gebhart/patrepeval huggingface dataset:
The age of anxiety: role of animal models of anxiolytic action in drug discovery (2011)

Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.
Genome-wide analysis of STAT target genes: Elucidating the mechanism of STAT-mediated oncogenesis (2004)

Inappropriate activation of transcription factors is a common event in cancer. These transcription factors contribute to a malignant phenotype by regulating genes involved in cellular proliferation, survival, differentiation, angiogenesis, and invasion. An important goal remains identifying the targets of oncogenic transcription factors that execute these changes. STAT proteins are among the best-studied of these transcription factors, and are involved in oncogenesis both in vivo and in vitro. They thus represent an ideal model for understanding how transcription factors cause cancer through coordinated changes in gene expression. Recent studies have employed microarray-based expression analysis to comprehensively identify STAT target genes. Analysis of these targets can provide insight into mechanisms of neoplastic transformation, and may shed light on new strategies for targeted therapy.
Lu-ECAM-1-mediated adhesion of melanoma cells to endothelium under conditions of flow (1996)

Lu-ECAM-1 is a lung-derived, venular endothelial cell adhesion molecule. It promotes the selective adhesion of lung-metastatic B16-F10 melanoma cells to endothelium under static conditions and mediates colonization of the lungs by the same tumor cells. To test whether Lu-ECAM-1 by itself is sufficient to cause vascular arrest of B16-F10 cells, we measured here under conditions of flow tumor cell adhesion to endothelia that express different amounts of Lu-ECAM-1 on their surfaces. At physiological shear stresses, adhesion of B16-F10 melanoma cells to endothelia correlates positively with the amount of Lu-ECAM-1 expression on the endothelial cell surface and inversely with the level of the applied shear stress. Tumor cell trajectories are biphasic; i.e., B16-F10 melanoma cells initially move along the endothelial surface with a velocity similar to the theoretical velocity, then arrest within a fraction of a second. Arrest is permanent for most B16-F10 melanoma cells at all shear stresses tested. Tumor cells never engaged in a rolling motion prior to arrest. Masking of the Lu-ECAM-1 ligand on the surface of B16-F10 melanoma cells with soluble Lu-ECAM-1 impedes arrest of tumor cells on the surface of the test endothelium. Purified Lu-ECAM-1 also mediates B16-F10 arrest, but arrest is mostly transient at shear stresses of 0.59 dynes/cm2 and higher, implying adhesion by single receptor/ligand bonds. Our data suggest that Lu-ECAM-1 plays a critical role in the recognition and initial arrest of murine melanoma cells in lung venules.
Fast and Reliable Active Appearance Model Search for 3-D Face Tracking (2004)

This paper addresses the three-dimensional (3-D) tracking of pose and animation of the human face in monocular image sequences using active appearance models. The major problem of the classical appearance-based adaptation is the high computational time resulting from the inclusion of a synthesis step in the iterative optimization. Whenever the dimension of the face space is large, a real-time performance cannot be achieved. In this paper, we aim at designing a fast and stable active appearance model search for 3-D face tracking. The main contribution is a search algorithm whose CPU-time is not dependent on the dimension of the face space. Using this algorithm, we show that both the CPU-time and the likelihood of a nonaccurate tracking are reduced. Experiments evaluating the effectiveness of the proposed algorithm are reported, as well as method comparison and tracking synthetic and real image sequences.
COX-2 inhibitors vs. NSAIDs in gastrointestinal damage and prevention (2001)

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit production of protective gastric mucosal prostaglandins and also have a direct topical irritant effect. In some patients this results in dyspepsia and development of gastroduodenal erosions and ulceration. The risk of ulcer complications, such as bleeding, perforation and death is increased approximately 4-fold in NSAID users. Patients at high risk of ulcer complications include the elderly, those taking anticoagulants, steroids and aspirin, those with a previous history of peptic ulceration and patients with concomitant serious medical problems. The interaction of NSAIDs with Helicobacter pylori (the major cause of peptic ulceration in non-NSAID users) is controversial and some studies suggest that H. pylori infection may even protect against NSAID-induced ulceration. Selective inhibitors of the inducible cyclooxygenase-2 (COX-2) enzyme spare COX-1 in the gastric mucosa and, hence, do not inhibit production of mucosal prostaglandins. COX-2-selective inhibitors are associated with a significant reduction in gastroduodenal damage compared with traditional NSAIDs. Proton pump inhibitors (PPI) are probably the best agents for healing and prevention of NSAID-induced ulcers. Preliminary studies suggest that COX-2 selective inhibitors, like traditional NSAIDs, may prevent lower gastrointestinal cancer. Further studies are needed but they may be useful in individuals at high risk of certain types of lower gastrointestinal malignancy with increased gastrointestinal tolerability and safety.
Effects of 810 nm laser irradiation on in vitro growth of bacteria: Comparison of continuous wave and frequency modulated light (2002)

The findings of this study point to the need for wound cultures prior to laser irradiation of infected wounds. Similar investigations using other common therapeutic wavelengths are recommended.
Cypress pollen allergy. Identification of allergens and crossreactivity between divergent species (1994)

Studies employing sera from 34 subjects allergic to white cypress pine (Callitris glaucophylla) pollen identified 18 IgE antibody-binding components in the pollen of this species, five of which (MWs approximately 94, 68, 64, 43 and 34 kDa) were recognized by all of the sera. Protein blotting and quantitative inhibition studies revealed clear cross-reactivity between C. glaucophylla and Cupressus sempervirens pollen proteins and striking similarities in the IgE recognition band patterns of the two pollens. Inhibition experiments with other pollen extracts revealed that sera from C. glaucophylla pollen-allergic subjects can be divided into two groups--those inhibited only by extracts from the two Cupressaceae pollens and those inhibited both by these pollen proteins and by pollen extracts from other species. Most of the crossreactions in the latter group cannot be explained on the basis of taxonomic relationships or separate sensitizations. As with previous studies on birch and olive pollens, we conclude that pollen allergenic crossreactivity is much more wide-ranging than generally believed.
Contrast agents and spectroscopic probes in NMR. (1984)

The demand for higher diagnostic specificity has led to the increased use of "foreign" agents to increase tissue contrast and/or spectroscopic sensitivity in NMR studies. The primary agents used to enhance tissue contrast in NMR imaging are paramagnetic. They cause a decrease in the proton T1 of H2O leading to enhanced signal intensity. This effect depends on the large gyromagnetic ratio of the electron, the number of unpaired electrons, the concentration of paramagnetic ions, the number of coordinated water molecules, and the rate of exchange of water. Spectroscopic enhancement has relied primarily on attempt at isotopic enrichment (usually C-13), which causes a direct increase in signal.
Glutamate 139 of the Large .alpha.-Subunit Is the Catalytic Base in the Dehydration of Both D- and L-3-Hydroxyacyl-Coenzyme A But Not in the Isomerization of .DELTA.3,.DELTA.2-Enoyl-Coenzyme A Catalyzed by the Multienzyme Complex of Fatty Acid Oxidation from Escherichia coli (1995)

Multienzyme complexes of fatty acid oxidation from Escherichia coli with either an alpha/Glu139-->Gln or an alpha/Arg134-->Gln mutation in the large alpha-subunit have been overproduced and characterized. The catalytic properties of the five different component enzymes of the alpha/Arg134-->Gln mutant complex showed no significant changes as compared with those of the wild type complex. In contrast, the 3-hydroxyacyl-coenzyme A (CoA) epimerase activity of the alpha/Glu139-->Gln mutant complex was not detected, and this mutant complex has lost almost all of the enoyl-CoA hydratase activity due to a greater than 3000-fold decrease in the kcat of the enoyl-CoA hydratase without a significant change in the Km value. The catalytic properties of 3-ketoacyl-CoA thiolase and L-3-hydroxyacyl-CoA dehydrogenase were virtually unaffected by the mutation. Together, these observations lead to the conclusion that the gamma-carboxylic group of Glu139 functions as a catalytic base in the dehydration of both D- and L-3-hydroxyacyl-CoA. These findings also support a dehydration/hydration mechanism for 3-hydroxyacyl-CoA epimerase but do not agree with an epimerase activity independent of enoyl-CoA hydratase as proposed for the glyoxysomal tetrafunctional protein [Preisig-Müller, R., Gühnemann-Schäfer, K., & Kindl, H. (1994) J. Biol. Chem. 269, 20475-20481]. Since this mutation caused the kcat of delta 3-cis-delta 2-trans-enoyl-CoA isomerase to decrease by only 60%, even though the Km value was significantly increased, it seems that Glu139 of the E. coli multifunctional protein does not function as a catalytic residue in the isomerization reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Critical role of the A2 amino acid residue in the biological activity of insulin: [2-glycine-A]- and [2-alanine-A]insulins (1984)

We report the synthesis of [2-glycine-A]insulin ([ Gly2 -A]insulin) and [2-alanine-A]insulin ([ Ala2-A]insulin) in which the indicated amino acid has been substituted for isoleucine found in this position in the natural hormone. The circular dichroic (CD) spectra of the analogues were obtained, and their properties were examined in several biological assays. CD studies suggested that the analogues remain monomeric at concentrations at which insulin is partly or mostly dimeric. Both analogues are extremely weak full agonists. [ Gly2 -A]-insulin displays 0.05% of the potency of bovine insulin, whereas [Ala2-A]insulin assays at 0.4% of the activity of the natural hormone. We conclude that the presence of the side chain of isoleucine at position A2 is a critical requirement for high biological activity in insulin. The data, together with previous observations, are discussed in connection with an interaction between the side chain of isoleucine-A2 and the phenolic ring system of tyrosine-A19, which are in van der Waals contact in crystalline insulin. This interaction may be required to permit the molecule to assume a conformation consistent with dimerization and with binding to the insulin receptor.
Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density (2004)

These data demonstrate that elevated 1,25(OH)(2)D is more common in CD than previously appreciated and is independently associated with low bone mineral density. The source of the active vitamin D may be the inflamed intestine. Treatment of the underlying inflammation may improve metabolic bone disease in this subgroup of patients.
Nerves in a human body exposed to low-frequency electromagnetic fields (1999)

Following a summarizing introduction in which the background research is reviewed and referenced, a detailed description is given of the properties of the elongated cell that constitutes a nerve axon. The functioning of the cell membrane is reviewed with reference to the transmission of a frequency-modulated signal. The need for successive regeneration by means of action potentials is described. Propagation within both myelinated and unmyelinated membranes is discussed. Currents and electric fields induced in the organs of the human body by external electric and magnetic fields are introduced and their determination reviewed. The interaction between these currents and electric fields and those involved in the propagation of a signal along a nerve axon is analyzed. It is shown that incident 60-Hz electric fields near high-voltage transmission lines do not induce large enough currents and fields in a nerve axon in the leg to disrupt a propagating signal. Scaling with respect to frequency and size is discussed. Surface sensations due to exposure to electric fields in the 5-15-kV/m range are analyzed. It is concluded that exposure to the electromagnetic field of a 60-Hz high-voltage transmission line or a 10-30-kHz high-power transmitting antenna should have no observable effect on the normal functioning of nerves.
Effect of lithium on stem cell and stromal cell proliferation in vitro. (1986)

Lithium is recognized as a potent stimulator of hematopoiesis both in vivo and in vitro. Previous work has suggested that this stimulation is mediated as an indirect, humoral effect by the action of lithium upon the stromal cell population. In the present study, the effects of lithium on the stromal population were investigated using a long-term liquid marrow culture model. These findings indicate that exposure of in vitro cultures to lithium results in an increase in the total cellularity and in the number of various hematopoietic progenitor cells residing within the stromal layer. A distinct morphologically recognizable cell has not been identified as the target cell responsible for the indirect stimulation of hematopoiesis by lithium. However, two candidate radioresistant stromal cells believed to be active in the production of humoral mediators of hematopoiesis did proliferate in response to lithium exposure.
Induction of Particle Polymorphism by Cucumber Necrosis Virus Coat Protein Mutants In Vivo (2007)

The Cucumber necrosis virus (CNV) particle is a T=3 icosahedron consisting of 180 identical coat protein (CP) subunits. Plants infected with wild-type CNV accumulate a high number of T=3 particles, but other particle forms have not been observed. Particle polymorphism in several T=3 icosahedral viruses has been observed in vitro following the removal of an extended N-terminal region of the CP subunit. In the case of CNV, we have recently described the structure of T=1 particles that accumulate in planta during infection by a CNV mutant (R1+2) in which a large portion of the N-terminal RNA binding domain (R-domain) has been deleted. In this report we further describe properties of this mutant and other CP mutants that produce polymorphic particles. The T=1 particles produced by R1+2 mutants were found to encapsidate a 1.9-kb RNA species as well as smaller RNA species that are similar to previously described CNV defective interfering RNAs. Other R-domain mutants were found to encapsidate a range of specifically sized less-than-full-length CNV RNAs. Mutation of a conserved proline residue in the arm domain near its junction with the shell domain also influenced T=1 particle formation. The proportion of polymorphic particles increased when the mutation was incorporated into R-domain deletion mutants. Our results suggest that both the R-domain and the arm play important roles in the formation of T=3 particles. In addition, the encapsidation of specific CNV RNA species by individual mutants indicates that the R-domain plays a role in the nature of CNV RNA encapsidated in particles.
Omega-3 fatty acids and blood pressure. (2010)

There is substantial evidence that omega-3 fatty acids reduce blood pressure, with a greater effect in hypertensive patients and those with high-normal blood pressure. The dose of omega-3 fatty acids required to achieve a blood pressure reduction is likely to be at least 3-4 g/day. However, the magnitude of the blood pressure change can be increased by salt restriction or when omega-3 fatty acids are incorporated into a weight reducing program. It is also highly plausible that increased omega-3 fatty acid consumption as part of a dietary change including increased consumption of fruits and vegetables, and moderation of salt intake, will confer significant cardiovascular benefit.
Detection of Ehrlichia chaffeensis in human tissue by using a species-specific monoclonal antibody (1993)

A mouse monoclonal antibody (MAb 1A9) was produced and used in detection of Ehrlichia chaffeensis in human tissues including kidney, liver, and lung by using an indirect immunohistologic stain. MAb 1A9 was specific to E. chaffeensis and did not react with other bacteria, including Ehrlichia canis, which is the organism most closely related to E. chaffeensis. It reacted with an epitope present in two surface proteins of E. chaffeensis with molecular masses of 29 and 27 kDa. E. chaffeensis was easily detected in human tissue by immunohistology with MAb 1A9. This study demonstrates that our MAb can provide a specific and simple method for detection of E. chaffeensis in clinical specimens for establishing an etiologic diagnosis of human ehrlichiosis; it may also provide a tool for the investigation of immunopathologic characteristics in infected patients.
Parallel database systems (1992)

Abstract: Parallel database machine architectures have evolved from the use of exotic hardware to a software parallel dataflow architecture based on conventional shared-nothing hardware. These new designs provide impressive speedup and scaleup when processing relational database queries. This paper reviews the techniques used by such systems, and surveys current commercial and research systems. 1.
Conjugates of Peptides and Proteins to Polyethylene Glycols (2004)

This chapter provides a critical overview of the technology presently available in the field of protein PEGylation. The chemistry of the polymer and of its reactive derivatives is discussed and presented together with several protocols used to obtain PEG-protein conjugates. The coupling protocols are critically discussed on the basis of the properties of the protein to be modified and those desired for the final product. Methods for product purification and characterization are also provided. The overall information provided will guide the reader toward all of the critical steps involved in the preparation of PEG-protein adducts.
Synthesis and structure-activity studies in a series of 7.alpha.-halogeno corticosteroids (1980)

The preparation and topical antiinflammatory potencies of a series of 7 alpha-halogeno-16-substituted-prednisolone derivatives are described. The 7 alpha-chloro, 7 alpha-bromo, and 7 alpha-iodo corticosteroids were obtained by addition of hydrogen halide to the 6,7-dehydro compounds. The extent of addition of HCl varied with substitution at C-11, while no addition of HF was observed at all. The 7 alpha-fluoro corticosteroids were prepared by reaction of the appropriate 7 beta-hydroxy compounds with N,N-diethyl(2-chloro-1,1,2-trifluoroethyl)amine. The 7 beta-hydroxy steroids were obtained, in turn, from the 6,7-dehydro compounds via the 6 beta,7 beta-dihydroxy derivatives. Antiinflammatory potencies were measured in mice by the Tonelli croton oil ear assay. The greatest effect of a 7 alpha-halogen was observed in the 16 alpha-methylprednisolone series, where 7 alpha-chloro and 7 alpha-bromo substitution increased potency 2.5- to 3.5-fold. Compounds 4b and 5b were equipotent to betamethasone dipropionate. 7 alpha-Halogen substitution in other series produced more variable effects and sometimes led to a reduction of antiinflammatory potency.
Insight into the dry etching of fence-free patterned platinum structures (1997)

An investigation was undertaken to characterize the time progression of the Pt etch process during the dry etching (DE) of fence-free patterned structures. The goal of this study was to clarify the mechanism of fence-free Pt etching. In particular an explanation was sought that could account for the origin of the extremely shallow sidewall angles typically reported in the literature for fence-free Pt etching. The experiment consisted of coprocessing two oxidized Si wafers possessing identical 250 nm thick Pt film layers, but different photoresist (PR) mask thicknesses. Etching was suspended at 20%, 40%, 60%, and 80% of the full etch process in order to cleave off small pieces of wafer for analysis by scanning electron microscopy (SEM). Using Cl2-based DE conditions known to produce fence-free etching for 250 nm thick film layers, we found that a severe fence actually coats the PR mask during the first 20% of the etch process! As the etch continues the fence structure evolves, achieving a maximum height and width followed by progressive recession until disappearing completely prior to process endpoint. SEM micrographs clearly reveal how the existence of these transient fence structures account for the formation of shallow Pt sidewalls. The data also shows that the final profile of an etched Pt structure possesses a functional dependence on the initial thickness and slope of the PR mask as well as on the initial thickness of the Pt layer. Finally, we believe that the observed behavior of the transient fence provides the strongest evidence to date supporting the existence of a chemically assisted physical sputtering component associated with the DE of Pt films in halogen-based plasmas.
Automatic text decomposition using text segments and text themes (1996)

With the widespread use of full-text information retrieval, passage-retrieval techniques are becoming increasingly popular.
PREDICTIVE CODING OF SPEECH USING ANALYSIS-BY-SYNTHESIS TECHNIQUES (2005)

This paper presents an overview of analysis-by-synthesis techniques used for low bit rate coding of speech signals. Analysis-by-synthesis procedures use linear predictors to remove the redundancies in the speech signal. The remaining difference signal is not quantized directly, but is replaced by an excitation signa1 that can be represented with a low number of bits. The selection of this signal is typically based on an exhaustive search procedure, in which for each prototype excitation the corresponding speech signal is constructed. The average mean-squared error between the original and the reconstructed signal is used as a criterion to determine the best choice of Lhe excitation signal. In this paper, different excitation signals are discussed, as well as procedures for determining the various coder parametsrs. In addition, the paper discusses some recently proposed speech coding standards, which are based on analysis-by-synthesis techniques.