gebhart/patrepeval huggingface dataset:
Ring‐Sulfonated Poly(thienothiophene) (2005)

Ring sulfonation of a poly(thienothiophene) produces a stable, low‐bandgap (&lt; 1.2 eV), water‐processable, intrinsically conductive polymer. The optical properties of the polymer can be easily modified by varying the sulfonation level and optical‐bandgap tuning can also be achieved through the use of a polycation. When used as the polyanion in layer‐by‐layer‐assembled films with polyethyleneimine, the optical absorption properties and intensity remain unchanged for seventeen months. Stability combined with an absorption maximum located within the range for peak solar flux could render these polymers as potential dyes for solar‐energy conversion applications.
Cerivastatin. (2002)

Cerivastatin is a synthetic and enantiomerically pure 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. It has been recognized for its high pharmacologic potency, uncomplicated pharmacokinetic profile, and low drug-interaction potential. The efficacy of cerivastatin has been demonstrated in a number of clinical trials involving patients with primary hypercholesterolemia and mixed dyslipidemia. Cerivastatin was found to have dose-dependent reduction in total cholesterol and low-density lipoprotein (LDL) cholesterol. At the 0.4 mg daily dose, cerivastatin was found to lower LDL cholesterol by approximately 35% (mean reductions of 33-39%). The triglyceride-lowering effect of cerivastatin is also dose dependent; however, there is a much stronger association between baseline triglyceride levels and the triglyceride-lowering effect of cerivastatin. A dosage of 0.4 mg daily has been shown to reduce triglycerides by a mean of 28% in patients with baseline triglyceride levels of > 300 mg/dL. At the time of its initial approval by the US Food and Drug Administration (FDA) in 1997, cerivastatin was available only in 0.2 mg and 0.3 mg strengths. The recent FDA approval of the 0.4-mg strength dose has made cerivastatin a more competitive drug in lipid-lowering efficacy among the HMG-CoA reductase inhibitors.
Solid-Phase Microextraction and the Human Fecal VOC Metabolome (2011)

The diagnostic potential and health implications of volatile organic compounds (VOCs) present in human feces has begun to receive considerable attention. Headspace solid-phase microextraction (SPME) has greatly facilitated the isolation and analysis of VOCs from human feces. Pioneering human fecal VOC metabolomic investigations have utilized a single SPME fiber type for analyte extraction and analysis. However, we hypothesized that the multifarious nature of metabolites present in human feces dictates the use of several diverse SPME fiber coatings for more comprehensive metabolomic coverage. We report here an evaluation of eight different commercially available SPME fibers, in combination with both GC-MS and GC-FID, and identify the 50/30 µm CAR-DVB-PDMS, 85 µm CAR-PDMS, 65 µm DVB-PDMS, 7 µm PDMS, and 60 µm PEG SPME fibers as a minimal set of fibers appropriate for human fecal VOC metabolomics, collectively isolating approximately 90% of the total metabolites obtained when using all eight fibers. We also evaluate the effect of extraction duration on metabolite isolation and illustrate that ex vivo enteric microbial fermentation has no effect on metabolite composition during prolonged extractions if the SPME is performed as described herein.
A CRISPR/Cas-Mediated Selection-free Knockin Strategy in Human Embryonic Stem Cells (2015)

The development of new gene-editing tools, in particular the CRISPR/Cas system, has greatly facilitated site-specific mutagenesis in human embryonic stem cells (hESCs), including the introduction or correction of patient-specific mutations for disease modeling. However, integration of a reporter gene into an endogenous locus in hESCs still requires a lengthy and laborious two-step strategy that involves first drug selection to identify correctly targeted clones and then excision of the drug-resistance cassette. Through the use of iCRISPR, an efficient gene-editing platform we recently developed, this study demonstrates a knockin strategy without drug selection for both active and silent genes in hESCs. Lineage-specific hESC reporter lines are useful for real-time monitoring of cell-fate decisions and lineage tracing, as well as enrichment of specific cell populations during hESC differentiation. Thus, this selection-free knockin strategy is expected to greatly facilitate the use of hESCs for developmental studies, disease modeling, and cell-replacement therapy.
Free Radicals, Antioxidants and Eye Diseases: Evidence from Epidemiological Studies on Cataract and Age-Related Macular Degeneration (2010)

Cataract and age-related macular degeneration (AMD) are the major causes of vision impairment and blindness worldwide. Both conditions are strongly age related with earlier signs (usually asymptomatic) occurring in middle age and becoming severer and more prevalent with increasing age. The aetiology of these conditions is thought to fit with the 'free radical theory' of ageing which postulates that ageing and age-related diseases result from the accumulation of cellular damage from reactive oxygen species (ROS). Mitochondrial energy production is a major source of endogenous ROS. External sources of ROS include environmental sources especially solar radiation, biomass fuels and tobacco smoking. There is strong evidence from epidemiological studies that smoking is a risk factor for both cataract and AMD. There is moderate evidence for an association with sunlight and cataract but weak evidence for sunlight and AMD. The few studies that have investigated this suggest an adverse effect of biomass fuels on cataract risk. The antioxidant defence system of the lens and retina include antioxidant vitamins C and E and the carotenoids lutein and zinc, and there is mixed evidence on their associations with cataract and AMD from epidemiological studies. Most epidemiological studies have been conducted in well-nourished western populations but evidence is now emerging from other populations with different dietary patterns and antioxidant levels.
A 600 kHz electrically-coupled MEMS bandpass filter (2003)

This paper presents a 600 kHz MEMS bandpass filter implemented using electrical coupling of single crystal silicon HARPSS micromechanical resonators. Passive and active filter synthesis approaches based on electrical coupling of capacitive MEMS resonators are introduced and discussed. A third order passive bandpass filter at the center frequency of 600 kHz with a bandwidth of 125 Hz, a stopband rejection of 48 dB, and a 20 dB-shape-factor of 2.1 is demonstrated. A quality factor (Q) enhancement technique based on active electrical cascading of the resonators is also presented. A 3-stage active cascade at 600 kHz demonstrated a 2/spl times/ increase in the effective Q.
Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3). (1993)

The insulin-like growth factor-I (IGF-I) receptor is a member of a large family of transmembrane signal transducing molecules. The defining characteristic of this class of receptors is the intrinsic tyrosine kinase activity of the cytoplasmic domain. While it has been demonstrated that this tyrosine kinase activity is necessary for the action of a number of transmembrane tyrosine kinase receptors, no evidence of this type has been adduced to date with respect to the signaling requirement of the IGF-I receptor. We have now shown that stably transfected NIH-3T3 cell lines overexpressing human IGF-I receptors display increased responses to IGF-I and an IGF-I-mimetic antibody, alpha IR-3, in terms of short, intermediate, and long term actions initiated by activation of the IGF-I receptor. These include receptor autophosphorylation, activation of phosphatidylinositol-3-kinase and 2-deoxyglucose uptake, induction of ornithine decarboxylase gene expression, and stimulation of thymidine incorporation. In short term responses, the kinetics seen with alpha IR-3 were slower than those seen with IGF-I. These effects were severely decreased in clones expressing human IGF-I receptors in which the lysine residue in the ATP-binding site of the tyrosine kinase domain had been mutated to alanine or arginine. This was true for both IGF-I and alpha IR-3. These results indicate that, for all parameters tested, the tyrosine kinase activity of the IGF-I receptor is necessary for activation of the IGF-I-stimulated signal transduction cascade. Additionally, the effects of alpha IR-3 also require tyrosine kinase activity.
Disruption of thelama2Gene in Embryonic Stem Cells: Laminin α2 Is Necessary for Sustenance of Mature Muscle Cells (1998)

Mutations in the gene coding for the alpha 2 chain of laminin-2 and -4 (merosin) cause a severe form of congenital muscular dystrophy in humans and mice. To establish a defined model for in vitro and in vivo studies of the role of laminin alpha 2/merosin in development and cell and tissue function, we generated several lines of mutant embryonic stem (ES) cell with disruption of the laminin alpha 2 chain gene. We find that homozygous mutant ES cells differentiate normally in vitro, giving rise to cardiomyocytes, myotubes, and smooth muscle cells in addition to many other cell types. However, the myotubes that are formed are unstable. They detach, collapse, and degenerate, a process which is initiated at the appearance of the mature, contractile phenotype of the cells. We propose that the detachment and death of contracting myotubes in vitro has its counterpart in vivo and that contraction-induced myofiber damage, along with the lack of survival cues provided by laminin alpha 2/merosin, is a significant contribution to muscle degeneration in merosin-deficient muscular dystrophy.
An architecture for specification-based detection of semantic integrity violations in kernel dynamic data (2006)

The ability of intruders to hide their presence in compromised systems has surpassed the ability of the current generation of integrity monitors to detect them. Once in control of a system, intruders modify the state of constantly-changing dynamic kernel data structures to hide their processes and elevate their privileges. Current monitoring tools are limited to detecting changes in nominally static kernel data and text and cannot distinguish a valid state change from tampering in these dynamic data structures. We introduce a novel general architecture for defining and monitoring semantic integrity constraints using a specification language-based approach. This approach will enable a new generation of integrity monitors to distinguish valid states from tampering.
A New Trimeric Cinchona Alkaloid as a Chiral Phase-Transfer Catalyst for the Synthesis of Asymmetric α-Amino Acids (2005)

A new trimeric cinchona alkaloid, the quaternary ammonium salt, α,α′,α′′-tris[O(9)-allylcinchonidinium-(4-methylphen­oxymethyl)]benzene trichloride, has been synthesized and used as an efficient phase-transfer catalyst in asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester with very good yield (up to 97%) and high enantioselectivity (up to 98%).
Separating business process from user interaction utilizing process-aware XSLT stylesheets (2003)

In the web context, it is difficult to disentangle presentation from process logic, and sometimes even data is not separate from the presentation. Consequently, it becomes crucial to define an abstract model for business processes, and their mapping into an active user interface presentation, using the principle of separation of concern between the process logic, data and its presentation aspects. We endeavour to extend declarative (rule based) XSLT to accommodate the separation of process information from the data structure and presentation, and thus propose to design process aware stylesheets, in a minimally invasive manner. The isolation of the three otherwise entangled aspects of web-processes makes it easy to develop and maintain web-applications in a more independent manner where each individual developer can focus on his/her primary responsibility, like describing the process, maintaining a database, or creating user interface (web-pages) without being levied any substantial effort to learn new technology.
Clinical phenotypes and factor VII genotype in congenital factor VII deficiency (2005)

To investigate the relationship between clinical phenotype, clotting activity (FVIIc) and FVII genotype, a multi-center study of factor VII (FVII) congenital deficiency with centralized genotyping and specific functional assays was carried out. FVII mutations characterized in patients (n=313) were extremely heterogeneous (103 different, 22 novel). Clinical phenotypes ranged from asymptomatic condition, including 15 homozygotes and 14 double heterozygotes, to patients with a severe disease characterized by life-threatening and disabling symptoms (CNS, GI bleeding and hemarthrosis) strongly associated with an early age of presentation. Based on type and number of symptoms we classified 90 'severe' (median FVIIc 1.4%, IQR [Interquartile Range] 0.9-3.8), 83 'moderate' (FVIIc 3%, IQR 1-21.7), and 140 'mild' bleeders (FVIIc 14%, IQR 3-31). The significantly different FVIIc levels, and the decreasing prevalence of homozygotes or double heterozygotes among severe (98%), moderate (84%) and mild (56%) bleeders, further support our classification. The excess of females among moderate bleeders (female/male ratio = 2.6) is attributable to menorrhagia. There was no evidence for modulation of clinical features by frequent functional polymorphisms. Homozygotes for the same mutation (Ala294Val; 11125delC) with similar FVIIc and FXa generation levels, showed striking differences in clinical phenotypes. Our study depicts the ample clinical picture of this rare disorder, proposes a severity classification and provides arguments for the early management of the disease in the severe cases. Genotype-phenotype relationships indicate the presence of major environmental and/or extragenic components modulating expressivity of FVII deficiency.
Selective Interaction of Triazole Derivatives with DWF4, a Cytochrome P450 Monooxygenase of the Brassinosteroid Biosynthetic Pathway, Correlates with Brassinosteroid Deficiency in Planta (2001)

Brassinazole, a synthetic chemical developed in our laboratory, is a triazole-type brassinosteroid biosynthesis inhibitor that induces dwarfism in various plant species. The target sites of brassinazole were investigated by chemical analyses of endogenous brassinosteroids (BRs) in brassinazole-treated Catharanthus roseus cells. The levels of castasterone and brassinolide in brassinazole-treated plant cells were less than 6% of the levels in untreated cells. In contrast, campestanol and 6-oxocampestanol levels were increased, and levels of BR intermediates with hydroxy groups on the side chains were reduced, suggesting that brassinazole treatment reduced BR levels by inhibiting the hydroxylation of the C-22 position. DWF4, which is an Arabidopsis thaliana cytochrome P450 isolated as a putative steroid 22-hydroxylase, was expressed in Escherichia coli, and the binding affinity of brassinazole and its derivatives to the recombinant DWF4 were analyzed. Among several triazole derivatives, brassinazole had both the highest binding affinity to DWF4 and the highest growth inhibitory activity. The binding affinity and the activity for inhibiting hypocotyl growth were well correlated among the derivatives. In brassinazole-treated A. thaliana, the CPD gene involved in BR biosynthesis was induced within 3 h, most likely because of feedback activation caused by the reduced levels of active BRs. These results indicate that brassinazole inhibits the hydroxylation of the C-22 position of the side chain in BRs by direct binding to DWF4 and that DWF4 catalyzes this hydroxylation reaction.
Retroviral-mediated gene transfer corrects very-long-chain fatty acid metabolism in adrenoleukodystrophy fibroblasts. (1995)

Adrenoleukodystrophy (ALD), a lethal demyelinating disease of the brain, is caused by mutations of a gene encoding an ATP-binding transporter, called ALDP, localized in the peroxisomal membrane. It is associated with a defective oxidation of very-long-chain fatty acids, leading to their accumulation in many tissues. This study reports that the retroviral-mediated transfer of the ALD cDNA restored very-long-chain fatty acid oxidation in ALD fibroblasts in vitro following abundant expression and appropriate targeting of the vector-encoded ALDP in peroxisomes. The same method may be used in hematopoietic cells as a further step of a gene therapy approach of ALD.
Increased susceptibility of islets from diabetes-prone Psammomys obesus to the deleterious effects of chronic glucose exposure. (1996)

Patients with noninsulin-dependent diabetes (NIDDM) show an increase in the relative plasma levels of proinsulin and proinsulin conversion intermediates, which is corrected by strict glycemic control. This observation suggests that hyperglycemia per se may be responsible for generating the aberrant plasma hormone profile. The question remains, however, whether a genetic predisposition to NIDDM underlies the failure of the insulin production machinery to meet a prolonged increase in secretory demand. In this study, islet monolayer cultures from the diabetes-prone Psammomys obesus and normal diabetes-resistant rats were exposed to RPMI 1640 medium containing either 11.1 or 33.3 mM glucose; insulin-related peptides were resolved by HPLC. Prolonged exposure (10 days) of rat islets to high glucose resulted in a reduced a secretory response to an acute glucose stimulus associated with a 37% reduction in the insulin content but no change in the proinsulin/insulin ratio. When subjected to a similar protocol, islets from prediabetic Psammomys lost the insulin response to glucose; beta-cell insulin content was reduced by about 70%, and the proportion of proinsulin-related peptides increased from 18% to 38%. In the in vivo situation, pancreatic extracts from nonfasted diabetic Psammomys contained 36% proinsulin-related peptides in contrast to 15% in pancreatic extracts from nondiabetic animals. Thus, prolonged in vitro exposure of prediabetic Psammomys islets to high levels of glucose could reproduce the modified beta-cell secretory profiles observed in vivo in the diabetic animal. These results support the hypothesis that hyperproinsulinemia in NIDDM is secondary to the inability of beta-cells to meet a sustained increase in insulin demand, whereas individuals with normal beta-cells may meet such demand with an adequate output of mature insulin.
DEXAMETHASONE SUSTAINED DRUG DELIVERY IMPLANT FOR THE TREATMENT OF SEVERE UVEITIS (2000)

From the Departments of Ophthalmology, *Duke University, Durham, North Carolina, †University of Kentucky, Lexington, and ‡Tufts New England Medical Center, Boston, Massachusetts. Supported by NIH Grant EY09106 (Dr. Jaffe), the Adler Foundation (Dr. Jaffe), and Research to Prevent Blindness, Inc. Dr. Jaffe is a Lew R. Wasserman Merit Award Recipient. Drs. Pearson and Ashton have applied for a patent on the dexamethasone sustained drug delivery device and, as such, may have a financial interest in it. Correspondence: Glenn J. Jaffe, MD, Duke University Eye Center, Duke University, Box 3802, Durham, NC 27710; e-mail: [email protected] RETINA,TMThe Journal of Retinal and Vitreous Diseases, encourages authors to submit Brief Reports describing unusual findings, new techniques, and new instruments. Material submitted for consideration in this section of the journal is done so with the assumption that the data provided do not duplicate previously published material and that the material has not been submitted for consideration elsewhere. Each author must sign a disclosure to this effect (see Instructions to Authors for complete wording of transfer letter). Brief Reports submitted for this section of the journal may be subjected to the standard review process that is applied to other material submitted to RETINA. Brief Reports should follow the requirements listed in the Instructions to Authors, with the following caveats: Brief Reports should not exceed 4 pages in length; no more than 5 references should be cited; and each Brief Report should include no more than 4 figures.
High-Tc Phase Promoted and Stabilized in the Bi, Pb-Sr-Ca-Cu-O System (1988)

Partial substitution of Pb for Bi in the Bi-Sr-Ca-Cu-O system has been found to sharply increase the volume fraction of the high- T c phase when both the starting material (coprecipitated oxalate being used in the present study) and the heating process are appropriate. The sharp powder X-ray diffraction pattern obtained from well-grown particles, 5∼10 µm wide and 0.5 µm thick typically, was assigned to an orthorhombic cell with a =0.537 nm, b =2.682 nm, and c =3.726 nm. The electrical resistance dropped to zero at 107 K within the experimental limit of 10 -6 Ω. A large diamagnetic response in the ac susceptibility due to the Meissner effect was seen below 120 K. The dominance of the high- T c phase over the low- T c phase was roughly estimated at 9/1 in volume.
Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning (2002)

Aldose reductase (AR), a member of the aldo-keto reductase superfamily, has been shown to metabolize toxic aldehydes generated by lipid peroxidation, suggesting that it may serve as an antioxidant defense. To investigate its role in the late phase of ischemic preconditioning (PC), conscious rabbits underwent 6 cycles of 4-minute coronary occlusion/4-minute reperfusion. Twenty-four hours later, there was a marked increase in AR protein and activity and in the myocardial content of sorbitol, a unique product of AR catalysis. Pretreatment with N(omega)-nitro-L-arginine, a nitric oxide synthase inhibitor, or chelerythrine, a protein kinase C inhibitor (both given at doses that block late PC in this model), prevented the increase in AR protein 24 hours later, demonstrating that ischemic PC upregulates AR via nitric oxide- and protein kinase C-dependent signaling pathways. The AR-selective inhibitors tolrestat and sorbinil prevented AR-mediated accumulation of sorbitol and abrogated the infarct-sparing effect of late PC, demonstrating that enhanced AR activity is necessary for this cardioprotective phenomenon to occur. Inhibition of AR did not affect infarct size or the myocardial accumulation of the lipid peroxidation product 4-hydroxy trans-2-nonenal (HNE) in nonpreconditioned rabbits. The accumulation of HNE was inhibited by late PC, and this effect was abrogated by sorbinil. Taken together, these results establish AR as an essential mediator of late PC. Furthermore, the data suggest that myocardial ischemia/reperfusion injury is due in part to the generation of lipid peroxidation products and that late PC diminishes this source of injury by upregulating AR.