gebhart/patrepeval huggingface dataset:
A General Strategy for Stereoselective Glycosylations (2005)

The principal challenge that the synthesis of oligosaccharides of biological importance presents is the development of a general approach for the stereoselective introduction of a glycosidic linkage. It is shown here that a (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety at C-2 of a glycosyl donor can perform neighboring group participation to give a quasi-stable anomeric sulfonium ion. Due to steric and electronic factors, the sulfonium ion is formed as a trans-decalin ring system. Displacement of the sulfonium ion by a hydroxyl leads to the stereoselective formation of alpha-glycosides. NMR experiments were employed to show convincingly the presence of the beta-linked sulfonium ion intermediate. The (1S)-phenyl-2-(phenylsulfanyl)ethyl moiety could be introduced by reaction of a sugar alcohol with acetic acid (1S)-phenyl-2-(phenylsulfanyl)ethyl ester in the presence of BF(3)-OEt(2). Furthermore, it could be removed by conversion into acetate by treatment with BF(3)-OEt(2) in acetic anhydride. The introduction as well as the cleavage reaction proceeds through the formation of an intermediate episulfonium ion. The use of the new methodology in combination with traditional neighboring group participation by esters to introduce beta-glycosides makes it possible, for the first time, to synthesize a wide variety of oligosaccharides by routine procedures. The latter was demonstrated by the synthesis of the Galili trisaccharide, which has been identified as an epitope that can trigger acute rejections in xeno-transplantations, by the one-pot two-step glycosylation sequence.
Composite human VKgenes and a model of their evolution (1984)

A phage library and two cosmid libraries were screened for human VK genes. Two recombinant phage and four cosmid clones were analysed in detail by restriction mapping and sequencing. Each one contained a single VKI sequence. Two of these six sequences are potentially functional VK genes and four are pseudogenes. Two pseudogenes derived from different genomic DNAs are highly homologous and are therefore either allelic variants or the products of a recent duplication event. Comparisons of our sequences with all fully determined human VKI amino acid and DNA sequences reveal identical segments which at first sight appear like minigenes. But these segments do not coincide with the subregions and some of the segments include both, framework and complementarity determining regions (FR, CDR, ref. 2). The findings may be explained by an evolutionary model generating composite genes by gene conversion and selection.
A method for speed optimized partial product reduction and generation of fast parallel multipliers using an algorithmic approach (1996)

This paper presents a method and an algorithm for generation of a parallel multiplier, which is optimized for speed. This method is applicable to any multiplier size and adaptable to any technology for which speed parameters are known. Most importantly, it is easy to incorporate this method in silicon compilation or logic synthesis tools. The parallel multiplier produced by the proposed method outperforms other schemes used for comparison in our experiment. It uses the minimal number of cells in the partial product reduction tree. These findings are tested on design examples simulated in 1 /spl mu/ CMOS ASIC technology.
Repair of Bone Defects Treated with Autogenous Bone Graft and Low-Power Laser (2006)

Because bone healing at the graft site is similar to a fracture repair, the purpose of the present study was to evaluate the effects of low-power laser irradiation on the repair of rat skull defects treated with autogenous bone graft. A defect measuring 3 mm in diameter was produced in the left parietal bone and filled with an autogenous bone graft obtained from the right parietal bone. The animals were divided into 3 groups of 20 rats each: nonirradiated control, irradiated with 5.1 J/cm, and irradiated with 10.2 J/cm. The laser (2.4 mW, 735 nm, 3.4 x 10 W/cm, 3-mm spot size) was applied three times per week for 4 weeks. Greater volume of newly formed bone was observed in the irradiated group with 10.2 J/cm. In both irradiated groups, a greater volume of newly formed bone occurred only in the first 2 weeks. The results demonstrated that laser irradiation at the grafted site stimulated osteogenesis during the initial stages of the healing process in a skull defect of the rat and that this effect was dose dependent.
Articular cartilage repair: procedures versus products (2007)

This review discusses the current perspectives and practices regarding the treatment of articular cartilage injury. Specifically, the authors have delineated and examined articular cartilage repair techniques as either surgical procedures or manufactured products. Although both methodologies are used to treat articular cartilage injury, there are obvious advantages and disadvantages to the application of both, with the literature providing few recommendations on the most suitable regimen for the patient and surgeon. In recent times, cell-based tissue engineering products, predominantly autologous chondrocyte implantation, have been the subject of much research and have become clinically popular. Herein, we review the most used procedures and products in cartilage repair, compare and contrast their outcomes, and evaluate the issues that must be overcome in order to improve patient efficacy in the future.
A Tightly Associated Serine/Threonine Protein Kinase Regulates Phosphoinositide 3-Kinase Activity (1993)

We identified a serine/threonine protein kinase that is associated with and phosphorylates phosphoinositide 3-kinase (PtdIns 3-kinase). The serine kinase phosphorylates both the 85- and 110-kDa subunits of PtdIns 3-kinase and purifies with it from rat liver and immunoprecipitates with antibodies raised to the 85-kDa subunit. Tryptic phosphopeptide maps indicate that p85 from polyomavirus middle T-transformed cells is phosphorylated in vivo at three sites phosphorylated in vitro by the associated serine kinase. The 85-kDa subunit of PtdIns 3-kinase is phosphorylated in vitro on serine at a stoichiometry of approximately 1 mol of phosphate per mol of p85. This phosphorylation results in a three- to sevenfold decrease in PtdIns 3-kinase activity. Dephosphorylation with protein phosphatase 2A reverses the inhibition. This suggests that the association of protein phosphatase 2A with middle T antigen may function to activate PtdIns 3-kinase.
Unlinking the methylome pattern from nucleotide sequence, revealed by large-scale in vivo genome engineering and methylome editing in medaka fish (2017)

The heavily methylated vertebrate genomes are punctuated by stretches of poorly methylated DNA sequences that usually mark gene regulatory regions. It is known that the methylation state of these regions confers transcriptional control over their associated genes. Given its governance on the transcriptome, cellular functions and identity, genome-wide DNA methylation pattern is tightly regulated and evidently predefined. However, how is the methylation pattern determined in vivo remains enigmatic. Based on in silico and in vitro evidence, recent studies proposed that the regional hypomethylated state is primarily determined by local DNA sequence, e.g., high CpG density and presence of specific transcription factor binding sites. Nonetheless, the dependency of DNA methylation on nucleotide sequence has not been carefully validated in vertebrates in vivo. Herein, with the use of medaka (Oryzias latipes) as a model, the sequence dependency of DNA methylation was intensively tested in vivo. Our statistical modeling confirmed the strong statistical association between nucleotide sequence pattern and methylation state in the medaka genome. However, by manipulating the methylation state of a number of genomic sequences and reintegrating them into medaka embryos, we demonstrated that artificially conferred DNA methylation states were predominantly and robustly maintained in vivo, regardless of their sequences and endogenous states. This feature was also observed in the medaka transgene that had passed across generations. Thus, despite the observed statistical association, nucleotide sequence was unable to autonomously determine its own methylation state in medaka in vivo. Our results apparently argue against the notion of the governance on the DNA methylation by nucleotide sequence, but instead suggest the involvement of other epigenetic factors in defining and maintaining the DNA methylation landscape. Further investigation in other vertebrate models in vivo will be needed for the generalization of our observations made in medaka.
CREATIVITY: SNOWFLAKES AND CIRCLES IN INFORMATION MANAGEMENT (1993)

Based on the premiss that, as technology gradually takes over most of the clerical functions of management, the one function which computers and automation may never replicate is the creativity of the human mind. Examines the implications of the management of creativity for information managers in the 1990s and beyond. This is achieved by the application of an American model of creativity to information work, the outline of a strategy concerning the introduction of creativity to the organization and finally a consideration of how creativity can enhance the decision‐making process.
Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations (2013)

Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.
GABAergic inhibition of endogenous dopamine release measured in vivo with 11C-raclopride and positron emission tomography (1992)

Extensive neuroanatomical, neurophysiological, and behavioral evidence demonstrates that GABAergic neurons inhibit endogenous dopamine release in the mammalian corpus striatum. Positron emission tomography (PET) studies in adult female baboons, using the dopamine D2-specific radiotracer 11C-raclopride, were undertaken to assess the utility of this imaging technique for measuring these dynamic interactions in vivo. 11C-raclopride binding was imaged prior to and following the administration of either gamma-vinyl-GABA (GVG), a specific suicide inhibitor of the GABA-catabolizing enzyme GABA transaminase, or lorazepam, a clinically prescribed benzodiazepine agonist. Striatal 11C-raclopride binding increased following both GVG and lorazepam administration. This increase exceeded the test/retest variability of 11C-raclopride binding observed in the same animals. These findings confirm that changes in endogenous dopamine concentrations resulting from drug-induced potentiation of GABAergic transmission can be measured with PET and 11C-raclopride. Finally, this new strategy for noninvasively evaluating the functional integrity of neurophysiologically linked transmitter systems with PET supports its use as an approach for assessing the multiple mechanisms of drug action and their consequences in the human brain.
DOXO-EMCH (INNO-206): the first albumin-binding prodrug of doxorubicin to enter clinical trials (2007)

The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that demonstrates superior antitumor efficacy in murine tumor models and a favorable toxicity profile in mice, rats and dogs, including significantly reduced cardiotoxicity. After intravenous administration, DOXO-EMCH binds rapidly to the Cys-34 position of circulating albumin and accumulates in solid tumors due to passive targeting. In a clinical Phase I study, the dose of doxorubicin could be increased by a factor of 4.5-340 mg/m(2) when 75 mg/m(2) of free doxorubicin is considered to be the dose that can be administered as a single agent concomitant with the typical spectrum of side effects (i.e., myelotoxicity and mucositis). DOXO-EMCH was able to induce tumor regressions in anthracycline-sensitive tumors (i.e., breast cancer, small cell lung cancer and sarcoma). Phase II studies will be initiated at the beginning of 2007.
Advanced Glycation End Products (2006)

Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis. The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes upregulation of the transcription factor nuclear factor-kappaB and its target genes. Soluble AGEs activate monocytes, and AGEs in the basement membrane inhibit monocyte migration. AGE-bound RAGE increases endothelial permeability to macromolecules. AGEs block nitric oxide activity in the endothelium and cause the production of reactive oxygen species. Because of the emerging evidence about the adverse effects of AGEs on the vasculature of patients with diabetes, a number of different therapies to inhibit AGEs are under investigation.
Functional Magnetic Stimulation of the Abdominal Muscles in Humans (1999)

Functional magnetic stimulation (FMS) of the thoracic nerve roots to simulate cough has been suggested as a treatment approach in patients unable to voluntarily activate the abdominal muscles. However, factors that could influence the efficacy of FMS in clinical use have not been evaluated. In the present investigation we studied train length, posture, and frequency to determine the optimal stimulation protocol. We also evaluated the use of a valve at the mouth to enhance glottic function and investigated whether lung volume at the time of stimulation would influence the tension generated by the abdominal muscles. Studies were performed using a Magstim rapid stimulator augmented by four booster packs in nine healthy subjects; we measured the change in gastric (DeltaPga(FMS)), esophageal (DeltaPes(FMS)), and mouth pressure and expiratory flow. With our apparatus pressure generation was maximized by having a train length of at least 300 ms and a frequency of 25 Hz. Posture and valve use were not important determinants of DeltaPga(FMS) or DeltaPes(FMS). Lung volume exerted only a minor influence on DeltaPga(FMS), but the ratio DeltaPes(FMS):DeltaPga(FMS) was increased at TLC compared with FRC. Expiratory flow was increased by adopting a seated posture and using an occlusion valve with an opening threshold close to the maximum DeltaPes(FMS) generated by the stimulus train; however, expiratory flow was susceptible to interference from glottic incoordination. Representative results (with train length 600 ms, 25 Hz, and 100% power, seated) were mean DeltaPga(FMS), 166 cm H(2)O; mean DeltaPes(FMS), 108 cm H(2)O; and mean expiratory flow, 311 L/min. We confirm that FMS of the abdominal muscles can generate a substantial positive intra-abdominal and intrathoracic pressure and, consequently, expiratory flow in normal subjects.
Metabonomic Study of Aristolochic Acid-Induced Nephrotoxicity in Rats (2006)

This paper describes a metabonomic study characterizing the nephrotoxicity induced by aristolochic acid (AA), a suspected kidney toxicant. For these studies, we examined the biochemical compositions of AA-treated rat urine using LC-MS and pattern recognition methods. The biochemical and histological patterns of rat groups treated with different AA sources showed distinct differences from those of the control group. Certain metabolic pathways, such as homocysteine formation and the folate cycle were significantly accelerated, while others, including arachidonic acid biosynthesis, were decreased. A subset-validation procedure using linear discriminant analysis (LDA) and selected predictive variables indicated that approximately 95% of the treated and nontreated rat urine samples were classified correctly into their respective treatment groups. The results suggested that this metabonomic approach is a promising methodology for the rapid in vivo screening of nephrotoxicity associated with ingesting multi-ingredient medicinal herb supplements, and provides a valid method for comprehending the chemical-induced perturbations in the metabolic network and the networked lesions.
Control of a Surface Photochemical Process by Fractal Electron Transport Across the Surface:  O2 Photodesorption from TiO2(110) (2006)

The photodesorption of O(2) from TiO(2)(110) has been found to exhibit fractal kinetic behavior. The rate coefficient for photodesorption is measured throughout the entire experiment and is shown to decrease by a factor of approximately 100 over a time period of approximately 250 s. A model is proposed in which the electrons associated with O-vacancy defects on the surface percolate from vacancy site to vacancy site via the filled orbitals at these sites to neutralize photoproduced holes. This electron percolation, causing electron-hole recombination, reduces the efficiency of charge transfer between a photoproduced hole and an O(2)(-)(a) species localized at a vacancy defect site, causing the rate of O(2) photodesorption to follow a fractal rate law. We postulate that the fractal electron conduction path across the surface is one-dimensional.
Muscle wasting associated with cancer cachexia is linked to an important activation of the atp‐dependent ubiquitin‐mediated proteolysis (1995)

Rats bearing the Yoshida AH-130 ascites hepatoma for 7 days showed an important decrease in muscle mass--over 30% in gastrocnemius and extensor digitorum longus (EDL)--in relation to non-tumour-bearing controls, which is associated with an increased proteolytic rate in in vitro incubation. In order to identify the precise biochemical process which was involved, we measured different proteolytic systems in incubated EDL muscles. The capacity for intralysosomal proteolysis, as measured by sensitivity to methylamine, was not increased in tumour-bearing rats, suggesting that the mechanism involved in the increased proteolytic rate was extralysosomal. Incubations using the Ca2+ ionophore A23187 revealed no change in the activity of calcium-dependent proteases as a consequence of tumour growth. Finally, muscle incubation in an ATP-depleted medium allowed us to conclude that energy-dependent proteases were involved in the activation of muscle proteolysis in tumour-bearing rats. In particular, the ubiquitin-dependent proteolytic system is involved, since there is an important increase in ubiquitin conjugates in the skeletal muscle of tumour-bearing rats. It may thus be suggested that extralysosomal ATP- and ubiquitin-dependent proteases underlie the biochemical mechanism of muscle wastage associated with cancer cachexia.
Hardware Improvements To The Helmet Mounted Projector On The Visual Display Research Tool (VDRT) At The Naval Training Systems Center (1989)

The Visual Pisplay Research Tool includes a helmet mounted projector for the display of flight simulation Area-of-Interest imagery on a 10 foot radius dome. The imagery is transmitted to the helmet using two coherent fibre optic ribbons. Some improvements have been made to the fibre optic system and to the helmet fit. The imagery is head and eye slaved and the concepts for image positioning and stabilisation are described.
ChemInform Abstract: A Simple Stereoselective Synthesis of Aplysinopsin Analogues. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts. (1993)

Allogeneic newborn neural retinal grafts implanted in the subretinal space and vitreous cavity experience immune privilege and induce deviant immune responses resembling anterior chamber associated immune deviation.
Ubiquitin in Neurodegenerative Diseases (1993)

Immunochemical staining to detect ubiquitin has become an essential technique in evaluating neurodegenerative processes. Age related staining is seen in myelin, in nerve processes in lysosome-related dense bodies, and in corpora amylacea. There is a constant association between filamentous inclusions and the presence of ubiquitin. Intermediate filaments associated with ubiquitin, alpha B crystallin and enzymes of the ubiquitin pathway are the basis of Lewy bodies and Rosenthal fibres, as well as related bodies outside the nervous system. Neurofibrillary tangles in diverse diseases are associated with ubiquitin as are several other tau containing inclusions in both neurones and glia. Inclusions in motor neurones and non-motor cortex characterizing amyotrophic lateral sclerosis (ALS) and certain related forms of frontal lobe dementia can only be readily detected by anti-ubiquitin. Anti-ubiquitin also identifies both filamentous and lysosomal structures in neuronal processes as well as in some swollen neurones. Involvement of ubiquitin-containing elements of the lysosomal system appears important in pathogenesis of prion encephalopathies. Despite great advances in understanding cell biology of the ubiquitin pathway there are as yet few insights into the precise role played by ubiquitin in neuronal disease.
Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment (2000)

Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin. Genetic polymorphisms in CYP2C9 producing variants with altered catalytic properties have been identified. Patients (n = 561) with a target international normalized ratio (INR) of 2.5 who had been treated with warfarin for more than 2 months were anonymously genotyped for the wild-type CYP2C9*1 allele and the 2C9*2 and 2C9*3 variants. The mean maintenance dose of warfarin in patients who were wild-type for both alleles was 5.01 mg. The maintenance dose of warfarin was significantly related to genotype (Kruskall-Wallis, chi(2) = 17.985, P =.001) with mean maintenance doses in patients with variant alleles between 61% and 86% of that in wild-type patients. The odds ratio for the 2C9*2 allele in patients with a maintenance dose of 1. 5 mg or less was 5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD of the mean INR, percentage of high INRs, and person-time spent in range were determined as parameters of stability. There was no difference between patients grouped according to genotype for any parameter of stability. This study confirmed an association between CYP2C9 genotype and warfarin sensitivity. However, the possession of a variant allele does not increase the likelihood of severe over-anticoagulation or stability of anticoagulation during long-term therapy. (Blood. 2000;96:1816-1819)
Immunostimulating capacities of stabilized RNA molecules (2004)

Since direct injection of naked mRNA induces an immune response, we tested the capacity of RNA to signal danger. We show here that mRNA molecules that are protected from immediate degradation either through interaction with cationic proteins (trans protection) or through chemical modification of the phosphodiester backbone (phosphorothioate RNA; cis protection) act as sequence-independent danger signals on mouse DC. As opposed to CpG DNA, the cis-stabilized RNA is degraded in a few minutes, does not activate B cells and, in contrast to double-stranded RNA, requires MyD88 for activation of the DC. We postulate that phosphorothioate RNA, which mimics trans-stabilized RNA, is a new PAMP.