gebhart/patrepeval huggingface dataset:
Desmethyl Macrolides: Synthesis and Evaluation of 4,8,10-Tridesmethyl Telithromycin (2010)

There is an urgent need to discover new drugs to address the pressing problem of antibiotic-resistance. Macrolide antibiotics such as erythromycin (1) are safe, broad-spectrum antibiotics used in the clinic since 1954. Herein we report the synthesis and evaluation of 4,8,10-tridesmethyl telithromycin (3), a novel desmethyl analogue of the 3rd-generation drug telithromycin (2), which is a semisynthetic derivative of 1. Analogue 3 was found to possess antibiotic activity and was superior to telithromycin (2) when tested against resistant strains of S. aureus possessing an A→T mutation at position 2058 (E. coli numbering).
Data Warehousing; Building the Corporate Knowledge Base (1996)

From the Publisher:
Until now, most material focusing on data warehousing has discussed only the data architecture components of the data warehouse. Data Warehousing: Building the Corporate Knowledge Base is one of the first books to offer documented techniques for delving into the complete lifecycle required to successfully deliver a data mart or a data warehouse - including aspects of project management, data architecture, application architecture, load process development, database administration techniques, and more.
Polyfluorenes with Polyphenylene Dendron Side Chains:  Toward Non-Aggregating, Light-Emitting Polymers (2001)

A polyfluorene 12 has been prepared in which bulky polyphenylene dendrimer substituents suppress formation of long wavelength emitting aggregates, thus giving a polymer with pure blue emission. Absorption- and emission spectra and molecular modeling confirm that the bulky dendrimer side chains do not cause extra torsion between the fluorene units. New polyfluorenes with 9,9-diaryl substituents have been prepared to determine the minimum size of substituent necessary for aggregation suppression. An LED using 12 has been demonstrated to produce blue emission with onset voltages below 4 V.
The Effects of Aortic Crossclamping and Resuscitation on Intracranial Pressure, Cerebral Blood Flow, and Cerebral Water Content in a Model of Focal Brain Injury and Hemorrhagic Shock (1990)

Aortic crossclamping (AOXC) is performed frequently in hypotensive trauma patients who may have had a head injury. The effect of AOXC on the injured brain is unknown. We studied the effect of AOXC on mean arterial pressure (MAP), intracranial pressure (ICP), cerebral blood flow (CBF), cerebral perfusion pressure (CPP), and cerebral water content in a porcine model of focal cryogenic brain injury. Four groups of animals were studied: Group I--brain injury only; Group II--brain injury and AOXC; Group III--brain injury with hemorrhage and AOXC; and Group IV--AOXC only. Focal cryogenic grain injury increased the ICP in Groups I-III. Aortic crossclamping increased MAP, CBF, ICP, and CPP after hemorrhage in Group III. Following declamping and resuscitation there were no differences between the groups in any studied variable. Cerebral water content at the site of the focal brain injury was greater than in nonlesioned cortex but there was no significant difference between groups despite a greater positive fluid balance in hemorrhaged animals. AOXC improved perfusion to the injured brain without a significant increase in ICP. Increased MAP induced by AOXC and large fluid resuscitation appeared to have no detrimental effect on ICP, CBF, cerebral water content, or CPP in this model of brain injury.
Recombinant C1b domain of PKCδ triggers meiotic maturation upon microinjection in Xenopus laevis oocytes (2000)

The C1 domains are 50 amino acid sequences present in protein kinase C (PKC) isozymes that are responsible for binding of phorbol esters and the lipid second messenger diacylglycerol (DAG). We found that bacterially expressed C1b domain of PKCdelta induces germinal vesicle breakdown (GVBD) when microinjected into Xenopus laevis oocytes. Injection of the C1b domain of PKCdelta significantly enhanced insulin- but not progesterone-induced maturation. Interestingly, the PKCdelta C1b domain markedly synergized with normal Ras protein to induce oocyte maturation when both proteins were co-injected in oocytes. Our results demonstrate that the purified C1b domain of PKCdelta is sufficient to promote meiotic maturation of X. laevis oocytes probably through activation of components of the insulin/Ras signaling pathway.
The nonuniform distribution of instruction-level and machine parallelism and its effect on performance (1989)

A methodology for quickly estimating machine performance is developed. A first-order estimate is based on the average degree of machine parallelism. A second-order model corrects for the effects of nonuniformities in instruction-level and machine parallelism and is shown to be accurate to within 15% for three widely different machine pipelines: the CRAY-1, the MultiTitan, and a dual-issue superscalar machine.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Programming languages for mobile code (1997)

Sun's announcement of the programming language Java more that anything popularized the notion of mobile code, that is, programs traveling on a heterogeneous network and automatically executing upon arrival at the destination. We describe several classes of mobile code and extract their common characteristics, where security proves to be one of the major concerns. With these characteristics as reference points, we examine six representative languages proposed for mobile code. The conclusion of this study leads to our recommendations for future work, illustrated by examples of ongoing research.
A testable CMOS signal processor for fast Fourier transforms (2003)

The authors present the architecture of a fast Fourier transform processor which has high performance characteristics and an embedded test structure that allows the processor to test itself during normal operation. The properties of separable residue codes have been used for error detection in the arithmetic unit of the processor. Offline error detection which tests for the classic stuck at faults is based on the properties of the dynamic CMOS logic design used. The testing circuitry used in the architecture accounts for only a 20% area overhead and no time ahead, an important saving in a signal-processing environment.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis and expression in Escherichia coli of the gene encoding monocyte-derived neutrophil-activating factor: biological equivalence between natural and recombinant neutrophil-activating factor. (1988)

The neutrophil-activating factor (NAF) purified from the conditioned medium of lipopolysaccharide-stimulated human monocytes was sequenced and found to consist of 72 amino acids: SAKELRCQCIKTYSKPFHPKFIKELRVIESGPHCANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRA ENS. Purified preparations of natural NAF contained, in addition to this main form, minor amounts of three amino-terminal variants with 77 (+AVLPR), 70, and 69 residues. A gene coding for the 72-amino acid NAF was synthesized, cloned, and expressed in Escherichia coli. Western (immunologic) blot analysis of crude bacterial extracts, with an antiserum raised against natural NAF, revealed a single band that comigrated with natural NAF. Recombinant NAF purified to homogeneity had identical amino- and carboxyl-terminal sequences to the 72-amino acid natural NAF. Recombinant NAF was tested on human neutrophils and had the same activity and potency as natural NAF in inducing chemotaxis, rapidly increasing cytosolic free Ca2+, activating the respiratory burst, and releasing specific and azurophilic granular contents.
Proteinase‐resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity (1991)

Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases.
Effects of policosanols and phytosterols on lipid levels and cholesterol biosynthesis in hamsters (2003)

The current study was carried out to examine the effects of policosanols and phytosterols, alone and in combination, on lipid profiles, cholesterol biosynthesis, and tissue histopathological changes in hamsters. Fifty male Golden Syrian hamsters, weighing 100 to 120 g, were fed a regular rodent chow for 2 wk before being randomly assigned into 5 groups of 10 animals each fed semisynthetic diets for 4 wk. Group 1 was given a control diet that contained 0.25% cholesterol and 5% fat with a PUFA to saturated FA ratio of 0.4. Groups 2 to 5 were fed the control diet and given Octa-6 [a policosanol mixture from sugar cane wax, 25 mg/kg body weight (BW)], Ricewax (a policosanol mixture from rice wax with 50% being converted to the corresponding acids, 50 mg/kg BW), phytosterols (Cholestatin; 1,000 mg/kg BW), and Ricewax (50 mg/kg BW) plus phytosterols (1,000 mg/kg BW), respectively. The results showed that there was no difference between Octa-6 and Ricewax treatments in any of the lipid parameters measured, and both had similar levels of triglyceride (TG), total cholesterol (T-C), and HDL cholesterol (HDL-C) as the control. Octa-6 but not Ricewax increased (P = 0.03) non-HDL-C as compared with the control. Phytosterols reduced T-C (P < 0.0003) and HDL-C (P < 0.004) without a significant effect on TG and non-HDL-C as compared to the control. Ricewax plus phytosterols had effects similar to those with phytosterols alone. Free cholesterol synthetic rates were not different among the treatments. Policosanols or phytosterols did not show any toxic effects in liver, heart, brain, or kidney. Results suggest that, although phytosterols reduce T-C and HDL-C levels, policosanols have no significant favorable effect in changing lipid levels in hamsters.
The Role of Thiols in Liver Ischemia-Reperfusion Injury (2006)

Thiol-containing compounds have an essential role in many biochemical reactions due to their ability to be easily oxidised and then quickly regenerated. Main representatives are glutathione, lipoic acid and thioredoxin which are synthesised de novo in mammalian cells. N-acetylcysteine and Bucillamine are synthetic thiols which have been administered in experimental and clinical studies for treatment of conditions associated with oxidative stress. Ischemia and reperfusion (I/R) injury is characterised by significant oxidative stress, characteristic changes in the antioxidant system and organ injury leading to significant morbidity and mortality. I/R occurs in a variety of clinical settings such as liver resection, organ transplantation, haemorrhagic shock with fluid resuscitation, heart surgery, myocardial infarction followed by reperfusion and laparoscopic surgery. In these circumstances, the administration of antioxidant agents such as thiols, could provide protection from the harmful effects of I/R injury. However, the ability of thiol compounds to reduce free radicals is associated with the formation of thiyl radicals and the rate and efficiency of removal of thiyl radicals has a critical effect on antioxidant or prooxidant actions of thiols in the cells. The aim of this review is to present the mechanisms by which thiols act as antioxidants and signalling molecules and the experimental and clinical evidence regarding their role in I/R injury with a particular emphasis on liver I/R. The current evidence suggests that thiols ameliorate I/R injury and that their clinical significance should be further evaluated in large scale randomised clinical trials.
Amiodarone Inhibits Thyroidal Iodide Transport in Vitro by a Cyclic Adenosine 5′-Monophosphate- and Iodine-Independent Mechanism (2006)

Thyroid side effects are common in patients treated for cardiac arrhythmias with amiodarone (AM). A major disturbance is inhibited thyroidal radioiodine uptake in AM-induced thyrotoxicosis, which makes 131I therapy ineffective. On the other hand, failure to escape from the Wolff-Chaikoff effect by down-regulation of the sodium/iodide symporter (NIS) is proposed to explain AM-induced hypothyroidism. However, previously no experimental studies on the possible mechanisms have been conducted. We therefore investigated the early effects of AM on thyroidal iodide transport using bicameral chamber cultures of primary pig thyrocytes that reproduce the three tissue compartments (epithelium, lumen, and extrafollicular space) of the gland. AM dose-dependently (1-50 microm) inhibited the TSH-stimulated transepithelial (basal to apical) transport of 125I- by up to 90%. The inhibitory effect was noticed already after 8 h and was further pronounced after 1-4 d, depending on the AM concentration. The intracellularly accumulated 125I- was reduced by perchlorate but not AM, and quantitative real-time RT-PCR revealed no change in the NIS expression in AM-treated cells. Blocking of cAMP degradation with 3-isobutyl-1-methylxanthine or withdrawal of AM reversed AM-induced changes in electrolyte transport but were unable to recover the suppressed 125I- transport. The iodine-free AM analog dronedarone also inhibited 125I- transport to the same extent as AM. The findings indicate that AM blocks thyroidal iodide uptake by reducing the iodide permeability of the apical plasma membrane of the thyroid epithelial cells. The effect is iodine independent and long-lasting and does not involve impaired function of NIS or the TSH receptor/cAMP signaling pathway.
Expression of CD46, CD55, and CD59 on renal tumor cell lines and their role in preventing complement-mediated tumor cell lysis. (1996)

Nucleated cells are protected from complement-mediated injury by the expression of membrane-bound regulators of complement activation (mRCA) CD46, CD55, and CD59. Increased expression of these mRCA may be a mechanism by which tumor cells protect themselves from complement-mediated injury and prevent an inflammatory response. In the present study, we have investigated whether human renal tumor cell lines and cultured proximal tubular epithelial cells express CD46, CD55, and CD59 and whether these mRCA influence complement-mediated lysis of these cells. The expression of CD46, CD55, and CD59 was measured by flow cytometry. To determine the effect of mRCA on lysis, tumor cells were opsonized with complement activating anti-HLA class l mAb. Lysis was measured in the presence or absence of anti-CD46, anti-CD55 or anti-CD59 mAb and serum as a source of complement, using a 51Cr release assay. Flow cytometric analysis revealed that renal tumor cell lines and proximal tubular epithelial cells all express CD46, CD55, and CD59. Lysis of renal tumor cell lines in the presence of rabbit serum depended on the number of HLA class I molecules expressed by the tumor cells. Using human serum, complement-mediated lysis was decreased by at least one-third as compared with rabbit serum. The susceptibility of renal tumor cells for complement-mediated lysis could be increased up to the level observed with rabbit serum by inhibiting the function of CD59. Inhibition of the function of CD46 or CD55 with mAb directed against these mRCA had no substantial effect on lysis. We conclude from this work that renal tumor cells and proximal tubular epithelial cells express CD46, CD55, and CD59. Of these mRCA, CD59 is most efficient in preventing complement-mediated lysis of these cells. Expression of mRCA on tumor cells may influence the effectiveness of immunotherapy with tumor-associated mAb.
Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis – Potential implications for sports drug testing programs (2016)

Focusing on skeletal muscle and mitochondrial biogenesis, numerous substances exhibiting agonistic or antagonistic actions on different cellular 'control centers' resulting in increased skeletal muscle mass, enhanced performance (as determined with laboratory animal models), and/or elevated amounts of mitochondria have been described. Substances of interest include agonists for REV-ERBα (e.g. SR9009, SR9011, SR10067, GSK4112), sirtuin 1 (e.g. SRT1720, SRT2104), adenosine monophosphate-activated protein kinase (AMPK, e.g. AICAR), peroxisome proliferator-activated receptor (PPAR)δ (e.g. GW1516, GW0742, L165041), and inhibitory/antagonistic agents targeting the methionine-folate cycle (MOTS-c), the general control non-derepressible 5 (GCN5) acetyl transferase (e.g. CPTH2, MB-3), myostatin (e.g. MYO-029), the myostatin receptor (bimagrumab), and myostatin receptor ligands (e.g. sotatercept, ACE-031). In addition, potentially relevant drug targets were identified, e.g. with the sarcoplasmic transmembrane peptide myoregulin and the nuclear receptor corepressor 1 (NCOR-1). The antagonism of these has shown to result in substantially enhanced physical performance in animals, necessitating the monitoring of strategies such as RNA interference regarding these substances. Most drug candidates are of lower molecular mass and comprise non-natural compositions, facts which suggest approaches for their qualitative identification in doping control samples by mass spectrometry. Electrospray ionization/collision-induced dissociation mass spectra of representatives of the aforementioned substances and selected in vitro derived phase-I metabolites support this assumption, and test methods for a subset of these have been recently established. Expanding the knowledge on analytical data will further facilitate the identification of such analytes and related compounds in confiscated material as well as sports drug testing specimens.
RESTRICTION OF HERPES SIMPLEX VIRUS BY MACROPHAGES (1971)

Macrophages restrict herpes simplex virus replication and can prevent the development of herpetic disease in mice. In an attempt to define the nature of this restriction, an analysis of virus-specified macromolecular syntheses in infected macrophages was undertaken. The significant results were the following: All cells were killed, but the infection was considered to be abortive since the level of infectious virus in macrophage cultures dropped steadily to a level beyond detection by 25 hr after infection. This restriction appeared to be specific for macrophages; the virus replicated efficiently in other mouse cells. DNA with a density characteristic for herpes simplex virus DNA was extracted from infected cultures, and the proportion of macrophages synthesizing DNA increased from less than 1% to greater than 50% by 6 hr after infection. Studies employing polyacrylamide gel electrophoresis indicated that the major viral-specific proteins were induced in macrophage cultures. In addition, all cells showing cytopathic changes characteristic of herpes virus infection also contained viral antigens which could be detected by fluorescent antibody techniques and, by 15 hr after infection, most contained nascent capsids lacking central dense cores. It is suggested that an error in DNA metabolism may be the primary cause of restriction.
Light-stable rhodopsin. I. A rhodopsin analog reconstituted with a nonisomerizable 11-cis retinal derivative. (1992)

With the aim of preparing a light-stable rhodopsin-like pigment, an analog, II, of 11-cis retinal was synthesized in which isomerization of the C11-C12 cis-double bond is blocked by a cyclohexene ring built around the C10 to C13-methyl. The analog II formed a rhodopsin-like pigment (rhodopsin-II) with opsin expressed in COS-1 cells and with opsin from rod outer segments. The rate of rhodopsin-II formation from II and opsin was approximately 10 times slower than that of rhodopsin from 11-cis retinal and opsin. After solubilization in dodecyl maltoside and immunoaffinity purification, rhodopsin-II displayed an absorbance ratio (A280nm/A512nm) of 1.6, virtually identical with that of rhodopsin. Acid denaturation of rhodopsin-II formed a chromophore with lambda max, 452 nm, characteristic of protonated retinyl Schiff base. The ground state properties of rhodopsin-II were similar to those of rhodopsin in extinction coefficient (41,200 M-1 cm-1) and opsin-shift (2600 cm-1). Rhodopsin-II was stable to hydroxylamine in the dark, while light-dependent bleaching by hydroxylamine was slowed by approximately 2 orders of magnitude relative to rhodopsin. Illumination of rhodopsin-II for 10 s caused approximately 3 nm blue-shift and 3% loss of visible absorbance. Prolonged illumination caused a maximal blue-shift up to approximately 20 nm and approximately 40% loss of visible absorbance. An apparent photochemical steady state was reached after 12 min of illumination. Subsequent acid denaturation indicated that the retinyl Schiff base linkage was intact. A red-shift (approximately 12 nm) in lambda max and a 45% recovery of visible absorbance was observed after returning the 12-min illuminated pigment to darkness. Rhodopsin-II showed marginal light-dependent transducin activation and phosphorylation by rhodopsin kinase.
Recent advances in magnetic nanoparticle-based multi-modal imaging (2015)

Magnetic nanoparticles have been extensively explored as a versatile platform for magnetic resonance imaging (MRI) contrast agents due to their strong contrast enhancement effects together with the platform capability for multiple imaging modalities. In this tutorial review, we focus on recent progress in the use of magnetic nanoparticles for MRI contrast agents and multi-mode imaging agents such as T1-T2 MRI, MRI-optical, and MRI-radioisotopes. This review also highlights emerging magnetic imaging techniques such as magnetic particle imaging (MPI), magneto-motive ultrasound imaging (MMUS), and magneto-photoacoustic imaging (MPA).