gebhart/patrepeval huggingface dataset:
Synthesis and Biological Evaluation of 4-(Hydroxyalkyl)estradiols and Related Compounds (1997)

A series of synthetic estrogens containing hydroxyalkyl side chains at the C-4 position of the A ring were designed as metabolically stable analogs of 4-hydroxyestradiol, a catechol estrogen. These synthetic steroids would facilitate investigations on the potential biological role of catechol estrogens and also enable further examination of the structural and electronic constraints on the A ring in the interaction of estrogens with the estrogen receptor. Catechol estrogens are implicated as possible causative agents in estrogen-induced tumorigenesis. 4-Hydroxyestradiol has weaker affinity for the estrogen receptor and exhibits lower estrogenic activity in vivo; on the other hand, the catechol estrogens are prone to further oxidative metabolism and can form reactive intermediates. This report describes the synthesis and initial biochemical evaluation of 4-(hydroxyalkyl)estrogens and 4-(aminoalkyl)estradiols. The 4-(hydroxyalkyl)estrogens were prepared by oxidative hydroboration of 4-alkenylestradiols. The alkenylestradiols were obtained via a Stille cross-coupling between a MOM-protected 4-bromoestradiol and an alkenylstannane. The (4-aminoalkyl)estrogens were prepared from the hydroxyalkyl derivatives with phthalimide under Mitsunobu conditions. The substituted estradiols were evaluated for estrogen receptor binding activity in MCF-7 human mammary carcinoma cells, and 4-(hydroxymethyl)estradiol 1 exhibited the highest affinity with an apparent EC50 value of 364 nM. The relative activities for mRNA induction of the pS2 gene in MCF-7 cell cultures by the 4-(hydroxyalkyl)estrogens closely parallel the relative binding affinities. 4-(Hydroxymethyl)estradiol 1 did not stimulate the growth of MCF-7 cells at concentrations up to 1 microM. Thus, 4-(hydroxymethyl)estradiol 1 exhibited similar estrogen receptor affinity as the catechol estrogen, 4-hydroxyestradiol, and may prove useful in the examination of the biological effects of 4-hydroxyestrogens.
Attenuated Bordetella pertussis BPZE1 protects against allergic airway inflammation and contact dermatitis in mouse models (2012)

Our study demonstrates the broad anti-inflammatory properties of the attenuated B. pertussis BPZE1 vaccine candidate and supports its development as a promising agent to prevent and/or treat allergic diseases.
Evidence that less-than-full-length pol gene products are functional in hepadnavirus DNA synthesis (1991)

Duck hepatitis B virus mutants containing frameshift or stop codon mutations in a portion of the viral pol gene separating the terminal protein and reverse transcriptase domains had a leaky phenotype and, depending on the location and type of mutation, synthesized up to 10% as much viral DNA as did the wild type. This region of the pol gene had previously been reported to be refractory to missense mutations; in fact, the leakiness of most of our mutants appeared attributable to translational suppression, which would also be expected to introduce amino acid changes. However, at least one mutant (pH1093 + 2), which was ca. 10% as active as the wild type, appeared to use a novel pathway to express the viral pol gene. Our analyses indicated that pH1093 + 2 synthesized the viral reverse transcriptase as a fusion protein with the amino-terminal portion of the pre-S envelope protein. Thus, in this case, the products of the terminal-protein and reverse transcriptase domains of the pol gene would function as separate protein species, though perhaps noncovalently joined in a dimeric structure during assembly of DNA replication complexes. Evidence was also obtained that was consistent with the idea that the wild-type pol gene may, at least in certain instances, be expressed as functional, subgenic polypeptides.
Mechanistic studies on the human matrix metalloproteinase stromelysin (1992)

To probe the mechanism of stromelysin (SLN)-catalyzed peptide hydrolysis, we determined the pH dependence of kc/Km and solvent deuterium isotope effects on kc and kc/Km. pH dependencies of kc/Km were determined for the SLN-catalyzed hydrolysis of three peptides: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Nle-NH2,Arg-Pro-Ala-Pro-Gln-Gln- Phe-Phe - Gly-Leu-NleNH2, and N-acetyl-Arg-Pro-Ala-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Nle-NH2 (cleavage at Gln-Phe bond). The pH dependencies are all bell-shaped with shoulders that extend from pH 7.5 to 8.5. The existence of a shoulder indicates that the reaction mechanism involves at least two routes to products. These curves are governed by three proton ionizations with pKa values of 5.4, 6.1, and 9.5. The solvent isotope effect measurements provided the following values: D(kc/Km) = 0.80 +/- 0.05 and D(kc) = 1.58 +/- 0.05. That D(kc/Km) and D(kc) are different suggests that the rate-limiting transition states for the processes governed by kc/Km and kc cannot be the same. We use these results, together with analogy to thermolysin catalysis, to develop a mechanism for SLN catalysis.
High Rates of Fatty Acid Oxidation during Reperfusion of Ischemic Hearts Are Associated with a Decrease in Malonyl-CoA Levels Due to an Increase in 5’-AMP-activated Protein Kinase Inhibition of Acetyl-CoA Carboxylase (1995)

We determined whether high fatty acid oxidation rates during aerobic reperfusion of ischemic hearts could be explained by a decrease in malonyl-CoA levels, which would relieve inhibition of carnitine palmitoyl-transferase 1, the rate-limiting enzyme involved in mitochondrial uptake of fatty acids. Isolated working rat hearts perfused with 1.2 mM palmitate were subjected to 30 min of global ischemia, followed by 60 min of aerobic reperfusion. Fatty acid oxidation rates during reperfusion were 136% higher than rates seen in aerobically perfused control hearts, despite the fact that cardiac work recovered to only 16% of pre-ischemic values. Neither the activity of carnitine palmitoyltransferase 1, or the IC50 value of malonyl-CoA for carnitine palmitoyl-transferase 1 were altered in mitochondria isolated from aerobic, ischemic, or reperfused ischemic hearts. Levels of malonyl-CoA were extremely low at the end of reperfusion compared to levels seen in aerobic controls, as was the activity of acetyl-CoA carboxylase, the enzyme which produces malonyl-CoA. The activity of 5'-AMP-activated protein kinase, which has been shown to phosphorylate and inactivate acetyl-CoA carboxylase in other tissues, was significantly increased at the end of ischemia, and remained elevated throughout reperfusion. These results suggest that accumulation of 5'-AMP during ischemia results in an activation of AMP-activated protein kinase, which phosphorylates and inactivates ACC during reperfusion. The subsequent decrease in malonyl-CoA levels wil result in accelerated fatty acid oxidation rates during reperfusion of ischemic hearts.
Improved Computational Methods for Ray Tracing (1984)

This paper describes algorithmic procedures that have been implemented to reduce the computational expense of producing ray-traced images. The selection of bounding volumes is examined to reduce the computational cost of the ray-intersection test. The use of object coherence, which relies on a hierarchical description of the environment, is then presented. Finally, since the building of the rayintersection trees is such a large portion of the computation, a method using image coherence is described. This visible-surface preprocessing method, which is dependent upon the creation of an "item buffer," takes advantage of a priori image information. Examples that indicate the efficiency of these techniques for a variety of representative environments are presented.
Tissue distribution of bupivacaine enantiomers in sheep (1993)

rac-Bupivacaine HCl was infused intravenously to constant arterial blood drug concentrations in sheep using a regimen of 4 mg/min for 15 min followed by 1 mg/min to 24 h. At 24 h, arterial blood was sampled, the animal was killed with a bolus of KCl solution, then rapidly dissected and samples were obtained from heart, brain, lung, kidney, liver, muscle, fat, gut, and rumen. Tissue:blood distribution coefficients for (+)-(R)-bupivacaine exceeded those of (-)-(S)-bupivacaine (P < 0.05) for heart, brain, lung, fat, gut, and rumen by an overall mean of 43%. Blood:plasma distribution coefficients of (-)-(S)-bupivacaine exceeded those of (+)-(R)-bupivacaine by a mean of 29% and this offset the tissue:blood distribution coefficients so that the previously significant enantioselective differences disappeared. It is concluded that although enantioselectivity of bupivacaine distribution is shown by the measured tissue:blood distribution coefficients, it is not shown when tissue:plasma water distribution coefficients are calculated, suggesting that there is no intrinsic difference between the bupivacaine enantiomers in tissue affinity. Sheep given fatal intravenous bolus doses of rac-bupivacaine had significantly greater concentrations of (+)-(R)-bupivacaine than (-)-(S)-bupivacaine in brain (P = 0.028) and ventricle (P = 0.036); these could augment the greater myocardial toxicity of this enantiomer found in vitro.
Clinical Aspects of Growth Hormone Deficiency in Adults (1995)

GRADUALLY it is being realized that GH may have important physiological functions in adult man. Until recently, GH was only used to treat short statured children with established GH deficiency (GHD), and it remains common practice to discontinue GH replacement therapy when final height is reached. From a physiological point of view, it is questionable whether this approach is appropriate since it is well known that GH secretion persists throughout life (1–5). Daily GH production reaches its maximum during puberty (3–5). Thereafter, the GH secretion rate gradually decreases with age (3). Recently, several studies have shown that GHD in adults is associated with abnormalities in body composition (6–14), metabolic derangements (15–17), and suboptimal physical performance (18–20). Since recombinant technology has solved the limitations in GH supply, policies concerning GH replacement therapy in man may now be reconsidered. The studies performed in GHD adults uniformly suggest that these patients benefit from GH replacement therapy (19–34). However, it has also become clear that GH substitution is not without side effects. The purpose of this review is to describe and analyze the reported findings in untreated GHD adults as well as to evaluate the effects and side effects of GH replacement therapy. The pharmacological aspects of GH treatment in GHD subjects have been addressed recently (35).
Mouse Dendritic Cells Express the P2X7 Purinergic Receptor: Characterization and Possible Participation in Antigen Presentation (1999)

Immune cells express P2 purinoceptors of the P2Y and P2X subtypes. In the present work, we show that three dendritic cell (DC) lines, D2SC/1, CB1, and FSDC, representative of immature DCs, express the P2X7 (formerly P2Z) receptor, as judged from RT-PCR amplification, reactivity to a specific antiserum, and pharmacological and functional evidence. Receptor expression is higher in FSDC cells, a cell line that is functionally more mature than D2SC/1 and CB1. From the wild-type DC population, we selected cell clones lacking the P2X7R (P2X7less). We also used a P2XR blocker, oxidized ATP, to irreversibly inhibit the P2X7R. Ability of P2X7less FSDCs or of oxidized ATP-inhibited FSDCs to stimulate Ag-specific TH lymphocytes was severely decreased although Ag endocytosis was minimally affected. During coculture with TH lymphocytes, wild-type FSDC secreted large amounts of IL-1beta. Release of this cytokine was reduced in P2X7less DCs. These data show that DCs express the P2X7 purinoceptor and suggest a correlation between P2X7R expression and Ag-presenting activity.
Perioperative treatment of patients with sepsis (2013)

Recent high-quality trials in the intensive care setting have provided data to improve the treatment and thereby the outcome of patients with sepsis. These findings may be used in the perioperative setting to minimize the harmful effects of specific interventions.
Effects of lactate concentration on hybridoma culture in lactate‐controlled fed‐batch operation (1992)

To investigate the effects of lactate on cell growth and antibody production, a new method of maintaining the lactate concentration constant in a fed-batch culture is described. When the pH was initially adjusted by sodium hydroxide, the specific growth rate decreased and specific death rate increased with an increase of lactate concentration. To investigate whether the inhibition was due to the lactate concentration itself or to the osmotic pressure, the effect of the osmotic pressure adjusted by sodium chloride was compared with that of sodium lactate. When the osmotic pressure was adjusted to same condition as that of sodium lactate using sodium chloride, the specific growth data showed the same degree of growth inhibition. It was thus evident that the inhibition to cell growth was mainly due to osmotic pressure while lactate production from glucose was found to be inhibited by the lactate itself compared with sodium chloride. The specific antibody production rate had a maximum value within a certain range of lactate concentration. Moreover, specific antibody production rate had a unified relationship with the kinetic parameter mu, in spite of the different causes of inhibition by lithium lactate and sodium lactate. A certain "trade-off" relationship between growth and antibody production existed at higher growth rates.
[In vitro and in vivo biodegradation of sustained-release vehicle poloxamer 407 in situ gel]. (2008)

Poloxamer 407 biodegraded slowly, but it could be biodegraded in vivo or discharged via eustachian tube, and caused no inflammation and immunologic rejection on the middle ear cavity. Thus, poloxamer 407 gel is suitable for the short-time sustained-release medical treatment in the inner ear diseases.
Neural network implementation using self-lensing media (1995)

An all-optical implementation of a feed-forward artificial neural network is presented that uses self-lensing materials in which the index of refraction is irradiance dependent. Many of these types of material have ultrafast response times and permit both weighted connections and nonlinear neuron processing to be implemented with only thin material layers separated by free space. Both neuron processing and weighted interconnections emerge directly from the physical optics of the device. One creates virtual neurons and their connections simply by applying patterns of irradiance to thin layers of the nonlinear media. This is a result of a variation of the refractive-index profile of the self-lensing nonlinear media in response to the applied irradiance. An optical-backpropagation training method for this network is presented. The optical backpropagation is a training method that can be implemented potentially within the same optical device as the forward calculations, although several issues crucial to this po sibility remain to be addressed. Such a network was numerically simulated and trained to solve many benchmark classification problems, and some of these results are presented. To demonstrate the feasibility of building such a network, we also describe experimental work in the construction of an optical network trained to perform a logic XNOR function. This network, as a proof of concept, uses a relatively slow thermal nonlinear material with ~1-s response time.
Immunization against tumor cell surface complement-regulatory proteins. (2001)

Complement is an enzymatic cascade that results in the release of pro-inflammatory anaphylatoxins, C3b deposition and the assembly of the membrane attack complex (MAC), which results in cell lysis. Cells express complement regulatory proteins or inhibitors to protect themselves from bystander attack by complement. Expression of the complement-regulatory proteins CD55, CD46 and CD59 are deregulated in cancer with tumors showing loss of one or more inhibitors and strong overexpression of others. This results in tumors that are resistant to attack by complement and is a major limitation in the use of monoclonal antibodies as monotherapies. However, tumor sensitivity to complement can be restored by co-administration of antibodies that bind to the functional domains of complement-regulatory proteins. Overexpression of complement-regulatory proteins on tumors also makes them potential targets for cancer vaccines. However, these vaccines have to be carefully designed to induce immune responses that recognize inhibitors overexpressed on tumors and that do not detect the levels expressed by normal cells. A human anti-idiotypic antibody that mimics CD55 has been used successfully in over 200 colorectal cancer and osteosarcoma patients. 70% Of patients show CD55-specific immune responses with no associated toxicity. Similar vaccines targeting CD46 and CD59 would eliminate any cell overexpressing a complement inhibitor. Any remaining tumor cell or any tumor cell that loses complement-regulatory proteins in response to therapy would become highly susceptible to in situ complement deposition. In summary, targeting complement-regulatory proteins is a very attractive approach to tumor therapy, although great care must be taken in preventing normal tissue recognition as this could lead to uncontrolled complement deposition and massive cell lysis.
CD36 is a receptor for oxidized high density lipoprotein: Implications for the development of atherosclerosis (2007)

Atherosclerotic plaques result from the excessive deposition of cholesterol esters derived from lipoproteins and lipoprotein fragments. Tissue macrophage within the intimal space of major arterial vessels have been shown to play an important role in this process. We demonstrate in a transfection system using two human cell lines that the macrophage scavenger receptor CD36 selectively elicited lipid uptake from Cu(2+)-oxidized high density lipoprotein (HDL) but not from native HDL or low density lipoprotein (LDL). The uptake of oxHDL displayed morphological and biochemical similarities with the CD36-dependent uptake of oxidized LDL. CD36-mediated uptake of oxidized HDL by macrophage may therefore contribute to atheroma formation.
An object oriented visual programming language toolkit (1995)

article An object oriented visual programming language toolkit Share on Authors: Mark Young View Profile , Danielle Argiro View Profile , Jeremy Worley View Profile Authors Info & Claims ACM SIGGRAPH Computer GraphicsVolume 29Issue 2May 1995 pp 25–28https://doi.org/10.1145/204362.204368Online:01 May 1995Publication History 13citation185DownloadsMetricsTotal Citations13Total Downloads185Last 12 Months4Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Linoleic acid supplemention of Barth syndrome fibroblasts restores cardiolipin levels: implications for treatment (2003)

The object of this study was to investigate whether the levels of cardiolipin in cultured skin fibroblasts of patients with Barth syndrome (BTHS) can be restored by addition of linoleic acid to growth media. To this end, fibroblasts from controls and BTHS patients were grown in the presence or absence of linoleic acid. High-performance liquid chromatography-electrospray ionization tandem mass spectrometry was used for quantitative and compositional analysis of cardiolipin. Incubation of cells from both BTHS and controls with different concentrations of linoleic acid led to a dose- and time-dependent increase of cardiolipin levels. The increased levels of cardiolipin in fibroblasts of BTHS patients after treatment with linoleic acid indicate that an increased amount of linoleic acid in the diet might be beneficial to BTHS patients.
Graphs over time (2005)

How do real graphs evolve over time? What are "normal" growth patterns in social, technological, and information networks? Many studies have discovered patterns in static graphs, identifying properties in a single snapshot of a large network, or in a very small number of snapshots; these include heavy tails for in- and out-degree distributions, communities, small-world phenomena, and others. However, given the lack of information about network evolution over long periods, it has been hard to convert these findings into statements about trends over time.Here we study a wide range of real graphs, and we observe some surprising phenomena. First, most of these graphs densify over time, with the number of edges growing super-linearly in the number of nodes. Second, the average distance between nodes often shrinks over time, in contrast to the conventional wisdom that such distance parameters should increase slowly as a function of the number of nodes (like O(log n) or O(log(log n)).Existing graph generation models do not exhibit these types of behavior, even at a qualitative level. We provide a new graph generator, based on a "forest fire" spreading process, that has a simple, intuitive justification, requires very few parameters (like the "flammability" of nodes), and produces graphs exhibiting the full range of properties observed both in prior work and in the present study.
Controlling the cell cycle: The role of calcium/calmodulin-stimulated protein kinases I and II (2011)

Many studies have implicated Ca²+ and calmodulin (CaM) as regulators of the cell cycle. Ca²+/CaM-stimulated proteins, including the family of multifunctional Ca²+/CaM-stimulated protein kinases (CaMK), have also been identified as mediators of cell cycle progression. CaMKII is the best-characterized member of this family, and is regulated by multi-site phosphorylation and targeting. Using pharmacological inhibitors that were believed to be specific for CaMKII, CaMKII has been implicated in every phase of the cell cycle. However, these 'specific' inhibitors also produce effects on other CaMKs. These additional effects are usually ignored, and the effects of the inhibitors are normally attributed to CaMKII without further investigation. Using new specific molecular techniques, it has become clear that CaMKI is an important regulator of G₁, whereas CaMKII is essential for regulating G₂/M and the metaphase-anaphase transition. If the mechanisms controlling these events can be fully elucidated, new targets for controlling proliferative diseases may be identified.
<title>High-precision low-cost colorimeters and spectrophotometers based on liquid crystalline optics</title> (2004)

As the phenomenon "color" is involved in almost each production where is a great demand for inexpensive and precise colorimeters. Today there are in principle two kinds of colorimeters: three-channel colorimeters (which are cheap but not accurate) and array spectrometers (which offer a high accuracy at a high price). Liquid crystals have the potential to allow accurate color measurements at a low price. We show three different schemes of colorimeters and actual measurements. The accuracy of our colorimeters is better than 0.005 for each color coordinate.
HTML5 and CSS3 Responsive Web Design Cookbook (2013)

As a Cookbook, we are targeting existing developers who need to pick and choose specific recipes in order to help their websites become accessible (and usable) regardless of screen size, device, or browser.HTML5 and CSS3 Responsive Web Design Cookbook, for all of today's wireless Internet devices, is for web developers seeking innovative techniques that deliver fast, intuitive interfacing for the latest mobile Internet devices.