gebhart/patrepeval huggingface dataset:
Immobilization of acrylamide-modified oligonucleotides by co-polymerization (1999)

A flexible chemistry for solid phase attachment of oligonucleotides is described. Oligonucleotides bearing 5'-terminal acrylamide modifications efficiently co-polymerize with acrylamide monomers to form thermally stable DNA-containing polyacrylamide co-polymers. Co-polymerization attachment is specific for the terminal acrylamide group. Stable probe-containing layers are easily fabricated on supports bearing exposed acrylic groups, including plastic microtiter plates and silanized glass. Attachment can be accomplished using standard polyacrylamide gel recipes and polymerization techniques. Supports having a high surface density of hybridizable oligonucleotide (approximately 200 fmol/mm2) can be produced.
Dendritic Cells Undergo Rapid Apoptosis In Vitro During Antigen-Specific Interaction with CD4+ T Cells (1999)

The terminal fate of dendritic cells (DC) remains relatively uncertain. In this study, we tested the hypothesis that DC undergo apoptosis after Ag-specific interaction with T cells. When splenic DC isolated from BALB/c mice were cocultured with HDK-1 T cells (a keyhole limpet hemocyanin (KLH)-specific CD4+ Th1 clone) in the presence of KLH, they showed conspicuous cell death as measured by propidium iodide (PI) uptake and chromatin condensation, whereas they remained relatively intact when incubated with either T cells or KLH alone. Likewise, the long term DC line XS52, which was established from BALB/c mouse epidermis, also died rapidly (within 2 h), and they exhibited characteristic DNA laddering when cocultured with HDK-1 T cells in the presence of KLH. RT-PCR and FACS analyses revealed the expression of CD95 (Fas) by XS52 DC and of CD95 ligand (CD95L) (Fas ligand) by activated HDK-1 T cells, suggesting a functional role for these molecules. In fact, anti-CD95L mAb inhibited partially (50%) T cell-mediated XS52 cell death, and coupling of surface CD95 with anti-CD95 mAb triggered significant XS52 cell death, but only in the presence of cycloheximide. Thus, ligation of CD95 (on DC) with CD95L (on T cells) is one, but not the only, mechanism by which T cells induce DC death. Finally, DC isolated from the CD95-deficient mice were found to be significantly more efficient than DC from control mice in their capacity to induce delayed type hypersensitivity responses in vivo. We propose that T cell-induced DC apoptosis serves as a unique down-regulatory mechanism that prevents the interminable activation of T cells by Ag-bearing DC.
Fermentation of d -Xylose and l -Arabinose to Ethanol by Erwinia chrysanthemi (1987)

Erwinia spp. are gram-negative facultative anaerobes within the family Enterobacteriacae which possess several desirable traits for the conversion of pentose sugars to ethanol, such as the ability to ferment a broad range of carbohydrates and the ease with which they can be genetically modified. Twenty-eight strains of Erwinia carotovora and E. chrysanthemi were screened for the ability to ferment d-xylose to ethanol. E. chrysanthemi B374 was chosen for further study on the basis of its superior (4%) ethanol tolerance. We have characterized the fermentation of d-xylose and l-arabinose by the wild type and mutants which bear plasmids containing the pyruvate decarboxylase gene from Zymomonas mobilis. Expression of the gene markedly increased the yields of ethanol (from 0.7 up to 1.45 mol/mol of xylose) and decreased the yields of formate, acetate, and lactate. However, the cells with pyruvate decarboxylase grew only one-fourth as fast as the wild type and tolerated only 2% ethanol. Alcohol tolerance was stimulated by the addition of yeast extract to the growth medium. Xylose catabolism was characterized by a high saturation constant K(s) (4.5 mM).
Effects of complete renal denervation and selective afferent renal denervation on the hypertension induced by intrarenal norepinephrine infusion in conscious rats (1989)

To test the hypothesis that continuous intrarenal norepinephrine (NE) infusions produce hypertension via activation of afferent renal nerves (ARN), rats were subjected to complete renal denervation (RN-x), selective renal deafferentation (ARN-x) or sham surgery, prior to infusion of NE. In the pre-infusion period, mean arterial pressure (MAP) was significantly lower in RN-x than in ARN-x or sham-operated rats. Plasma renin concentration (PRC) was significantly reduced following ARN-x, but not RN-x. During 5-day intrarenal infusions of 4, 12 or 36 micrograms NE/kg per h, MAP rose to similar levels in RN-x and sham-RN-x rats. However, RN-x rats exhibited significantly elevated PRC levels, suggesting that denervation supersensitivity masked the possible effects of RN-x. In sham-RN-x rats, MAP increased significantly more during intrarenal infusion of 12 micrograms NE/kg per h than during intravenous infusion of the same amount. In ARN-x rats, MAP rose to a similar degree during intravenous and intrarenal infusions. The pressor responses in the ARN-x rats, however, were not significantly smaller at any point than those in intact rats. PRC rose to comparable levels in ARN-x and intact rats. Thus, in normotensive rats, efferent renal nerves (ERN) but not ARN are of functional significance in maintaining basal blood pressure. ARN may be involved in the control of renin release. Since neither RN-x nor ARN-x attenuated the development of hypertension, renal nerves are not necessary for the full expression of hypertension in this model.
Regiospecific synthesis of cyclopentane analogs of (2′- and 3′-deoxy-threo-pentofuranosyl)-uracil and -2-thiouracil nucleosides (1985)

Aminohydroxycyclopentanemethanols are important precursors for the synthesis of cyclopentane analogs of purine and pyrimidine nucleosides. The regiospecific synthesis of two new aminohydroxycyclopentanemethanols, 17 and 22, is described. In these syntheses the desired configuration in the cyclopentane ring is obtained by opening the cis-acetoxy-1,3-cyclopentanedicarboxylic acid anhydride 3 with either ammonia or methanol. The attack by each nucleophile occurs at the carbonyl carbon farthest away from the acetoxy group to give a carbamoyl or an ester function at this position. Since the ester function is destined to become the hydroxymethyl substituent and the carbamoyl function the amino substituent, the type of nucleophile used to open the anhydride determines whether the 2-deoxy or the 3-deoxy isomer is obtained. Coupling of the aminohydroxycyclopentanemethanols with 3-ethoxypropenoyl isocyanate followed by cyclization of the acyl ureas in 2 N H 2 SO 4 gave two new cyclopentane analogs of uracil nucleosides. Coupling of the aminohydroxycyclopentanemethanols with 3-ethoxypropenoyl isothiocyanate followed by cyclization of the acyl thioureas in 15 N aqueous ammonia gave two new cyclopentane analogs of 2-thiouracil nucleosides.
Electronic structure of 3d-transition-metal compounds by analysis of the 2pcore-level photoemission spectra (1992)

The electronic structures of a wide range of transition-metal compounds, including Cu, Ni, Co, Fe, and Mn oxides and sulfides, with metal valences ranging from 2+ to 4+, have been investigated by a cluster-type configuration-interaction analysis of the core-level 2p x-ray photoemission spectra. We show that by including the d-d exchange interaction (retaining only diagonal terms) and an anisotropic metal-ligand hybridization in the model, these spectra can be well reproduced, and so can be used to deduce quantitatively values for the ligand-to-metal charge-transfer energy \ensuremath{\Delta}, the on-site d-d Coulomb repulsion energy U, and the metal-ligand transfer integrals T. Systematics for \ensuremath{\Delta} and U are generally consistent with those found from previous valence-band studies and follow expected chemical trends. By using values of \ensuremath{\Delta} and U found from this model, we show that most of the transition-metal compounds studied in this work can be classified in the charge-transfer regime of the Zaanen-Sawatzky-Allen diagram. A few exceptions to these systematics have been found. Small U values found for pyrite-type ${\mathrm{CoS}}_{2}$ and ${\mathrm{FeS}}_{2}$ and large T values for Mn perovskite oxides, as well as the neglect of other mechanisms such as exciton satellites, may indicate a limitation of the local-cluster model.
Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants. (1996)

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.
SUGAR-DEPENDENT1 Encodes a Patatin Domain Triacylglycerol Lipase That Initiates Storage Oil Breakdown in Germinating Arabidopsis Seeds (2006)

Triacylglycerol hydrolysis (lipolysis) plays a pivotal role in the life cycle of many plants by providing the carbon skeletons and energy that drive postgerminative growth. Despite the physiological importance of this process, the molecular mechanism is unknown. Here, a genetic screen has been used to identify Arabidopsis thaliana mutants that exhibit a postgerminative growth arrest phenotype, which can be rescued by providing sugar. Seventeen sugar-dependent (sdp) mutants were isolated, and six represent new loci. Triacylglycerol hydrolase assays showed that sdp1, sdp2, and sdp3 seedlings are deficient specifically in the lipase activity that is associated with purified oil bodies. Map-based cloning of SDP1 revealed that it encodes a protein with a patatin-like acyl-hydrolase domain. SDP1 shares this domain with yeast triacylglycerol lipase 3 and human adipose triglyceride lipase. In vitro assays confirmed that recombinant SDP1 hydrolyzes triacylglycerols and diacylglycerols but not monoacylglycerols, phospholipids, galactolipids, or cholesterol esters. SDP1 is expressed predominantly in developing seeds, and a SDP1-green fluorescent protein fusion was shown to associate with the oil body surface in vivo. These data shed light on the mechanism of lipolysis in plants and establish that a central component is evolutionarily conserved among eukaryotes.
Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent (1984)

Chelation of the rare-earth element gadolinium (Gd) with diethylenetriaminepentaacetic acid (DTPA) results in a strongly paramagnetic, stable complex that is well tolerated in animals. The strongly paramagnetic gadolinium complex reduces hydrogen-proton relaxation times even in low concentrations (less than 0.01 mmol/L). The pharmacokinetic behavior of intravenously delivered Gd-DTPA is similar to the well known iodinated contrast agents used in urography and angiography; excretion is predominantly through the kidneys with greater than 90% recovery in 24 hr. The intravenous LD50 of the meglumine salt of Gd-DTPA is 10 mmol/kg for the rat; in vivo there is no evidence of dissociation of the gadolinium ion from the DTPA ligand. The combination of strong proton relaxation, in-vivo stability, rapid urinary excretion, and high tolerance favors the further development and the potential clinical application of gadolinium-DTPA as a contrast enhancer in magnetic resonance imaging.
Once-daily dosing of aminoglycosides: review and recommendations for clinical practice (1997)

The use of higher-dose, extended interval (i.e., once-daily) aminoglycoside regimens to optimize bacterial killing is justified by a pharmacodynamic principle of aminoglycosides, namely concentration-dependent killing, and by the partial attribution of the toxicity of aminoglycosides to prolonged serum concentrations. Numerous in-vitro and animal studies have supported using once-daily aminoglycoside dosing. Clinical studies show at least equal effectiveness and no greater toxicity when compared with traditional regimens. A dose of 5-7 mg/kg of gentamicin, tobramycin, or netilmicin, with at least a 24 h dosing interval should be employed and a similar regimen can be applied to amikacin dosing. As yet, there are some patient populations that have not been adequately studied to determine whether or not oncedaily aminoglycoside dosing would be a better choice than traditional dosing regimens.
Betahistine for Meniere’s disease (2016)

Betahistine is ineffective, patients urgently need better alternatives

The publication of a very well constructed randomised controlled trial1 of betahistine (Serc) for Meniere’s disease underlines the lack of evidence for the efficacy of this drug at both low and high doses. What does this mean for current and future users?

Meniere’s disease is one of the most puzzling inner ear syndromes. It is typically described with a collection of symptoms, which might not occur all at once in the same person. These include tinnitus, vertigo, sensorineural hearing loss, and aural fullness. Currently, we don’t have a precise idea of aetiology, despite many efforts to indentify underlying causes. Common sensory or pathophysiological elements have been observed—such as endolymphatic hydrops (a distension of the membranous labyrinth2)—and some aetiological theories have been proposed, none of which has been able to inform a one-for-all treatment.

The general approach to treatment is influenced by the severity of the symptoms, by the professional and personal views of the treating specialist, and by …
Synthesis and Structural Characterization of Double Metal Cyanides of Iron and Zinc:  Catalyst Precursors for the Copolymerization of Carbon Dioxide and Epoxides (2003)

Several synthetic approaches for the preparation of double metal cyanide (DMC) derivatives of iron(II) and zinc(II) are described. These include (1) metathesis reactions of ZnCl(2) or ZnI(2) with KCpFe(CN)(2)CO in aqueous solution, (2) reactions of KCpFe(CN)(2)CO and its phosphine-substituted analogues with Zn(CH(3)CN)(4)(BF(4))(2) and subsequent displacement of acetonitrile at the zinc centers by the addition of a neutral (phosphine) or anionic (phenoxide) ligand, and (3) reactions of the protonated HCpFe(CN)(2)(phosphine) complexes with Zn(N(SiMe(3))(2))(2), followed by the addition of phenols. All structures are based on a diamond-shaped planar arrangement of the Fe(2)(CN)(4)Zn(2) core with various appended ligands at the metal sites. Although attempts to replace the iodide ligands in [CpFe(mu-CN)(2)PPh(3)ZnI(THF)](2) with acetate using silver acetate failed, two novel cationic mixed-metal cyanide salts based on the [CpFe(PPh(3))(mu-CN)(2)Zn(NC(5)H(5))](2)(2+) framework were isolated from pyridine solution and their structures were defined by X-ray crystallography. The anionic ligand bound to zinc in these derivatives, which serve as an anionic polymerization initiator, was shown to be central to the catalytic copolymerization reaction of CO(2)/epoxide to provide polycarbonates and cyclic carbonates. The structurally stabilized phosphine-strapped complexes [CpFe(mu-CN)(2)Zn(X)THF](2)(mu-dppp), where X = I or phenolate, were shown to be thermally stable under the conditions (80 degrees C) of the copolymerization reaction by in situ infrared spectroscopy. Both of these derivatives were proposed to serve as mimics for the heterogeneous DMC catalysts in the patent literature, with the derivative where the initiator is a phenolate being more active for the production of polycarbonates.
Transthoracic Electrical Impedance as a Guide to Intravascular Overload (1971)

Electrical impedance methods have been used to document the accumulation of fluid in living tissues. Change in transthoracic electrical impedance was studied in dogs during deliberate overinfusion with albumin in normal saline solution. Fall in transthoracic impedance was regularly observed with acute intravascular volume overload. Change in transthoracic impedance was accompanied by elevated cardiac output, fall in peripheral resistance and peripheral and pulmonary arteriovenous shunting. Pulmonary interstitial edema occurred in all animals. Impedance changes occur as the result of increased conductivity due to decreased intrapulmonary aeration (atelectasis) or to increased intrathoracic fluid volume. Relative changes in electrical impedance appear to be as sensitive as central venous pressure in the detection of intrathoracic volume changes.
Van de werkvloer (2006)

In Martini Ziekenhuis (Groningen) draait het project ‘vmbo-Carrousel’ inmiddels een jaar. De eerste ervaringen zijn positief. ‘De Carrousel geeft vmbo-leerlingen spelenderwijs inzicht in het reilen en zeilen van het ziekenhuis’, aldus Karin Voorintholt, opleidingsfunctionaris bij het ziekenhuis.
Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1 (2016)

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small-molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure- and ligand-based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4-aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure-activity relationships of these inhibitor series.
The Viterbi algorithm and Markov noise memory (2000)

This work designs sequence detectors for channels with intersymbol interference (ISI) and correlated (and/or signal-dependent) noise. We describe three major contributions. (i) First, by modeling the noise as a finite-order Markov process, we derive the optimal maximum-likelihood sequence detector (MLSD) and the optimal maximum a posteriori (MAP) sequence detector extending to the correlated noise case the Viterbi algorithm. We show that, when the signal-dependent noise is conditionally Gauss-Markov, the branch metrics in the MLSD are computed from the conditional second-order noise statistics. We evaluate the branch metrics using a bank of finite impulse response (FIR) filters. (ii) Second, we characterize the error performance of the MLSD and MAP sequence detector. The error analysis of these detectors is complicated by the correlation asymmetry of the channel noise. We derive upper and lower bounds and computationally efficient approximations to these bounds based on the banded structure of the inverses of Gauss-Markov covariance matrices. An experimental study shows the tightness of these bounds. (iii) Finally, we derive several classes of suboptimal sequence detectors, and demonstrate how these and others available in the literature relate to the MLSD. We compare their error rate performance and their relative computational complexity, and show how the structure of the MLSD and the performance evaluation guide us in choosing a best compromise between several types of suboptimal sequence detectors.
Characterization of Reference Artemia III for Marine Toxicological Studies (1991)

ASTM Practice for Using Brine Shrimp Nauplii as Food for Test Animals in Aquatic Toxicology Tests (E 1203) suggests use of Reference Artemia as a reference standard for evaluating other batches of brine shrimp as food for organisms used in toxicology. In 1988, the U.S. EPA was able to procure a 200-kg quantity of presumed high-quality, small-sized Artemia cysts that had been homogeneously mixed and packaged for long-term storage. These cysts and hatched nauplii have now been characterized in terms of fatty acid profile, toxicant residues, biometrics, and ability to support good survival and growth of saltwater fish and survival and reproduction of saltwater mysids. These cysts have been approved for use as reference cysts and have been designated RAC III. The fatty acid profile of the RAC III includes a 20:5w3 level greater than 7%, which is in excess of the 5% minimum level recommended for marine fish and crustacean larvae. The size of the newly hatched nauplii is &amp;lt;430 μm, which is in the low end of the normal size range (420 to 520 μm) for Artemia nauplii from various strains. Thus they should be relatively easily ingested by marine fish larvae. Analyses of RAC III for metals, organophosphorus pesticides, chlorinated pesticides, and PCBs indicate no problems with toxicant residues. RAC III nauplii were evaluated as a food for marine fish and crustaceans in comparison to RAC II nauplii and a known poor-quality Artemia. There were no statistical differences in survival and growth of sheepshead minnows (Cyprinodon variegatus) and inland silversides (Menidia beryllina) raised on RAC II and RAC III. Survival and reproduction of mysids (Mysidopsis bahia) raised for 25 days on RAC III were comparable to RAC II-raised mysids. The availability of RAC III to U.S. marine toxicologists will make it easier for them to comply with ASTM E 1203 and therefore help to assure the quality of the toxicological data that they generate.
Plasma and Kidney Angiotensin Peptides: Importance of the Aminopeptidase A/Angiotensin III Axis (2015)

BACKGROUND The renin-angiotensin system is a complex regulatory hormonal network with a main biological peptide and therapeutic target, angiotensin (Ang) II (1–8). There are other potentially important Ang peptides that have not been well evaluated. METHODS Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was used for concurrent evaluation of multiple Angs downstream of Ang I (1–10) and Ang II (1–8) in kidney and plasma from wild-type (WT) mice. Angiotensin converting enzyme 2 knockout (ACE2KO) was also used as a way to examine the Angs profile in the absence of ACE2, an enzyme that cleaves both Ang I (1–10) and Ang II (1–8). RESULTS In plasma from both WT and ACE2KO, levels of Ang I (1–10), Ang III (2–8), and Ang (2–10) were the highest of all the renin-angiotensin system (RAS) peptides. The latter two peptides are products of aminopeptidase A cleavage of Ang II (1–8) and Ang I (1–10), respectively. In contrast, plasma levels of Ang II (1–8), and Ang (1–7), the product of Ang II (1–8) cleavage by ACE2, were low. In kidney from both WT and ACE2KO, Ang II (1–8) levels were high as compared to plasma levels. In the ACE2KO mice, a significant increase in either Ang II (1–8) or a decrease in Ang (1–7) was not observed in plasma or in the kidney. CONCLUSION RAS-focused peptidomic approach revealed major differences in Ang peptides between mouse plasma and kidney. These Ang peptide profiles show the dominance of the aminopeptidase A/Ang (2–10) and aminopeptidase A/Ang III (2–8) pathways in the metabolism of Ang I (1–10) and Ang II (1–8) over the ACE2/Ang (1–7) axis. Ang III (2–8) and other peptides formed from aminopeptidase A cleavage may be important therapeutic RAS targets.