to its kernel version (K-DCN) where the number of hidden units in each DCN layer approaches infinity using the kernel trick. We report experimental results demonstrating dramatic error reduction achieved by the K-DCN over both the Boosting-based baseline and the DCN on a domain classification task of SLU, especially when a highly correlated set of features extracted from search query click logs are used. Not only can DCN and K-DCN be used as a domain or intent classifier for SLU, they can also be used as local, discriminative feature extractors for the slot filling task of SLU. The interface of K-DCN to slot filling systems via the softmax function is presented. Finally, we outline an end-to-end learning strategy for training the softmax parameters (and potentially all DCN and K-DCN parameters) where the learning objective can take any performance measure (e.g. the F-measure) for the full SLU system.
CXCL10 reduces melanoma proliferation and invasiveness in vitro and in vivo (2010)

The quantitative increase in CXCL10 production, together with its ability to limit melanoma progression, shows the potential benefit of this chemokine to control melanoma progression or metastasis.
Toward Gene Therapy for Hemophilia A: Long-Term Persistence of Factor VIII-Secreting Fibroblasts after Transplantation into Immunodeficient Mice (1993)

Hemophilia A is caused by the lack of functional blood-clotting factor VIII. We have used retrovirus-mediated gene transfer to generate various cell lines, rodent as well as human, that secrete the human factor VIII protein. To study whether transplantation of genetically modified fibroblasts is a feasible approach for gene therapy of hemophilia A, we implanted the factor VIII-secreting cells into immune-deficient mice. Implantation of factor VIII-secreting primary human skin fibroblasts resulted in long-term persistence of the transplanted cells; cells recovered from the implants up to 2 months post-implantation still had the capacity to secrete factor VIII when regrown in tissue culture. However, we were unable to detect any human factor VIII in plasma samples of the recipient mice. The absence of human factor VIII in the recipients' plasma is shown to be due neither to (epigenetic) inactivation of the retroviral vector in vivo, nor to inability of the stationary cells to secrete factor VIII protein. However, we did note a rapid clearing of the human factor VIII: CAg from plasma upon intravenous injection of plasma-derived human factor VIII in mice (t1/2 < 60 min vs. 10 hr in humans). This phenomenon can fully explain the apparent absence of human factor VIII in the recipients' plasma.
BIDIRECTIONAL INCREMENTAL PARSING FOR AUTOMATIC PATHWAY IDENTIFICATION WITH COMBINATORY CATEGORIAL GRAMMAR (2000)

As the importance of automatically extracting and analyzing various natural language assertions about protein-protein interactions in biomedical publications is recognized, many uses of natural language processing techniques are proposed in the literature. However, most proposals to date make rather simplifying assumptions about the syntactic aspects of natural language due to various reasons including efficiency. In this paper, we describe an implemented system that utilizes combinatory categorical grammar known to be competent in modeling natural language, with a controlled mechanism for the parser to operate bidirectionally and incrementally. We discuss the performance of the system on a large set of abstracts in Medline with quite encouraging results.
BMP4 regulation of human megakaryocytic differentiation is involved in thrombopoietin signaling (2008)

Activin A, BMP2, and BMP4, 3 members of the transforming growth factor-beta family, are involved in the regulation of hematopoiesis. Here, we explored the role of these molecules in human megakaryopoiesis using an in vitro serum-free assay. Our results highlight for the first time that, in the absence of thrombopoietin, BMP4 is able to induce CD34(+) progenitor differentiation into megakaryocytes through all stages. Although we have previously shown that activin A and BMP2 are involved in erythropoietic commitment, these molecules have no effect on human megakaryopoietic engagement and differentiation. Using signaling pathway-specific inhibitors, we show that BMP4, like thrombopoietin, exerts its effects on human megakaryopoiesis through the JAK/STAT and mTor pathways. Inhibition of the BMP signaling pathway with blocking antibodies, natural soluble inhibitors (FLRG or follistatin), or soluble BMP receptors reveals that thrombopoietin uses the BMP4 pathway to induce megakaryopoiesis, whereas the inverse is not occurring. Finally, we show that thrombopoietin up-regulates the BMP4 autocrine loop in megakaryocytic progenitors by inducing their production of BMP4 and up-regulating BMP receptor expression. In summary, this work indicates that BMP4 plays an important role in the control of human megakaryopoiesis.
Pharmacological strategies in relieving neuropathic pain (2004)

The pharmacological treatment of neuropathic pain relies, to a large extent, on drugs belonging to a small number of defined classes. Opioids, tricyclic antidepressants, antiepileptic drugs and membrane stabilisers form the current basis of treatment. Varying levels of evidence support the use of individual members of these classes and overall show no indication that one class of drug, or individual drug has universal effectiveness. More refined knowledge of the modes of action of these agents used to treat neuropathic pain should lead to a more logical approach to the management of this difficult series of conditions. A number of drugs currently licensed for a different indication have recently had an analgesic effect in neuropathic pain attributed to them. In addition, a number of novel compounds are undergoing investigation and provide hope of dicovering more efficacious treatment options in the future.
Molecular analysis of the poly(3-hydroxyalkanoate) synthase gene from a methylotrophic bacterium, Paracoccus denitrificans (1996)

A 3.6-kb EcoRI-SalI fragment of Paracoccus denitrificans DNA hybridized with a DNA probe carrying the poly(3-hydroxyalkanoate) (PHA) synthase gene (phaC) of Alcaligenes eutrophus. Nucleotide sequence analysis of this region showed the presence of a 1,872-bp open reading frame (ORF), which corresponded to a polypeptide with a molecular weight of 69,537. Upstream of the ORF, a promoter-like sequence was found. Escherichia coli carrying the fusion gene between lacZ and the ORF accumulated a level of poly(3-hydroxybutyrate) that was as much as 20 wt% of the cell dry weight in the presence of beta-ketothiolase and acetoacetylcoenzyme A reductase genes of A. eutrophus. The ORF was designated phaCPd. A plasmid vector carrying the phaCPd'-'lacZ fusion gene downstream of the promoter-like sequence expressed beta-galactosidase activity in P. denitrificans. When a multicopy and broad-host-range vector carrying the ORF along with the promoter-like sequence was introduced into P. denitrificans, the PHA content in the cells increased by twofold compared with cells carrying only a vector sequence.
Choroidal effusion occurrence at the initial onset of phacoemulsification cataract surgery (2015)

An 80-year-old mildly hypertensive patient was scheduled for topical clear corneal phacoemulsification cataract surgery in his right eye. The patient had moderately dense bilateral cataracts and a long-standing exotropia. The rest of the ophthalmic examination was normal. During the initial 1.1 mm paracentesis, the patient reported pain, the anterior chamber became shallow, and the iris prolapsed toward the paracentesis. Intraocular lidocaine was instilled, and the iris prolapsed through the paracentesis accompanied by significant anterior chamber shallowing. The eye was firm to palpation. On indirect ophthalmoscopy, a choroidal effusion but no choroidal hemorrhage was identified. The iris was reposited and the paracentesis closed. The elevated intraocular pressure (IOP) was treated, and the choroidal effusion resolved over a few weeks without permanent damage. This report suggests that even minimal surgical manipulation that lowers the IOP can trigger a choroidal effusion in certain patients. Financial Disclosure The author has no financial or proprietary interest in any material or method mentioned.