gebhart/patrepeval huggingface dataset:
Pharmacokinetics of venlafaxine andO-desmethylvenlafaxine in laboratory animals (1994)

1. The pharmacokinetics of venlafaxine have been evaluated in mouse, rat, dog and rhesus monkey after i.v. and/or i.g. doses of venlafaxine from 2 to 120 mg/kg either as single or repeated doses. 2. In rat, dog and monkey, venlafaxine is a high clearance compound with a large volume of distribution after i.v. administration. 3. Absolute bioavailability was low in rat and rhesus monkey (12.6 and 6.5%, respectively) and moderate in dog (59.8%). Other species differences were seen, including an elimination half-life of venlafaxine that was longer in dog and rhesus monkey (2-4 h) than in rodent (around 1 h). 4. In mouse, rat and dog, exposure to venlafaxine increased more than proportionally with dose, suggesting saturation of elimination. Exposure of venlafaxine decreased with repeated dosing in mouse and rat, but was unchanged in dog. 5. Exposure of animals to the bioactive metabolite, O-desmethylvenlafaxine (ODV), was less than that of venlafaxine itself. ODV was not detected in dog and not measurable in rhesus monkey receiving venlafaxine.
Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6 (2008)

Polo kinases are known key regulators of cell divisions. Here we report a novel, non-cell division function for polo kinases in embryonic polarity of newly fertilized Caenorhabditis elegans embryos. We show that polo kinases, via their polo box domains, bind to and regulate the activity of two key polarity proteins, MEX-5 and MEX-6. These polo kinases are asymmetrically localized along the anteroposterior axis of newly fertilized C. elegans embryos in a pattern identical to that of MEX-5 and MEX-6. This asymmetric localization of polo kinases depends on MEX-5 and MEX-6, as well as genes regulating MEX-5 and MEX-6 asymmetry. We identify an amino acid of MEX-5, T(186), essential for polo binding and show that T(186) is important for MEX-5 function in vivo. We also show that MBK-2, a developmentally regulated DYRK2 kinase activated at meiosis II, primes T(186) for subsequent polo kinase-dependent phosphorylation. Prior phosphorylation of MEX-5 at T(186) greatly enhances phosphorylation of MEX-5 by polo kinases in vitro. Our results provide a mechanism by which MEX-5 and MEX-6 function is temporally regulated during the crucial oocyte-to-embryo transition.
[Hepatoprotective effect of the sea buckthorn-and-pinks oil]. (2000)

Our objective in this study was to reveal hepatoprotective properties of the sea-buckthorn and sea-buckthorn-pink oils in the experiment in shinshilla rats exposed to tetrachloromethane. To assess the progression of hepatitis and recovery processes in hepatic cells we used the organ-specific enzyme sorbitoldegydrogenase (SDG). The results obtained showed that the sea-buckthorn and sea-buckthorn-pink oils promoted normalization of SDG level 5 and 8 days respectively earlier than in the control group, which fact is indicative of their apparent hepatoprotective properties.
Complement activation pathways in murine immune complex-induced arthritis and in C3a and C5a generationin vitro (2009)

The alternative pathway (AP) of complement alone is capable of mediating immune complex-induced arthritis in the collagen antibody-induced arthritis (CAIA) model in mice. Whether the classical pathway (CP) or lectin pathway (LP) alone can mediate CAIA is not known. Using mice genetically deficient in different complement components, our results reported herein establish that the CP and LP alone are each incapable of mediating CAIA. A lower level or absence of C3 and/or C5 activation by the CP may be possible explanations for the importance of the AP in CAIA and in many murine models of disease. In addition, other investigators have reported that CP C5 convertase activity is absent in mouse sera. To address these questions, we employed an in vitro system of adherent immunoglobulin (Ig)G-induced complement activation using plates coated with murine anti-collagen monoclonal antibody (mAb). These experiments used complement-deficient mouse sera and wild-type mouse or normal human sera under conditions inactivating either the CP (Ca(++) deficiency) or the AP (mAb inhibitory to factor B). Robust generation of both C3a and C5a by either the AP or CP alone were observed with both mouse and human sera, although there were some small differences between the species of sera. We conclude that neither the CP nor LP alone is capable of mediating CAIA in vivo and that mouse sera exhibits a high level of IgG-induced C5a generation in vitro through either the CP or AP.
Functional dyspepsia and irritable bowel syndrome: is there a common pathophysiological basis? (1997)

Small intestinal mechanosensitive pathways are disturbed in patients with functional dyspepsia and IBS. Differences in the pattern and localization of symptoms probably do not reflect differences in small intestinal sensory thresholds. Functional dyspepsia and IBS cannot be distinguished on the basis of altered small intestinal sensory thresholds.
Gauss-Newton and full Newton methods in frequency-space seismic waveform inversion (1998)

By specifying a discrete matrix formulation for the frequency–space modelling problem for linear partial differential equations (‘FDM’ methods), it is possible to derive a matrix formalism for standard iterative non-linear inverse methods, such as the gradient (steepest descent) method, the Gauss–Newton method and the full Newton method. We obtain expressions for each of these methods directly from the discrete FDM method, and we refer to this approach as frequency-domain inversion (FDI). The FDI methods are based on simple notions of matrix algebra, but are nevertheless very general. The FDI methods only require that the original partial differential equations can be expressed as a discrete boundary-value problem (that is as a matrix problem). Simple algebraic manipulation of the FDI expressions allows us to compute the gradient of the misfit function using only three forward modelling steps (one to compute the residuals, one to backpropagate the residuals, and a final computation to compute a step length). This result is exactly analogous to earlier backpropagation methods derived using methods of functional analysis for continuous problems. Following from the simplicity of this result, we give FDI expressions for the approximate Hessian matrix used in the Gauss–Newton method, and the full Hessian matrix used in the full Newton method. In a new development, we show that the additional term in the exact Hessian, ignored in the Gauss–Newton method, can be efficiently computed using a backpropagation approach similar to that used to compute the gradient vector. The additional term in the Hessian predicts the degradation of linearized inversions due to the presence of first-order multiples (such as free-surface multiples in seismic data). Another interpretation is that this term predicts changes in the gradient vector due to second-order non-linear effects. In a numerical test, the Gauss–Newton and full Newton methods prove effective in helping to solve the difficult non-linear problem of extracting a smooth background velocity model from surface seismic-reflection data.
Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1 (1986)

We report the complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1, as 6633 base pairs of composition 79.5% G+C. This contains immediate early gene 3, encoding the IE175 protein, an important transcriptional activator of later virus genes. The IE175 coding region was identified as a 3894 base sequence of 81.5% G+C DNA. The base composition of this gene is thus the most extreme yet determined, and the IE175 predicted amino acid composition is correspondingly biased, most notably with an alanine content of 20.9%. Functionally important regions of the IE175 polypeptide were tentatively identified by comparison with the sequence of the homologous protein from varicella-zoster virus and from locations of ts mutations, and were correlated with properties of the amino acid sequence. Aspects of the evolution of such an extreme composition DNA sequence were discussed.
Chemoenzymatic Synthesis of Homogeneous Ultralow Molecular Weight Heparins (2011)

Ultralow molecular weight (ULMW) heparins are sulfated glycans that are clinically used to treat thrombotic disorders. ULMW heparins range from 1500 to 3000 daltons, corresponding from 5 to 10 saccharide units. The commercial drug Arixtra (fondaparinux sodium) is a structurally homogeneous ULMW heparin pentasaccharide that is synthesized through a lengthy chemical process. Here, we report 10- and 12-step chemoenzymatic syntheses of two structurally homogeneous ULMW heparins (MW = 1778.5 and 1816.5) in 45 and 37% overall yield, respectively, starting from a simple disaccharide. These ULMW heparins display excellent in vitro anticoagulant activity and comparable pharmacokinetic properties to Arixtra, as demonstrated in a rabbit model. The chemoenzymatic approach is scalable and shows promise for a more efficient route to synthesize this important class of medicinal agent.
Evaluation of a multi-marker immunomagnetic enrichment assay for the quantification of circulating melanoma cells (2012)

Our results demonstrated that a combination of markers should be targeted for optimal isolation of CMCs. In addition, there are significantly more CMCs in metastatic patients compared with non-metastatic patients and therefore quantification of CMCs may prove to be a useful marker of disease progression.
Selective oxidation of cysteine and methionine in normal and senile cataractous lenses. (1980)

The oxidation state of methionine and cysteine in normal and cataractous lenses is reported. In young lenses no oxidation was detected in any protein fraction examined. Only the intrinsic membrane fraction and membrane-related components showed evidence of oxidation in old (60-65 years of age) normal lenses. However, in a similar age group, with the development of cataract, progressive, dramatic changes were observed. With severe cataracts, 60% or more of the methionine in membrane-associated components was found in the methionine sulfoxide form, and methionine sulfone was observed in one case. Most of the cysteine was found oxidized to either the disulfide form or putative cysteic acid. Mixed disulfides with glutathione were observed. Oxidative changes in soluble components as illustrated by alpha-crystallin occurred more gradually. The data clearly support the viewpoint that extensive oxidation of lens proteins occurs with cataract and that it begins at the lens fiber membrane.
Chemical shift imaging with spectrum modeling (2001)

A new chemical shift imaging technique was developed to efficiently obtain separate images for multiple chemical shift peaks from a set of spin-echo acquisitions. Information from localized NMR spectroscopy was used to model the chemical shift spectrum as sharp peaks with known resonance frequencies but unknown amplitudes. Based on this model, a set of spin-echo images with shifted 180 degrees RF pulses were acquired, in which the magnetization vectors of different chemical components were put into different directions. The amplitudes of the chemical shift peaks were obtained by solving nonlinear equations in a region-growing process. Experimental results on an ethanol phantom as well as a subject with silicone breast implants are presented. Magn Reson Med 46:126-130, 2001.
The Adjuvant Action of Cholera Toxin is Associated with an Increased Intestinal Permeability for Luminal Antigens (1991)

This study addresses the question of whether cholera toxin (CT) increases gut permeability for molecules greater than 3000 Da and whether such an effect is associated with an adjuvant function by CT on the gut immune response. We found that CT after oral administration gives rise to strikingly increased gut permeability for Dextran (Mw 3000) concomitantly with a strong enhancing effect on the anti-keyhole limpet hemocyanin (KLH) specific immune response in the lamina propria after oral immunization with KLH plus Dextran and CT. In contrast, the B-subunit of the holotoxin, which lacks the adenylate cyclase/cAMP-activating property of CT, failed to increase gut permeability as well as local anti-KLH immune responses. These results might suggest a causal linkage between the ability of CT to increase gut permeability and its adjuvant property on gut mucosal immune responses. In addition this finding supports the notion that the adenylate cyclase/cAMP system plays a regulatory role in gut permeability and is important in enhancing mucosal immune responses. Based on previous studies and the present data we propose that the mechanism for CT's adjuvant function on mucosal immune responses is by affecting antigen-presenting cells, T and B cells in the gut to give a net enhancing effect on the stimulation of local immunity, and that the CT-induced increase in gut permeability might be part of the adjuvant mechanism by facilitating luminal antigens to access the gut mucosal immune system.
Systematic review: the evidence base for long‐term management of coeliac disease (2008)

Evidence (albeit limited) that adherence to a gluten-free diet and mucosal healing prevent and/or ameliorate complications indicates that a planned long-term strategy for follow-up is essential.
Continuous quantum error correction via quantum feedback control (2002)

We describe a protocol for continuously protecting unknown quantum states from decoherence that incorporates design principles from both quantum error correction and quantum feedback control. Our protocol uses continuous measurements and Hamiltonian operations, which are weaker control tools than are typically assumed for quantum error correction. We develop a cost function appropriate for unknown quantum states and use it to optimize our state-estimate feedback. Using Monte Carlo simulations, we study our protocol for the three-qubit bit-flip code in detail and demonstrate that it can improve the fidelity of quantum states beyond what is achievable using quantum error correction when the time between quantum error-correction cycles is limited.
Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors (2016)

The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors.
Guide to pattern recognition using random-access memories (1979)

About 12 years of work with a specific type of learning pattern-recognition system are reviewed. The principles and characteristics of the scheme, which is based on random-access-memory implementation, are discussed in some detail. Methods of improving performance and cost-optimising pattern recognisers are presented, together with case studies in a variety of fields including the recognition of alphanumerics, chemical data and faults in digital circuit boards.
Anti-immunoglobulin E for the treatment of allergic disease (2001)

IgE plays a central role in allergic disease and participates in the associated inflammatory process. A mainstay of treatment of allergic disease, including asthma, is allergen avoidance and treatment of symptoms. Presently, the most effective treatments for allergic diseases are directed towards a regulation of the inflammatory process with corticosteroids. An exciting new approach is anti-IgE (rhuMAb-E25), which would regulate the allergic process at the level of IgE. The following information will review recent experiences with anti-IgE and discuss the conditions in which this approach may be effective.
Fiber Faraday rotator (1984)

A single-mode fiber Faraday rotator is proposed and fabricated by using a paramagnetic glass with a high Verdet constant. The Faraday rotator is a W-fiber with three layers, namely, core, inner cladding, and outer cladding. To make the fiber FR-5 is used as the starting material. The Verdet constant of the rotator is −0.25 min/Oe·cm at a 0.633-μm wavelength. The rotator can be used in a fiber isolator.
Noncontact modal testing of hard-drive suspensions using ultrasound radiation force (2005)

The head-gimbal assembly suspension is a cantilever-like structure that holds the heads on a hard drive. We will discuss a noncontact method for modal testing, of suspensions in air, that utilizes the radiation force at the difference frequency generated by two intersecting ultrasound beams. The resulting low-frequency excitations were measured using a scanning vibrometer. This excitation technique has been demonstrated for MEMS and other small devices. There are several unique advantages of the ultrasound radiation force relative to mechanical shakers. Since the ultrasound radiation force is noncontact, a specialized test fixture was not needed; the technique was relatively insensitive to distracting resonances of fixtures and support structures. Another advantage is broadband excitation; a 550-kHz confocal ultrasound transducer excited suspension resonance frequencies from under 1 kHz to over 50 kHz. Other advantages include the ability to selectively excite different modes. For example, the amplitude of the suspension’s 2.28-kHz transverse mode was suppressed by an order of magnitude by shifting the modulation phase between the two ultrasound beams by 90. In another test, the amplitude of the 6.01-kHz torsional mode was doubled by moving the ultrasound focus point from near the center to near the edge of the suspension.
A 9-nt segment of a cellular mRNA can function as an internal ribosome entry site (IRES) and when present in linked multiple copies greatly enhances IRES activity (2000)

This study addresses the properties of a newly identified internal ribosome entry site (IRES) contained within the mRNA of the homeodomain protein Gtx. Sequential deletions of the 5' untranslated region (UTR) from either end did not define distinct IRES boundaries; when five nonoverlapping UTR fragments were tested, four had IRES activity. These observations are consistent with other cellular IRES analyses suggesting that some cellular IRESes are composed of segments (IRES modules) that independently and combinatorially contribute to overall IRES activity. We characterize a 9-nt IRES module from the Gtx 5' UTR that is 100% complementary to the 18S rRNA at nucleotides 1132-1124. In previous work, we demonstrated that this mRNA segment could be crosslinked to its complement within intact 40S subunits. Here we show that increasing the number of copies of this IRES module in the intercistronic region of a dicistronic mRNA strongly enhances IRES activity in various cell lines. Ten linked copies increased IRES activity up to 570-fold in Neuro 2a cells. This level of IRES activity is up to 63-fold greater than that obtained by using the well characterized encephalomyocarditis virus IRES when tested in the same assay system. When the number of nucleotides between two of the 9-nt Gtx IRES modules was increased, the synergy between them decreased. In light of these findings, we discuss possible mechanisms of ribosome recruitment by cellular mRNAs, address the proposed role of higher order RNA structures on cellular IRES activity, and suggest parallels between IRES modules and transcriptional enhancer elements.
Negative Feedback Loop of Wnt Signaling through Upregulation of Conductin/Axin2 in Colorectal and Liver Tumors (2002)

Activation of Wnt signaling through β-catenin/TCF complexes is a key event in the development of various tumors, in particular colorectal and liver tumors. Wnt signaling is controlled by the negative regulator conductin/axin2/axil, which induces degradation of β-catenin by functional interaction with the tumor suppressor APC and the serine/threonine kinase GSK3β. Here we show that conductin is upregulated in human tumors that are induced by β-catenin/Wnt signaling, i.e., high levels of conductin protein and mRNA were found in colorectal and liver tumors but not in the corresponding normal tissues. In various other tumor types, conductin levels did not differ between tumor and normal tissue. Upregulation of conductin was also observed in the APC-deficient intestinal tumors of Min mice. Inhibition of Wnt signaling by a dominant-negative mutant of TCF downregulated conductin but not the related protein, axin, in DLD1 colorectal tumor cells. Conversely, activation of Wnt signaling by Wnt-1 or dishevelled increased conductin levels in MDA MB 231 and Neuro2A cells, respectively. In time course experiments, stabilization of β-catenin preceded the upregulation of conductin by Wnt-1. These results demonstrate that conductin is a target of the Wnt signaling pathway. Upregulation of conductin may constitute a negative feedback loop that controls Wnt signaling activity.
An Adaptation of the Transparent-Chamber Technique to the Mouse (1943)

Journal Article An Adaptation of the Transparent-Chamber Technique to the Mouse Get access Glenn H. Algire Glenn H. Algire National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 1, August 1943, Pages 1–11, https://doi.org/10.1093/jnci/4.1.1 Published: 01 August 1943
Review of excipients and pH's for parenteral products used in the United States. (1981)

Excipients used in U.S. parenteral products were categorized according to their/unction. The concentrations used in commercial products were also identified. The range of pH value in various products was tabulated with emphasis on products with extreme pH’s. The uses of excipients in parenteral dosage form were discussed.