gebhart/patrepeval huggingface dataset:
Agonist analysis of 2‐(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells (1992)

1. 2-(Carboxycyclopropyl)glycines (CCGs) are conformationally restricted glutamate analogues and consist of eight isomers including L- and D-forms. The agonist potencies and selectivities of these compounds for metabotropic glutamate receptors (mGluRs) were studied by examining their effects on the signal transduction of representative mGluR1, mGluR2 and mGluR4 subtypes in Chinese hamster ovary cells expressing the individual cloned receptors. 2. Two extended isomers of L-CCG, L-CCG-I and L-CCG-II, effectively stimulated phosphatidylinositol hydrolysis in mGluR1-expressing cells. The rank order of potencies of these compounds was L-glutamate > L-CCG-I > L-CCG-II. 3. L-CCG-I and L-CCG-II were effective in inhibiting the forskolin-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in mGluR2-expressing cells. Particularly, L-CCG-I was a potent agonist for mGluR2 with an EC50 value of 3 x 10(-7) M, which was more than an order of potency greater than that of L-glutamate. 4. L-CCG-I evoked an inhibition of the forskolin-stimulated cyclic AMP production characteristic of mGluR4 with a potency comparable to L-glutamate. 5. In contrast to the above compounds, the other CCG isomers showed no appreciable effects on the signal transduction involved in the three mGluR subtypes. 6. This investigation demonstrates not only the importance of a particular isomeric structure of CCGs in the interaction with the mGluRs but also a clear receptor subtype specificity for the CCG-receptor interaction, and indicates that the CCG isomers would serve as useful agonists for investigation of functions of the mGluR family.
Safety and tolerability of fentanyl iontophoretic transdermal system: Findings from a pooled data analysis of four clinical trials (2011)

Acute postoperative pain remains inadequately managed. Although patient-controlled analgesia (PCA) represents a significant advance in postoperative pain management, drawbacks may include invasiveness and the potential for programming errors. The analysis presented here is based on pooled patient-level safety data from four multicenter, randomized, active-controlled trials that evaluated the safety and tolerability of the needle-free, preprogrammed fentanyl HCl iontophoretic transdermal system (ITS) versus morphine intravenous PCA for postoperative pzin management; the results for patients who received fentanyl ITS are presented here. Adverse events (AEs), serious AEs, and clinically relevant respiratory depression were assessed across patient subpopulations categorized by age. A total of 1288 patients, including 356 elderly (>65 years of age) patients, received fentanyl ITS following surgery. The most commonly reported AEs included nausea, fever, vomiting, headache, anemia, pruritus, and hypotension. The incidence of AEs was generally lower for elderly patients than for patients 65 years or younger. Application-site reactions were reported for 18.6 percent of patients using fentanyl ITS and were generally mild to moderate in severity. No cases of clinically relevant respiratory depression were reported for patients who received fentanyl ITS. The results demonstrate that fentanyl ITS is safe and well tolerated for postoperative pain management for patients overall and for subpopulations divided according to age.
1/f noise in bismuth ruthenate based thick-film resistors (1997)

We report measurements of 1/f noise in bismuth ruthenate (Bi/sub 2/Ru/sub 2/O/sub 7/) thick-film resistors in the frequency range of 1 Hz to 40 kHz including the dependence of the noise on the bias current, resistance in the range 1 k/spl Omega/ to 400 k/spl Omega/ and laser trimming effects. The noise spectra show that the magnitude of the noise parameterized by the relative noise index parameter C has the approximate dependence given by C=3/spl times/10/sup -15/ (R/sub s/n/sub s/)/sup 0.6/, where n/sub s/ is the aspect ratio and R/sub s/ is the sheet resistance. Technologically this is an important result since it allows the prediction of the approximate level of noise for any resistor made from the BIROX series compounds from the ink resistivity and the dimensions of the resistor. The link between the noise magnitude and noise models is examined.
Development of enteric neuron diversity (2009)

The mature enteric nervous system (ENS) is composed of many different neuron subtypes and enteric glia, which all arise from the neural crest. How this diversity is generated from neural crest-derived cells is a central question in neurogastroenterology, as defects in these processes are likely to underlie some paediatric motility disorders. Here we review the developmental appearance (the earliest age at which expression of specific markers can be localized) and birthdates (the age at which precursors exit the cell cycle) of different enteric neuron subtypes, and their projections to some targets. We then focus on what is known about the mechanisms underlying the generation of enteric neuron diversity and axon pathfinding. Finally, we review the development of the ENS in humans and the etiologies of a number of paediatric motility disorders.
Polarized Light Emission from Nonpolar InGaN Light-Emitting Diodes Grown on a Bulk m-Plane GaN Substrate (2005)

Polarized light emission from (1010) m -plane InGaN/GaN light-emitting diodes has been observed and analyzed in relation to the valence band structure in nonpolar InGaN/GaN quantum wells. Electroluminescence along the &lt;1100&gt; direction out of the m -plane was partially polarized in the &lt;1120&gt; direction, with a polarization ratio of 0.17. This polarized light emission exhibited a spectral peak at 2.69 eV, which has been attributed to the transition between the conduction band and the heavy hole subband with p x atomic orbital-like character due to the inhomogeneous biaxial strain in the device structure. Weak polarized emission in the &lt;0001&gt; direction was also observed, with a spectral peak at the higher energy of 2.78 eV. The transition between the conduction band and the crystal-field split-off subband is believed to be responsible for the &lt;0001&gt; polarized light emission.
Bone Density in Amenorrheic Women with and without Hyperprolactinemia* (1983)

To determine whether decreased bone density in patients with PRL-secreting pituitary tumors is specifically related to hyperprolactinemia or is a consequence of disordered pituitary-gonadal function common to all amenorrheic states, we measured the bone mineral content of the radius by photon absorptiometry in normal subjects, in women with amenorrhea and normal serum PRL levels, and in women with PRL-secreting pituitary tumors. The women did not differ significantly in mean age, height, weight, or serum calcium, phosphorous, gonadotropin, testosterone, vitamin D, or PTH concentrations, and all had normal renal and thyroid function. The bone mineral content in women with amenorrhea and normal serum PRL levels (0.91 +/- 0.02 g/cm) was not significantly different from that in control subjects (0.88 +/- 0.01 g/cm). Patients with PRL-secreting tumors studied 2-5 yr after transsphenoidal surgery had significantly diminished bone mineral content whether they were cured (0.82 +/- 0.02 g/cm) or had persistent amenorrhea and hyperprolactinemia (0.81 +/- 0.02 g/cm). Serum estradiol concentrations did not differ significantly in the four groups, and there was no correlation between estradiol concentration and bone mineral content or between PRL concentration and bone mineral content in the amenorrheic women. The presence of decreased bone mineral content in hyperprolactinemic patients suggests that PRL may have a direct effect on bone and may be another indication for early treatment of PRL-secreting pituitary tumors.
Hyaluronidase ameliorates rejection-induced edema (1999)

Hyaluronan, a glucosaminoglycan with unique water-binding capacity, is accumulated in the interstitial edematous tissue in rejecting organs. We here investigated whether the increased tissue content of water and hyaluronan seen during allograft rejection can be prevented by treatment with the hyaluronan-degrading enzyme hyaluronidase. Heterotopic heart transplantations between PVG and Wistar/Kyoto rats were performed. Recipient rats were treated with hyaluronidase prophylactically or therapeutically, either alone or in combination with cyclosporine. Daily intravenous injections of hyaluronidase induced a significant reduction of the cardiac content of both hyaluronan and water, as evaluated on day six after transplantation. Morphological examination revealed grafts with better preserved morphology and fewer infiltrating mononuclear cells, compared to untreated controls. Hyaluronidase therapy, alone or combined with cyclosporine, resulted in prolonged graft survival times. Hyaluronidase infusion for two hours also reduced already established edema five days after transplantation. This study confirms the hypothesis that hyaluronan accumulation plays a critical role in edema formation, and that hyaluronidase therapy can be used to reduce edema after organ transplantation.
Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells (2011)

Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c(+) cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α(+) dendritic cells, which were demonstrated to be essential using Batf3(-/-) mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α(+) DCs.
Evaluation of ricin A chain-containing immunotoxins directed against glycolipid and glycoprotein on mouse lymphoma cells. (1994)

Immunotoxins composed of monoclonal antibodies (mAbs) and various toxins have been developed for the treatment of malignancies. We investigated the efficacy of three ricin toxin A-chain (RTA)-containing immunotoxins (ITs) conjugated from mAbs which recognize glycolipid asialo-GM2 and glycoprotein H-2d. These ITs retained the same immunoreactivity with mAbs. We evaluated the cytotoxicity of these ITs against mouse lymphoma cells L5178Y variants showing high (AA12,CC9) and low (27AV) expression of asialo-GM2. Anti-H-2d-RTA IT had the strongest cytotoxicity for all cell lines. Anti-asialo-GM2 (IgM)-RTA IT had stronger cytotoxicity than anti-asialo-GM2 (IgG3)-RTA IT. Anti-asialo-GM2-RTA ITs had different cytotoxicity against AA12 and CC9 cells. The establishment of appropriate anti-glycolipid mAbs may lead to effective immunotargeting therapy.
Biomarkers in Lung Cancer: From Early Detection to Novel Therapeutics and Decision Making (2008)

Lung cancer remains a significant cause of mortality worldwide. While advances in therapy continue to be made, the overall prognosis for patients diagnosed with lung cancer remains poor. Historically, markers such as age, performance status and disease stage have been used to risk-stratify patients and guide therapeutic decisions. These parameters provide some useful information, but more sensitive markers are clearly needed. Molecular and genetic studies have identified several such markers, which appear to play critical roles in carcinogenesis and affect patient outcomes. This article reviews a number of biomarkers that have been identified in lung cancer, and their prognostic and predictive roles.
Stoichiometric Relationships Between Endothelial Tetrahydrobiopterin, Endothelial NO Synthase (eNOS) Activity, and eNOS Coupling in Vivo (2005)

Endothelial dysfunction in vascular disease states is associated with reduced NO bioactivity and increased superoxide (O2*-) production. Some data suggest that an important mechanism underlying endothelial dysfunction is endothelial NO synthase (eNOS) uncoupling, whereby eNOS generates O2*- rather than NO, possibly because of a mismatch between eNOS protein and its cofactor tetrahydrobiopterin (BH4). However, the mechanistic relationship between BH4 availability and eNOS coupling in vivo remains undefined because no studies have investigated the regulation of eNOS by BH4 in the absence of vascular disease states that cause pathological oxidative stress through multiple mechanisms. We investigated the stoichiometry of BH4-eNOS interactions in vivo by crossing endothelial-targeted eNOS transgenic (eNOS-Tg) mice with mice overexpressing endothelial GTP cyclohydrolase 1 (GCH-Tg), the rate-limiting enzyme in BH4 synthesis. eNOS protein was increased 8-fold in eNOS-Tg and eNOS/GCH-Tg mice compared with wild type. The ratio of eNOS dimer:monomer was significantly reduced in aortas from eNOS-Tg mice compared with wild-type mice but restored to normal in eNOS/GCH-Tg mice. NO synthesis was elevated by 2-fold in GCH-Tg and eNOS-Tg mice but by 4-fold in eNOS/GCH-Tg mice compared with wild type. Aortic BH4 levels were elevated in GCH-Tg and maintained in eNOS/GCH-Tg mice but depleted in eNOS-Tg mice compared with wild type. Aortic and cardiac O2*- production was significantly increased in eNOS-Tg mice compared with wild type but was normalized after NOS inhibition with Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME), suggesting O2*- production by uncoupled eNOS. In contrast, in eNOS/GCH-Tg mice, O2*- production was similar to wild type, and L-NAME had no effect, indicating preserved eNOS coupling. These data indicate that eNOS coupling is directly related to eNOS-BH4 stoichiometry even in the absence of a vascular disease state. Endothelial BH4 availability is a pivotal regulator of eNOS activity and enzymatic coupling in vivo.
A 1,3‐Diboratacyclobutadiene and Its Dimer, a Sandwich Compound with a Li4Layer (1986)

The synthesis, charge distribution, and reactions of 1 (RC(CH3)3, R′Si(CH3)3), the simplest organometallic cyclobutadiene so far, are described. The results of NMR spectroscopy underline the importance of the resonance structures 1 for the description of the electron distribution.
Low complexity algorithm for rate and power quantization in extended V-BLAST (2002)

Using multiple antennas at both the transmitter and receiver, BLAST exploits the multipath characteristics of a wireless channel to enable very large capacities. In an extended V-BLAST, those capacities are approached with single-dimensional coding and rate adaptation. However, such results require infinite precision for rate and power, which is not implementable due to a limited data rate on the feedback channel. We show that discretizing the rates to QAM constellations causes a 3-5 dB penalty. We then propose SQPC (successive quantization with power control), an ad-hoc low-complexity algorithm that reduces that penalty to 1-3 dB. We show that SQPC closely approaches the performance limit attainable with discrete QAM rates, which we find numerically by exhaustive search.
Mechanics of C60 in Nanotubes (2001)

A modeling study of C60 in nanotubes is presented, with focus on a new approach. We report on the elastic properties, energetics, and certain tribological issues, for C60 inside (n, n) nanotubes, with n ranging from 5 to 10. A new combined molecular dynamics/continuum approach with account of both the nonbonded and bonded interactions was used. The elastic properties of the nanotube were analytically derived on the basis of the Tersoff-Brenner potential. The derived Young's modulus is consistent with experimental values. We have computed the case where the C60 has zero initial velocity and is “sucked” into the (10, 10) or (9, 9) tubes due to the sharp force gradient present from the deep attractive potential at the tube inlet; C60 then oscillates back and forth inside the (10, 10) and (9, 9) nanotubes. C60 seems to make a perfect nanobearing system when in the (10, 10) tube. In a separate modeling study, C60 was fired on axis at high velocity (from 400 up to 1600 m/s) toward the six different armchair nanotubes. Over this velocity range the C60 could only penetrate into the (10, 10) and (9, 9) nanotubes, rebounding from the (8, 8), (7, 7), (6, 6), and (5, 5) tubes.
Green Diesel: A Second Generation Biofuel (2007)

Environmentally-conscious design of processes and products is increasingly viewed as an important strategy in the sustainable development of new refining and chemical processes. This paper discusses a new process technology developed by UOP and Eni S.p.A; the UOP/Eni EcofiningTM process to produce green diesel from vegetable oil. This novel process utilizes catalytic saturation, hydrodeoxygenation, decarboxylation and hydroisomerization reactions to produce an isoparaffin-rich diesel fuel from renewable feedstock containing triglycerides and fatty acids. The resultant biofuel product has a high cetane value, a lower gravity, good cold flow properties and excellent storage stability. Green diesel is completely compatible for blending with the standard mix of petroleum-derived diesel fuels, thus providing significant value to the refiner. The process for producing green diesel operates at mild operating conditions and integrates well within existing petroleum refineries. In contrast to fatty acid methyl esters, where fuel properties depend on feed origin and process configuration, green diesel product is independent of feed origin and the fully deoxygenated biofuel is readily blended with conventional diesel fuel. A life cycle assessment (LCA) of this promising new biofuel production technology has been undertaken to quantify the intrinsic benefits of green diesel production over the current practice of converting various forms of lipids to fatty acid methyl esters. This paper will describe the technology, discuss the results of the LCA study and summarize the advantages this new technology can offer over other processing routes.
Identification of Residues in the CH2/CH3 Domain Interface of IgA Essential for Interaction with the Human Fcα Receptor (FcαR) CD89 (1999)

Cellular receptors for IgA (FcalphaR) mediate important protective functions. An extensive panel of site-directed mutant IgAs was used to identify IgA residues critical for FcalphaR (CD89) binding and triggering. Although a tailpiece-deleted IgA1 was able to bind and trigger CD89, antibodies featuring CH3 domain exchanges between human IgA1 and IgG1 could not, indicating that both domains but not the tailpiece are required for FcalphaR recognition. To further investigate the role of the interdomain region, numerous IgA1s, each with a point substitution in either of two interdomain loops (Leu-257-Gly-259 in Calpha2; Pro-440-Phe-443 in Calpha3), were generated. With only one exception (G259R), substitutions produced either ablation (L257R, P440A, A442R, F443R) or marked reduction (P440R) in CD89 binding and triggering. Further support for involvement of these interdomain loops was provided by interspecies comparisons of IgA. Thus a human IgA1 mutant, LA441-442MN, which mimicked the mouse IgA loop sequence through substitution of two adjacent residues in the Calpha3 loop, was found, like mouse IgA, not to bind CD89. In contrast, bovine IgA1, identical to human IgA1 within these interdomain loops despite numerous differences elsewhere in the Fc region, did bind CD89. We have thus identified motifs in the interdomain region of IgA Fc critical for FcalphaR binding and triggering, significantly enhancing present understanding of the molecular basis of the IgA-FcalphaR interaction.
Organic acid toxicity, tolerance, and production in Escherichia coli biorefining applications (2005)

Abstract Organic acids are valuable platform chemicals for future biorefining applications. Such applications involve the conversion of low-cost renewable resources to platform sugars, which are then converted to platform chemicals by fermentation and further derivatized to large-volume chemicals through conventional catalytic routes. Organic acids are toxic to many of the microorganisms, such as Escherichia coli , proposed to serve as biorefining platform hosts at concentrations well below what is required for economical production. The toxicity is two-fold including not only pH based growth inhibition but also anion-specific effects on metabolism that also affect growth. E. coli maintain viability at very low pH through several different tolerance mechanisms including but not limited to the use of decarboxylation reactions that consume protons, ion transporters that remove protons, increased expression of known stress genes, and changing membrane composition. The focus of this mini-review is on organic acid toxicity and associated tolerance mechanisms as well as several examples of successful organic acid production processes for E. coli .
Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies. (1993)

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. We recently reported linkage of the gene causing FMF (designated "MEF") to two markers on chromosome 16p. To map MEF more precisely, we have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. We also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the high FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location.
Increase of NAD(P)H:quinone reductase by dietary antioxidants: possible role in protection against carcinogenesis and toxicity. (1980)

2(3)-tert-Butyl-4-hydroxyanisole (BHA) is one of several widely used antioxidant food additives that protect against chemical carcinogenesis and toxicity. The present report concerns the enhancement of dicoumarol-inhibited NAD(P)H:quinone reductase [NAD(P)H dehydrogenase (quinone); NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2] activity in mouse tissues in response to dietary administration of BHA. Cytosolic quinone reductase specific activity was increased significantly in 10 of 15 tissues examined from BHA-fed mice. The greatest proportionate increase, to 10 times control levels, was observed in liver. BHA also increased the quinone reductase activities of kidney, lung, and the mucosa of the upper small intestine severalfold. The increases of quinone reductase activities in liver and digestive tissues in response to BHA were comparable to the increases previously observed in glutathione S-transferase (EC 2.5.1.18) and epoxide hydratase (EC 3.3.2.3) activities. Quinones are among the toxic products of oxidative metabolism of aromatic hydrocarbons. NAD(P)H:quinone reductase exhibits broad specificity for structurally diverse hydrophobic quinones and may facilitate the microsomal metabolism of quinones to readily excreted conjugates. The protective effects of BHA appear to be due, at least in part, to the ability of this antioxidant to increase the activities in rodent tissues of several enzymes involved in the nonoxidative metabolism of a wide variety of xenobiotics.