gebhart/patrepeval huggingface dataset:
Relationships among human amniotic fluid dipalmitoyl lecithin, postpartum respiratory compliance, and neonatal respiratory distress syndrome. (1983)

The major molecular species of amniotic fluid phosphatidylcholine were determined as diacylglycerol trimethylsilyl ether derivatives by gas-liquid chromatography with use of glass capillary columns. We studied amniotic fluid specimens from 48 pregnancies. As expected, the major disaturated species of amniotic fluid phosphatidylcholine, dipalmitoylphosphatidylcholine, and palmitoylmyristoylphosphatidylcholine increased with gestational age, whereas phosphatidylcholine species with 34, 36, and 38 carbon atoms in the acyl radicals decreased. Although the amniotic fluid samples were obtained shortly before parturition (4.2 +/- 3.7 h, mean +/- SD), the correlation between dipalmitoylphosphatidylcholine concentration in amniotic fluid and gestational age was better than between dipalmitoylphosphatidylcholine concentration and the compliance of the respiratory system of the newborns. In addition, the percentage of amniotic fluid phosphatidylcholine species present as dipalmitoylphosphatidylcholine seemed to be a more reliable predictor of lung maturity than was the absolute dipalmitoylphosphatidylcholine concentration in amniotic fluid.
From Hit to Lead. Combining Two Complementary Methods for Focused Library Design. Application to μ Opiate Ligands (2001)

Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.
CGRP antagonists: hope for a new era in acute migraine treatment. (2009)

Calcitonin gene-related peptide (CGRP) has a widespread distribution throughout the trigeminovascular system and other brain areas involved in migraine pathogenesis. Serum levels of CGRP are elevated during the migraine attack and return to normal with alleviation of pain. Intravenous injection of CGRP in migraineurs results in delayed headache similar to migraine. Since CGRP receptor antagonists lack direct vasoconstrictor activity, this therapeutic approach may offer advantages over the current mainstay of specific acute migraine treatment with 5-HT1B/1D receptor agonists (triptans), contra-indicated in patients with underlying cardiovascular disease. Intravenous BIBN4096BS (olcegepant) and oral MK-0974 (telcagepant), two CGRP-receptor antagonists, were safe and effective in the treatment of migraine attacks in Phase I and II trials. In a Phase III clinical trial, the efficacy of telcagepant 300 mg was comparable to that of zolmitriptan 5 mg. We intend to review the rationale for the use of CGRP-receptor antagonists, and to outline current developments and future perspectives.
A 10-b 125-MHz CMOS digital-to-analog converter (DAC) with threshold-voltage compensated current sources (1994)

This paper describes a 10-b high-speed COMS DAC fabricated by 0.8-/spl mu/m double-poly double-metal CMOS technology. In the DAC, a new current source called the threshold-voltage compensated current source is used in the two-stage current array to reduce the linearity error caused by inevitable current variations of the current sources. In the two-stage weighted current array, only 32 master and 32 slave unit current sources are required. Thus silicon area and stray capacitance can be reduced significantly. Experimental results show that a conversion rate of 125 MHz is achievable with differential and integral linearity errors of 0.21 LSB and 0.23 LSB, respectively. The power consumption is 150 mW for a single 5-V power supply. The rise/fall time is 3 ns and the full-scale settling time to /spl plusmn/1/2 LSB is within 8 ns. The chip area is 1.8 mm/spl times/1.0 mm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
GHMI: a general hypertext data model supporting integration of hypertext and information systems (1996)

We present a general hypertext data model supporting the integration (GHMI) of hypertext and information systems. The information systems benefit from hypertext functionality while preserving their computation capabilities. Although systems supporting integration of hypertext and display-oriented information systems do exist, no model or system effectively supports integrating hypertext and computation-oriented information systems (COISs). In COISs, content is generated and mapped dynamically at run-time. Based on the widely-recognized Dexter hypertext model, GHMI makes major contributions by significantly extending the Dexter model in the storage layer. GHMI divides its storage layer into two sublayers: a hypertext database and a hypertext knowledge base. The hypertext database extends the original Dexter storage layer regarding component classes, typed links, composite structures, typed anchors, and navigation structures. In the hypertext knowledge base, GHMI models domain mapping rules between hypertext and information systems called bridge laws.
Evaluation of the early processing routes of N-linked oligosaccharides of glycoproteins through the characterization of Man8GlcNAc2 isomers: evidence that endomannosidase functions in vivo in the absence of a glucosidase blockade (1996)

Since it has become apparent that the early processing of the N-linked oligosaccharides of glycoproteins can proceed by several routes, we undertook to determine whether the isomeric nature of Man8GlcNAc2, which is the first intermediate with the potential for structural diversity, can provide information relating to the pathways utilized in various intact cultured cells as well as in the total membrane fraction derived from these cells (BW5147.3, HepG2, HL60, F-9, and MDCK). With the use of kifunensine (KIF) to block processing by Golgi mannosidase I, it could be shown that a substantial amount of Man8GlcNAc2 components in which the terminal mannose is missing in the alpha 1,3-linked and alpha 1,6-linked chain (isomers A and C, respectively) are produced, although in the absence of the inhibitor only the B-isomer, in which the mannose of the middle chain has been excised, was apparent. Our findings in vivo and in vitro suggest that the distinctive Man8GlcNAc2 product of endomannosidase (isomer A) and of ER mannosidase II (isomer C) are not evident in the absence of KIF, since they are rapidly degraded by Golgi mannosidase I, which is located in an intracellular compartment distal to the other two enzymes and itself exclusively generates the Man8GlcNAc2 isomer B. Investigations carried out in HepG2 cells indicated that glycoproteins with N-linked oligosaccharides whose processing has been blocked by KIF at the Man8GlcNac2 isomer A and C stage can nevertheless be effectively secreted. The observation that isomer A of Man8GlcNAc2 is a specific product of endomannosidase action made it possible to demonstrate the action of this enzyme in vivo without employing a glucosidase blockade and to show that a substantial amount of the deglucosylation of N-linked oligosaccharides is carried out by this enzyme.
Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex (2008)

Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16 is a zinc-finger protein that controls brown fat determination by stimulating brown fat-selective gene expression, while suppressing the expression of genes selective for white fat cells. To determine the mechanisms regulating this switching of gene programs, we purified native PRDM16 protein complexes from fat cells. We show here that the PRDM16 transcriptional holocompex contains C-terminal-binding protein-1 (CtBP-1) and CtBP-2, and this direct interaction selectively mediates the repression of white fat genes. This repression occurs through recruiting a PRDM16/CtBP complex onto the promoters of white fat-specific genes such as resistin, and is abolished in the genetic absence of CtBP-1 and CtBP-2. In turn, recruitment of PPAR-gamma-coactivator-1alpha (PGC-1alpha) and PGC-1beta to the PRDM16 complex displaces CtBP, allowing this complex to powerfully activate brown fat genes, such as PGC-1alpha itself. These data show that the regulated docking of the CtBP proteins on PRDM16 controls the brown and white fat-selective gene programs.
Spleen volume and blood flow response to repeated breath-hold apneas (2003)

The purpose of this study was 1) to answer whether the reduction in spleen size in breath-hold apnea is an active contraction or a passive collapse secondary to reduced splenic arterial blood flow and 2) to monitor the spleen response to repeated breath-hold apneas. Ten trained apnea divers and 10 intact and 7 splenectomized untrained persons repeated five maximal apneas (A1-A5) with face immersion in cold water, with 2 min interposed between successive attempts. Ultrasonic monitoring of the spleen and noninvasive cardiopulmonary measurements were performed before, between apneas, and at times 0, 10, 20, 40, and 60 min after the last apnea. Blood flows in splenic artery and splenic vein were not significantly affected by breath-hold apnea. The duration of apneas peaked after A3 (143, 127, and 74 s in apnea divers, intact, and splenectomized persons, respectively). A rapid decrease in spleen volume ( approximately 20% in both apnea divers and intact persons) was mainly completed throughout the first apnea. The spleen did not recover in size between apneas and only partly recovered 60 min after A5. The well-known physiological responses to apnea diving, i.e., bradycardia and increased blood pressure, were observed in A1 and remained unchanged throughout the following apneas. These results show rapid, probably active contraction of the spleen in response to breath-hold apnea in humans. Rapid spleen contraction and its slow recovery may contribute to prolongation of successive, briefly repeated apnea attempts.
Biosynthesis of cis , cis -Muconic Acid and Its Aromatic Precursors, Catechol and Protocatechuic Acid, from Renewable Feedstocks by Saccharomyces cerevisiae (2012)

ABSTRACT Adipic acid is a high-value compound used primarily as a precursor for the synthesis of nylon, coatings, and plastics. Today it is produced mainly in chemical processes from petrochemicals like benzene. Because of the strong environmental impact of the production processes and the dependence on fossil resources, biotechnological production processes would provide an interesting alternative. Here we describe the first engineered Saccharomyces cerevisiae strain expressing a heterologous biosynthetic pathway converting the intermediate 3-dehydroshikimate of the aromatic amino acid biosynthesis pathway via protocatechuic acid and catechol into cis , cis -muconic acid, which can be chemically dehydrogenated to adipic acid. The pathway consists of three heterologous microbial enzymes, 3-dehydroshikimate dehydratase, protocatechuic acid decarboxylase composed of three different subunits, and catechol 1,2-dioxygenase. For each heterologous reaction step, we analyzed several potential candidates for their expression and activity in yeast to compose a functional cis , cis -muconic acid synthesis pathway. Carbon flow into the heterologous pathway was optimized by increasing the flux through selected steps of the common aromatic amino acid biosynthesis pathway and by blocking the conversion of 3-dehydroshikimate into shikimate. The recombinant yeast cells finally produced about 1.56 mg/liter cis , cis -muconic acid.
Optimal parametric feedforward estimation of frequency-selective fading radio channels (1994)

Estimation of time-varying dispersive radio channels is one of the most important tasks of receiver synchronisation. State-of-the-art adaptive estimators employing decision feedback suffer from error propagation and limited robustness against faster fading. In this paper, the optimal feedforward channel estimator using only known training symbols is systematically derived. Statistical channel information is assumed to be available. For moderately rapid fading channels (snapshot assumption), the optimal estimator is shown to be divided into the two subtasks of maximum-likelihood acquisition and subsequent Wiener filtering of the acquired quantities. If perfect training sequences resulting in optimal performance are used, the Wiener filtering operation collapses into independent filtering of the individual acquired tap estimates, and the resulting channel estimator becomes efficient and flexible. The performance of the optimal estimator is evaluated for important cases. A design example of a near-optimal HF channel estimator/receiver is discussed. Linear interpolation is used to reduce the computational complexity of receiver coefficient adjustment. Simulation results confirm the superiority and robustness of feedforward synchronization having near-optimal performance at reduced complexity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Humoral, mucosal, and cellular immunity in response to a human immunodeficiency virus type 1 immunogen expressed by a Venezuelan equine encephalitis virus vaccine vector (1997)

A molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE) has been genetically configured as a replication-competent vaccine vector for the expression of heterologous viral proteins (N. L. Davis, K. W. Brown, and R. E. Johnston, J. Virol. 70:3781-3787, 1996). The matrix/capsid (MA/CA) coding domain of human immunodeficiency virus type 1 (HIV-1) was cloned into the VEE vector to determine the ability of a VEE vector to stimulate an anti-HIV immune response in mice. The VEE-MA/CA vector replicated rapidly in the cytoplasm of baby hamster kidney (BHK) cells and expressed large quantities of antigenically identifiable MA/CA protein. When injected subcutaneously into BALB/c mice, the vector invaded and replicated in the draining lymphoid tissues, expressing HIV-1 MA/CA at a site of potent immune activity. Anti-MA/CA immunoglobulin G (IgG) and IgA antibodies were present in serum of all immunized mice, and titers increased after a second booster inoculation. IgA antibodies specific for MA/CA were detected in vaginal washes of mice that received two subcutaneous immunizations. Cytotoxic T-lymphocyte responses specific for MA/CA were detected following immunization with the MA/CA-expressing VEE vector. These findings demonstrate the ability of a VEE-based vaccine vector system to stimulate a comprehensive humoral and cellular immune response. The multifaceted nature of this response makes VEE an attractive vaccine for immunization against virus infections such as HIV-1, for which the correlates of protective immunity remain unclear, but may include multiple components of the immune system.
Parametric design and gridding through relational geometry (1995)

Relational Geometric Synthesis (RGS) is a new logical framework for building up precise definitions of complex geometric models from points, curves, surfaces and solids. RGS achieves unprecedented design flexibility by supporting a rich variety of useful curve and surface entities. During the design process, many qualitative and quantitative relationships between elementary objects may be captured and retained in a data structure equivalent to a directed graph, such that they can be utilized for automatically updating the complete model geometry following changes in the shape or location of an underlying object. Capture of relationships enables many new possibilities for parametric variations and optimization. Examples are given of panelization applications for submarines, sailing yachts, offshore structures, and propellers.
Characterization of distinct tethering and intracellular targeting domains in AKAP75, a protein that links cAMP-dependent protein kinase II beta to the cytoskeleton (1993)

Cyclic AMP-dependent protein kinase II beta (PKAII beta) is the principal mediator of cAMP action in neurons. A Kinase Anchor Proteins (AKAPs) are enriched in forebrain neurons and have distinct high affinity binding domains for the regulatory subunit (RII beta) of PKAII beta and components of the dendritic cytoskeleton. The selective accumulation of AKAP.RII beta complexes near dendritic microtubules tethers PKAII beta in proximity with adenylate cyclase in the synaptic plasma membrane and cytoskeletal proteins that are substrates for the kinase, thereby creating intraneuronal target sites for signals carried by cAMP. We have characterized the targeting (anchoring) and tethering (RII beta binding) domains of a prototypic anchor protein AKAP75. Deletion of N-terminal residues 27-48 generated a truncated RII beta-binding protein that partitions equally between the cytosol and detergent-insoluble fractions of HEK293 cells. Further removal of a non-adjacent sequence (residues 77-91) produced a cytosolic protein with unimpaired RII beta binding activity. Thus, two noncontiguous domains mediate the intracellular localization of AKAP75. Boundaries for the RII beta tethering domain were mapped to residues 392-413 by scanning mutagenesis. Residues containing long aliphatic side chains are essential for the high affinity binding of RII beta by AKAP75. Contributions of hydrophobic amino acids to tethering activity also depend on the position of the residue in the sequence. Certain conservative mutations that should not alter significantly the overall hydrophobicity or helicity of the tethering region (e.g. replacement of Leu with Ala) diminish the RII beta binding activity of AKAP75.
RECOMBINANT ONCOTOXIN AR209 (ANTI-P185 erbB-2 ) DIMINISHES HUMAN PROSTATE CARCINOMA XENOGRAFTS (1999)

This study provides preliminary evidence for the utility of a recombinant oncotoxin in the treatment of prostate carcinoma. Recombinant oncotoxins may be an effective clinical addition for the management of metastatic prostate lesions in patients treated with conventional therapy.
Fault detection with multiple observers (1993)

There is a pressing need for network management systems capable of handling faults. The use of a set of independent observers to detect faults in communication systems that are modeled by finite-state machines is proposed. An algorithm for constructing these observers and a fast real-time fault detection mechanism used by each observer are given. Since these observers run in parallel and independently, one immediate benefit is that of graceful degradation-one failed observer will not cause collapse of the fault management system. In addition, each observer has a simpler structure than the original system and can be operated at higher speed. This approach has the potential to be incorporated into the fault management system for a high-speed communication system.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sustained TCR Signaling Is Required for Mitogen-Activated Protein Kinase Activation and Degranulation by Cytotoxic T Lymphocytes (1998)

Requirements for T cell activation are not fully established. One model is that receptor occupancy and down-regulation are essential for activation, and another, not necessarily mutually exclusive, model is that sustained signals are important. Here we examine the importance of signal duration in T cell activation. First, we demonstrate that immobilized, but not soluble cross-linked, Abs to CD3 stimulate degranulation by CTL. The cross-linked Abs are not deficient in their ability to signal since they stimulate the same tyrosine phosphorylation pattern as immobilized Ab, but it is very transient relative to that stimulated by immobilized Ab. Furthermore, novel decreased migratory forms of Lck occur to a significant extent only after stimulation with immobilized Abs. A dramatic difference in the duration of signals is very evident when mitogen-activated protein kinase (MAPK) activity is examined. Immobilized anti-CD3 stimulates very high levels of MAPK activation that is still detectable 1 h after stimulation. In contrast, cross-linked Ab stimulates only transient and incomplete activation of MAPK. Taken together, these results suggest that TCR engagement and induction of tyrosine phosphorylation alone are not sufficient for T cell activation and that the duration of TCR-stimulated signals is critical to attain a functional response.
Directed Evolution of Pyruvate Decarboxylase-Negative Saccharomyces cerevisiae , Yielding a C 2 -Independent, Glucose-Tolerant, and Pyruvate-Hyperproducing Yeast (2004)

The absence of alcoholic fermentation makes pyruvate decarboxylase-negative (Pdc(-)) strains of Saccharomyces cerevisiae an interesting platform for further metabolic engineering of central metabolism. However, Pdc(-) S. cerevisiae strains have two growth defects: (i) growth on synthetic medium in glucose-limited chemostat cultures requires the addition of small amounts of ethanol or acetate and (ii) even in the presence of a C(2) compound, these strains cannot grow in batch cultures on synthetic medium with glucose. We used two subsequent phenotypic selection strategies to obtain a Pdc(-) strain without these growth defects. An acetate-independent Pdc(-) mutant was obtained via (otherwise) glucose-limited chemostat cultivation by progressively lowering the acetate content in the feed. Transcriptome analysis did not reveal the mechanisms behind the C(2) independence. Further selection for glucose tolerance in shake flasks resulted in a Pdc(-) S. cerevisiae mutant (TAM) that could grow in batch cultures ( micro (max) = 0.20 h(-1)) on synthetic medium, with glucose as the sole carbon source. Although the exact molecular mechanisms underlying the glucose-tolerant phenotype were not resolved, transcriptome analysis of the TAM strain revealed increased transcript levels of many glucose-repressible genes relative to the isogenic wild type in nitrogen-limited chemostat cultures with excess glucose. In pH-controlled aerobic batch cultures, the TAM strain produced large amounts of pyruvate. By repeated glucose feeding, a pyruvate concentration of 135 g liter(-1) was obtained, with a specific pyruvate production rate of 6 to 7 mmol g of biomass(-1) h(-1) during the exponential-growth phase and an overall yield of 0.54 g of pyruvate g of glucose(-1).
Adaptive control of a class of nonlinear discrete-time systems (1995)

We consider adaptive control via state feedback for a class of feedback linearizable discrete-time systems. To parallel the development in adaptive nonlinear continuous-time control, we employ a systematic procedure to design the controllers and the update laws for the so-called parametric-strict-feedback form and the parametric-pure-feedback form. The geometric conditions that characterize this class of systems are given. Depending on the growth conditions of the nonlinearities, global boundedness and convergence are achieved with various update laws. We also develop adaptive indirect schemes with an observer-based identifier for the parametric-strict-feedback form. As a result, the drawback of overparametrization in direct schemes can be removed.
In vivo accuracy of multisequence MR imaging for identifying unstable fibrous caps in advanced human carotid plaques (2003)

Multisequence MRI can accurately characterize the in vivo state of the fibrous cap. This finding supports the use of these noninvasive techniques to prospectively identify vulnerable plaques.