gebhart/patrepeval huggingface dataset:
High-frequency oscillations during human focal seizures (2006)

Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.
Discovery of 3-Alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitriles as Selective, Orally Bioavailable CHK1 Inhibitors (2012)

Inhibitors of checkpoint kinase 1 (CHK1) are of current interest as potential antitumor agents, but the most advanced inhibitor series reported to date are not orally bioavailable. A novel series of potent and orally bioavailable 3-alkoxyamino-5-(pyridin-2-ylamino)pyrazine-2-carbonitrile CHK1 inhibitors was generated by hybridization of two lead scaffolds derived from fragment-based drug design and optimized for CHK1 potency and high selectivity using a cell-based assay cascade. Efficient in vivo pharmacokinetic assessment was used to identify compounds with prolonged exposure following oral dosing. The optimized compound (CCT244747) was a potent and highly selective CHK1 inhibitor, which modulated the DNA damage response pathway in human tumor xenografts and showed antitumor activity in combination with genotoxic chemotherapies and as a single agent.
An Efficient Class of P,N‐Type “PhMezole‐phos” Ligands: Applications in Palladium‐Catalyzed Suzuki Coupling of Aryl Chlorides (2012)

Abstract This study describes an efficient class of hemilabile benzimidazolyl–phosphane ligands that can be easily accessed from commercially available and inexpensive starting materials. The application of this ligand array in the palladium‐catalyzed Suzuki–Miyaura coupling reaction of aryl chlorides with arylboronic acids is described. The palladium catalyst generated from this hemilabile phosphane is highly effective in the Suzuki–Miyaura coupling of unactivated aryl chlorides, and catalyst loadings as low as 1 ppm can be achieved.
Sphingolipid Regulation of Tissue Fibrosis (2012)

Bioactive sphingolipids, such as sphingosine 1-phosphate (S1P), dihydrosphingosine 1-phosphate (dhS1P) and ceramide, regulate a diverse array of cellular processes. Many of these processes are important components of wound-healing responses to tissue injury, including cellular apoptosis, vascular leak, fibroblast migration, and TGF-β signaling. Since over-exuberant or aberrant wound-healing responses to repetitive injury have been implicated in the pathogenesis of tissue fibrosis, these signaling sphingolipids have the potential to influence the development and progression of fibrotic diseases. Here we review accumulating in vitro and in vivo data indicating that these lipid mediators can in fact influence fibrogenesis in numerous organ systems, including the lungs, skin, liver, heart, and eye. Targeting these lipids, their receptors, or the enzymes involved in their metabolism consequently now appears to hold great promise for the development of novel therapies for fibrotic diseases.
Nonmammalian genomic analysis : a practical guide (1996)

Introduction to pulsed field gels, preparation, and analysis of large DNA, J.S. Lee, B. Birren, and E. Lai electrophoretic karyotyping in fungi, K. Dewar, L. Bernier, and R. Levesque isolation and analysis of high molecular weight DNA from plants, M. Ganal generating and using DNA markers in plants, J.A. Rafalski, M. Morgante, W. Powell, J.M. Vogel, and S.V. Tingey genome mapping of protozoan parasites by linking clones, S. Morzaria mapping and analysis of bacterial genomes, U. Romling, R. Fislage, and B. Tummler cosmid cloning with small genomes, R. Wenzal and R. Herrmann construction of P1 artificial chromosome (PAC) libraries from lower vertebrates, C.T. Amemiya, T. Ota, and G.W. Litman the selection of chromosome-specific DNA clones from African trypanosome genomic libraries, S. Melville, N. Shepherd, C. Gerrard, and R. Le Page analysis of the dictyostelium discoideum genome, A. Kuspa and W. Loomis integrated genome mapping by hybridization techniques, J.D. Hoheisel, E. Maier, R. Mott and H. Lehrach.
Size- and Shape-Controlled Magnetic (Cr, Mn, Fe, Co, Ni) Oxide Nanocrystals via a Simple and General Approach (2004)

A general, reproducible, and simple strategy using generic chemicals is introduced for controlling the size, shape, and size distribution of oxide nanocrystals. The reaction system was generally composed of the metal fatty acid salts, the corresponding fatty acids, and a hydrocarbon solvent. The method is based on the pyrolysis of metal fatty acid salts, the most common metal compounds compatible with nonaqueous solutions. Synthesis of nearly monodisperse Fe3O4 nanocrystals in a large size range (3−50 nm) was developed as the model system. The method was further applied for the growth of oxide nanocrystals of the other magnetic metals in the fourth rowCr2O3, MnO, Co3O4, and NiO nanocrystals. The size and shape control of the nanocrystals were achieved by varying the reactivity and concentration of the precursors. The reactivity was tuned by changing the chain length and concentration of the ligands, the fatty acids. Alcohols or primary amines could be used as the activation reagents when a given metal fatty acid salt was not sufficiently active under selected reaction conditions.
I/O deduplication: utilizing content similarity to improve I/O performance (2010)

Duplication of data in storage systems is becoming increasingly common. We introduce I/O Deduplication, a storage optimization that utilizes content similarity for improving I/O performance by eliminating I/O operations and reducing the mechanical delays during I/O operations. I/O Deduplication consists of three main techniques: content-based caching, dynamic replica retrieval, and selective duplication. Each of these techniques is motivated by our observations with I/O workload traces obtained from actively-used production storage systems, all of which revealed surprisingly high levels of content similarity for both stored and accessed data. Evaluation of a prototype implementation using these workloads revealed an overall improvement in disk I/O performance of 28-47% across these workloads. Further breakdown also showed that each of the three techniques contributed significantly to the overall performance improvement.
Slc25a13-Knockout Mice Harbor Metabolic Deficits but Fail To Display Hallmarks of Adult-Onset Type II Citrullinemia (2003)

Adult-onset type II citrullinemia (CTLN2) is an autosomal recessive disease caused by mutations in SLC25A13, the gene encoding the mitochondrial aspartate/glutamate carrier citrin. The absence of citrin leads to a liver-specific, quantitative decrease of argininosuccinate synthetase (ASS), causing hyperammonemia and citrullinemia. To investigate the physiological role of citrin and the development of CTLN2, an Slc25a13-knockout (also known as Ctrn-deficient) mouse model was created. The resulting Ctrn-/- mice were devoid of Slc25a13 mRNA and citrin protein. Liver mitochondrial assays revealed markedly decreased activities in aspartate transport and the malate-aspartate shuttle. Liver perfusion also demonstrated deficits in ureogenesis from ammonia, gluconeogenesis from lactate, and an increase in the lactate-to-pyruvate ratio within hepatocytes. Surprisingly, Ctrn-/- mice up to 1 year of age failed to show CTLN2-like symptoms due to normal hepatic ASS activity. Serological measures of glucose, amino acid, and ammonia metabolism also showed no significant alterations. Nitrogen-loading treatments produced only minor changes in the hepatic ammonia and amino acid levels. These results suggest that citrin deficiency alone may not be sufficient to produce a CTLN2-like phenotype in mice. These observations are compatible, however, with the variable age of onset, incomplete penetrance, and strong ethnic bias seen in CTLN2 where additional environmental and/or genetic triggers are now suspected.
Differential regulation and properties of angiopoietin-like proteins 3 and 4 (2005)

Angiopoietin-like protein 3 and 4 (Angptl3 and Angptl4) are two members of the angiopoietin-like family of proteins. These two closely related proteins have been reported to similarly affect lipid metabolism through their capacity to inhibit lipoprotein lipase. We undertook a series of studies to compare the structure, function, and regulation of Angptl3 and Angptl4. Previously, we reported that Angptl4 exists as variable-sized oligomers that contain intermolecular disulfide bonds. We now have evidence that although there are no intermolecular disulfide bonds evident in Angptl3, higher molecular weight forms do exist. In addition, Angptl4 exhibits a widespread distribution of tissue expression, while Angptl3 is exclusively expressed in the liver. Treatments with various ligands of nuclear receptors reveal that Angptl3 is a target gene of liver X receptor, while Angptl4 expression is activated by ligands of all peroxisome proliferator-activated receptors. Expression of Angptl4 in adipose tissue and liver is induced by fasting, while Angptl3 expression is not appreciably affected by nutritional status. We suggest that the differential regulation of Angptl3 and Angptl4 by sites of expression, nutritional status, and ligands of nuclear receptors may confer unique roles of each in lipoprotein metabolism.
The role of glutamine oxidation and the purine nucleotide cycle for adaptation of tumour energetics to the transition from the anaerobic to the aerobic state (1988)

It is proposed that the purine nucleotide cycle and glutamine oxidation play a key role in the adaptation of tumour energetics to the transition from the anaerobic to the aerobic state. In support of this proposal, it was found that glutamine and inosine markedly increase total adenylates in the presence of oxygen, whereas the addition of hadacidin abolishes this effect. Transition of the cells from the anaerobic to the aerobic state, and vice versa, in the presence of glutamine plus inosine revealed that there are two components of the adenine nucleotide pool, one which is stable and the other which is variable and responds to the aerobic-anaerobic transition. This part of the pool undergoes degradation or resynthesis owing to activation of the enzymes of the purine nucleotide cycle. Resynthesis of the pool is accompanied by substantial net utilization of aspartate, which is produced by glutamine oxidation. This is supported by the experiments in which the cells were alternately incubated with nitrogen or oxygen, demonstrating that hadacidin significantly decreased utilization of aspartate and regeneration of ATP owing to inhibition of adenylosuccinate synthase.
Glucose-Sensitive Polypyrrole/Poly(Styrenesulfonate) Films Containing Co-immobilized Glucose Oxidase and (Ferrocenylmethyl) Trimethylammonium Bromide (1995)

Abstract Glucose oxidase (GOx) and (ferrocenylmethyl) trimethylammonium bromide (FcBr) were co-immobilized into polypyrrole (PP)/poly(styrenesulfonate) (PSS) films during the electropolymerization of pyrrole. PSS was employed as a partial dopant anion for PP (along with Br−) and as an electrostatic binder for the cationic mediator (FcBr). The electropolymerization of the PP/PSS film was carried out at +0.8 V vs SCE in a 5-cm3 aqueous solution of glucose oxidase (1 mg°Cm−3), FcBr (1 mM), PSS (1 mM), and pyrrole (50 mM) at 5°C. These enzymemediator derivatized electroactive polymer films (ca. 0.5-2 μm thick) coated on Pt electrodes showed sensitivities to glucose without the use of any mediator in solution, and can be used as amperometric glucose sensors. The responses of the resulting electrodes (0.24 cm2 Pt plate with the polymer film) to glucose were measured amperometrically in pH 7, 0.1 M phosphate buffer solution at 5°C, and a constant potential (+0.5 V vs SCE) by using a Pt coil counterelectrode, with a saturated calomel electrode (SCE) as the reference. Co-immobilization of GOx and FcBr in PP/PSS films, responses of the PP/PSS/FcBr/GOx film on Pt electrodes to glucose, and the effect of the temperature on glucose response are discussed.
Differential Expression of Cholesterol Hydroxylases in Alzheimer's Disease (2004)

Cholesterol is eliminated from neurons by oxidization, which generates oxysterols. Cholesterol oxidation is mediated by the enzymes cholesterol 24-hydroxylase (CYP46A1) and cholesterol 27-hydroxylase (CYP27A1). Immunocytochemical studies show that CYP46A1 and CYP27A1 are expressed in neurons and some astrocytes in the normal brain, and CYP27A1 is present in oligodendrocytes. In Alzheimer's disease (AD), CYP46A1 shows prominent expression in astrocytes and around amyloid plaques, whereas CYP27A1 expression decreases in neurons and is not apparent around amyloid plaques but increases in oligodendrocytes. Although previous studies have examined the effects of synthetic oxysterols on the processing of amyloid precursor protein (APP), the actions of the naturally occurring oxysterols have yet to be examined. To understand the role of cholesterol oxidation in AD, we compared the effects of 24(S)- and 27-hydroxycholesterol on the processing of APP and analyzed the cell-specific expression patterns of the two cholesterol hydroxylases in the human brain. Both oxysterols inhibited production of Abeta in neurons, but 24(S)-hydroxycholesterol was approximately 1000-fold more potent than 27-hydroxycholesterol. The IC(50) of 24(S)-hydroxycholesterol for inhibiting Abeta secretion was approximately 1 nm. Both oxysterols induced ABCA1 expression with IC(50) values similar to that for inhibition of A beta secretion, suggesting the involvement of liver X receptor. Oxysterols also inhibited protein kinase C activity and APP secretion following stimulation of protein kinase C. The selective expression of CYP46A1 around neuritic plaques and the potent inhibition of APP processing in neurons by 24(S)-hydroxycholesterol suggests that CYP46A1 affects the pathophysiology of AD and provides insight into how polymorphisms in the CYP46A1 gene might influence the pathophysiology of this prevalent disease.
Photodynamic therapy: the clinical perspective. Review on applications for control of diverse tumorous and non-tumorous diseases. (1997)

Photodynamic therapy (PDT) is an innovative and attractive modality for the treatment of small and superficial tumours. PDT, as a multi-modality treatment procedure, needs both, a photosensitizer with distinct tumour selectivity and a powerful light source that matches the absorption spectrum of the photosensitizer. The purified haematoporphyrin derivative Photofrin is so far the only sensitizer approved for phase III/IV clinical trials. Major drawbacks of this product are: lack of chemical homogeneity, skin phototoxicity, unfavourable physicochemical properties and poor selectivity in terms of uptake and retention by tumour versus normal cells. Most second generation photosensitizers, including the phthalocyanines, show an increased photodynamic efficiency in the treatment of animal tumours and reduced phototoxic side effects. In 1997, there were more than half a dozen new sensitizers in or about to start clinical trials. To introduce the basic principles of photodynamic therapy, the current review article discusses in some more detail the treatment of endobronchial lung cancer, one of the leading indications of PDT. Moreover, a broad overview is given on the use of PDT for treatment of a wide variety of tumorous and nontumorous diseases, including new strategies for control of rheumatoid arthritis and application of PDT for extracorporeal bone marrow purging.
Antisense oligonucleotides targeted against asialoglycoprotein receptor 1 block human hepatitis B virus replication (2005)

Chronic hepatitis B virus (HBV) infection is a major worldwide public health problem. Better therapeutics and treatment strategies are urgently needed because of ineffective clinical treatment. Our previous study showed that asialoglycoprotein receptor 1 (ASGPR1) was upregulated by HBV but downregulated by lamivudine in HepG2.2.15 cells. It has also been reported that ASGPR is a candidate receptor for HBV attachment to hepatocytes. Therefore, as a major subunit of ASGPR, ASGPR1, might be a potential target for anti-HBV drugs. To validate this hypothesis, antisense oligonucleiotides (ASODNs) were used to downregulate ASGPR1 level in HepG2.2.15 cells. By using the MFOLD web server and BLAST searches, five ASODNs theoretically targeting ASGPR1 were selected. After 72 h post-transfection, HBV-DNA level in cell medium were examined by real-time polymerase chain reaction (PCR). Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) were detected using enzyme-linked immunosorbent assay (ELISA). ASGPR1 mRNA and protein level were measured by semi-quantitative reverse transcriptase (RT)-PCR and Western blot analysis respectively. The results showed that ASODN2 significantly downregulated ASGPR1 level. It also reduced HBV-DNA, HBsAg and HBeAg level in cell medium as observed with lamivudine. In contrast, the sense sequence and scrambled sequence of ASODN2 had no effect on ASGPR1 and HBV markers in HepG2.2.15 cells. This indicated that ASODN2 could specifically reduce HBV replication in vitro. Additionally, cell proliferation and apoptosis assay suggested that downregulation of ASGPR1 did not affect cell viability. We, therefore, proposed that ASODNs targeted against ASGPR1 could block HBV replication without the influence of other changes, and ASGPR1 could be targeted for anti-HBV drug development.
Development of “Stainless Aluminum” (1991)

A process for surface modification of Al‐based materials is described which involves immersion in boiling and , followed by anodic polarization in a molybdate solution. Each of these three steps is carried out for 2 h. Al 6061 treated in this manner did not show any signs of uniform or localized corrosion during immersion in for 60 days. A sample with a scratch in the modified surface also did not show any corrosion after 25 days in . Since this surface modification process produces exceptional corrosion resistance, it should be considered as a candidate for the replacement of chromate conversion coatings.
Herpes simplex Virus (1997)

CNS infections caused by human herpesvirus 1 and human herpesvirus 2-herpes simplex virus type 1 and herpes simplex virus type 2--are reviewed. The major diseases associated with these viruses are meningitis and encephalitis. Two forms of encephalitis are known, neonatal encephalitis and encephalitis occurring after the neonatal period. Both diseases are associated with high mortality and morbidity and require prompt diagnosis and aggressive antiviral chemotherapy. Methods for the specific diagnosis of these infections are reviewed and the value of intrathecal antibody assay and nucleic acid amplification techniques are emphasised.
Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial (2014)

Vagal nerve stimulation as delivered in the NECTAR-HF trial failed to demonstrate a significant effect on primary and secondary endpoint measures of cardiac remodelling and functional capacity in symptomatic heart failure patients, but quality-of-life measures showed significant improvement.
Neutralizing antibodies to granulocyte–macrophage colony‐stimulating factor, interleukin‐1α and interferon‐α but not other cytokines in human immunoglobulin preparations (2000)

Human immunoglobulin preparations are used therapeutically for various disorders. Such therapy is generally safe but adverse effects occasionally occur in recipients. It has been suggested that antibodies to cytokines present in clinical immunoglobulin products may contribute to undesirable effects in recipients. Therefore, we investigated intravenous and intramuscular immunoglobulin products for the presence of cytokine-specific neutralizing antibodies. Using validated bioassays, we detected neutralizing activity against human granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-alpha2a (IFN-alpha2a) and interleukin-1alpha (IL-1alpha) in immunoglobulin products. We found no neutralization of granulocyte colony-stimulating factor, macrophage colony-stimulating factor, stem cell factor, IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-9, IL-10, IL-12, tumour necrosis factor-alpha, oncostatin M (OSM) and IFN-gamma. Most batches which neutralized IFN-alpha2a activity also neutralized other IFN-alpha subtypes, IFN-omega and IFN-beta. Most products (94%) neutralized the biological activity of GM-CSF. No correlation between batches and their ability to neutralize bioactivities of GM-CSF, IFN-alpha2a and IL-1alpha was found. This neutralizing activity could be traced to plasma pools used for manufacture of immunoglobulins. The neutralization was mediated by specific cytokine antibodies contained within immunoglobulin products as it was present in specific immunoglobulin G (IgG) fractions eluted from cytokine affinity chromatography columns. Specific binding of such IgG fractions to cytokines in immunoblots and in enzyme-linked immunosorbent assays (ELISAs) was observed. This contrasts with the broad non-specific recognition of cytokine proteins observed using unfractionated immunoglobulins in ELISAs. This is the first comprehensive study showing the presence of neutralizing antibodies against GM-CSF, IL-1alpha, or IFN-alpha2a in immunoglobulin products.
Stimulated Human Phagocytes Produce Cytogenetic Changes in Cultured Mammalian Cells (1983)

CHRONIC inflammation can be associated with cancer.1 Phagocytes in inflammatory lesions enzymatically reduce oxygen to reactive metabolites, which include Superoxide anions, hydrogen peroxide, and hydroxyl radicals. These reactive species kill microorganisms, damage DNA, and lyse mammalian cells.2 3 4 5 6 Sublethal damage to genetic material in inflamed foci caused by phagocyte-derived oxygen metabolites may be one mechanism by which cancer arises in the presence of inflammation. The observation that human phagocytes are important in this mutagenic process7 8 9 is consistent with this idea, since there is a strong correlation between mutagenesis and carcinogenesis.10 In this paper we report that human phagocytes that are activated . . .