gebhart/patrepeval huggingface dataset:
Plant terpenoid synthases: Molecular biology and phylogenetic analysis (1998)

This review focuses on the monoterpene, sesquiterpene, and diterpene synthases of plant origin that use the corresponding C10, C15, and C20 prenyl diphosphates as substrates to generate the enormous diversity of carbon skeletons characteristic of the terpenoid family of natural products. A description of the enzymology and mechanism of terpenoid cyclization is followed by a discussion of molecular cloning and heterologous expression of terpenoid synthases. Sequence relatedness and phylogenetic reconstruction, based on 33 members of the Tps gene family, are delineated, and comparison of important structural features of these enzymes is provided. The review concludes with an overview of the organization and regulation of terpenoid metabolism, and of the biotechnological applications of terpenoid synthase genes.
Biomarkers in systemic lupus erythematosus: challenges and prospects for the future (2013)

The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions.
High-frequency permeability of laminated and unlaminated, narrow, thin-film magnetic stripes (invited) (1991)

The permeability of the magnetic material in a thin-film magnetic head is an important, but hard to characterize, parameter since the magnetic permeability depends on the head domain structure, the drive frequency, and the shape and size of the head. We have measured the high-frequency permeability from 1 MHz to 300 MHz, hysteresis loops, and domain structure of unlaminated and multilayer magnetic thin-films as a function of stripe width for arrays of long narrow stripes. Monolithic permalloy films and permalloy films laminated with SiO2 have been photolithographically patterned and ion-milled to create 3 to 1000 μm wide rectangles, 1 cm long, with the hard axis oriented along the long axis of the rectangles. The high-frequency permeability of each array of a given width is measured by the signal detected by a nonresonant butterfly-coil pickup loop when the film is driven by a uniform radio-frequency magnetic field generated by a strip-line waveguide. The changes in domain pattern as the film structure and stripe width are varied are observed with a Kerr-effect imaging microscope. In unlaminated films, which exhibit standard closure domains, a reduction in high-frequency permeability is observed in agreement with simple models when the closure domains become a significant fraction of the film area. In laminated films with thick magnetic layers, the transition from the laminated domain state to closure domains as the stripe width is decreased occurs where expected from straightforward energy arguments. However, for magnetic layers less than 1 μm thick, where a transition from the easy-axis laminated domain state to a uniform hard-axis state is expected as the stripe width is reduced, the films first change from the easy-axis state to a complicated, low-Kerr-contrast domain pattern before switching to the hard-axis state at much larger widths than predicted. While the laminated state and hard-axis permeabilities are frequency independent, the permeability of the intermediate state rolls off beginning at between 10 and 100 MHz. For still thinner magnetic layers (250 Å), the multilayer retains the high-permeability easy-axis laminated domain state to the narrowest width measured, 3 μm.
Intra-arterial Chemotherapy for the Management of Retinoblastoma (2011)

Our experience suggests that intra-arterial chemotherapy is safe and effective in the treatment of advanced intraocular retinoblastoma.
Scalable Light-Induced Metal to Semiconductor Conversion of Carbon Nanotubes (2009)

Coexistence of metallic and semiconducting carbon nanotubes in as-grown samples sets important limits to their application in high-performance electronics. We present the metal-to-semiconductor conversion of carbon nanotubes for field-effect transistors based on both aligned nanotubes and individual nanotube devices. The conversion process is induced by light irradiation, scalable to wafer-size scales and capable of yielding improvements in the channel-current on/off ratio up to 5 orders of magnitude in nanotube-based field-effect transistors. Inactivation of metallic nanotubes in the channels was achieved as a consequence of a diameter-dependent photochemical process that led to a controlled oxidation of the nanotube sidewall and, hence, stronger localization of pi-electrons. Optimization of irradiation conditions yields nearly 90% of depletable nanotube field-effect transistors.
Deriving the Glutamate Clearance Time Course from Transporter Currents in CA1 Hippocampal Astrocytes: Transmitter Uptake Gets Faster during Development (2005)

At many excitatory synapses, the neurotransmitter glutamate diffuses beyond the synaptic cleft to activate extrasynaptic targets. The extent and impact of such transmitter "spillover" on the processing capacity of neuronal networks are unclear, in part because it remains unknown how far transmitter diffuses from its point of release before being removed from the extracellular space by high-affinity glutamate transporters. Synaptically activated, transporter-mediated currents (STCs) recorded in hippocampal astrocytes provide an experimental measure of glutamate uptake, but the time course of the STC may be shaped, or "filtered," by other factors and therefore not represent a direct indication of clearance rate. Here, STCs were recorded from astrocytes in rat hippocampal slices under conditions in which uptake capacity was reduced and the STC decay reflected a slowed rate of glutamate clearance. The temporal characteristics of the filtering mechanisms were extracted from these responses, and the glutamate clearance time course in control conditions was derived. The results indicate that glutamate can be cleared from the extrasynaptic space within 1 ms. Clearance is fastest in adult neuropil, corresponding to a developmental increase in glial transporter expression. Synaptically released glutamate is taken up at the same rate as glutamate released via flash photolysis, indicating that the spatial location of transporters relative to the site of glutamate release does not affect the time course of clearance. Slower clearance in young animals would permit glutamate to diffuse greater distances, indicating a particularly important role for extrasynaptic receptors early in development.
Immune responses to osteochondral allografts. Current knowledge and future directions. (1983)

Immune responses directed against osteochondral allograft-associated immunogens have been demonstrated in a variety of animals models and, to a more limited degree, in human recipients. The most extensively studied, and presumably the most potent source of sensitization, are cell-surface transplantations found on the heterogeneous cell types ubiquitous to skeletal tissues. By virtually all criteria used for evaluation, the immunogenicity resulting from histocompatibility antigens is reduced by deep-freezing the allograft prior to implantation, and responses are diminished even further when tissues are freeze-dried. There is preliminary evidence to suggest that matrix components, particularly proteoglycan subunits, are also capable of sensitizing osteochondral graft recipients. The magnitude and significance of these immunogens are matters of speculation. Collagen may also act as an osteochondral allograft immunogen. The significance of osteochondral allograft immunogenicity, as compared with biomechanical factors in the incorporation of a bone graft, has not yet been elucidated. The effect of immune responses on clinical allograft success, if it is as important as it appears, should profoundly influence future osteochondral allograft research in reconstructive joint surgery.
A selective model to suppress NLOS signals in angle-of-arrival (AOA) location estimation (2002)

Angle-of-arrival (AOA) is a key technique in wireless location estimation. The study of AOA becomes very important with the FCC ruling regarding the wireless Enhanced 911 (E911) emergency calling systems. This paper studies the performance of AOA in a cellular environment. Special attention is drawn to the non-line-of-sight (NLOS) problem that is a significant error source in position estimation. A model is proposed to identify and to reduce the NLOS errors with the coordination of many base stations. The simulation results show that the proposed algorithm is quite efficient in reducing the estimation error when NLOS is present.
Comparison of the effect of native glucagon‐like peptide 1 and dipeptidyl peptidase IV‐resistant analogues on insulin release from rat pancreatic islets (1999)

The analogues tested are biologically active and resistant to degradation by dipeptidyl peptidase IV. Their greater metabolic stability may help to realize the potential of GLP-1 analogues in diabetes therapy.
Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase (2005)

Human serotonin [5-hydroxytryptamine (5-HT)] transporters (hSERT, 5HTT, and SLC6A4) inactivate 5-HT after release and are prominent targets for therapeutic intervention in mood, anxiety, and obsessive-compulsive disorders. Multiple hSERT coding variants have been identified, although to date no comprehensive functional analysis of these variants has been reported. We transfected hSERT or 10 hSERT coding variants and examined total and surface protein expression, antagonist recognition, and transporter modulation by posttranslational, regulatory pathways. Two variants, Pro339Leu and Ile425Val, demonstrated significant changes in surface expression supporting alterations in 5-HT transport capacity (V(max)). Regardless of basal transport activity, all SERT variants displayed a capacity for rapid, phorbol ester-triggered down-regulation. Remarkably, five variants (Thr4Ala, Gly56Ala, Glu215Lys, Lys605Asn, and Pro612Ser) demonstrated no capacity for 5-HT uptake stimulation after acute protein kinase G (PKG)/p38 mitogen-activated protein kinase (MAPK) activation. Epstein-Barr virus (EBV)-transformed lymphocytes natively expressing the most common of these variants (Gly56Ala) exhibited a similar loss of 5-HT uptake stimulation by PKG/p38 MAPK activators. HeLa cells transfected with the Gly56Ala variant demonstrated elevated basal phosphorylation and, unlike hSERT, could not be further phosphorylated after 8-bromo cGMP (8BrcGMP) treatments. These studies reveal cellular phenotypes associated with naturally occurring human SERT coding variants and suggest that altered transporter regulation by means of PKG/p38 MAPK-linked pathways may influence risk for disorders attributed to compromised 5-HT signaling.
Chemical chaperones protect from effects of apoptosis-inducing mutation in carbonic anhydrase IV identified in retinitis pigmentosa 17 (2004)

Carbonic anhydrase (CA) IV is a glycosylphosphotidylinositol-anchored enzyme highly expressed on the plasma face of microcapillaries and especially strongly expressed in the choriocapillaris of the human eye. In collaboration with scientists at the University of Cape Town (Rondebosch, South Africa), we recently showed that the R14W mutation in the signal sequence of CA IV, which they identified in patients with the retinitis pigmentosa (RP) 17 form of autosomal dominant RP, results in accumulation of unfolded protein in the endoplasmic reticulum (ER), leading to ER stress, the unfolded protein response, and apoptosis in a large fraction of transfected COS-7 cells expressing mutant, but not wild-type, CA IV. Here we present experiments showing that several well characterized CA inhibitors largely prevent the adverse effects of expressing R14W CA IV in transfected COS-7 cells. Specifically, CA inhibitors prevent the accelerated turnover of the mutant protein, the up-regulation of Ig-binding protein, double-stranded RNA-regulated protein kinase-like ER kinase, and CCAAT/enhancer-binding protein homologous protein (markers of the unfolded protein response and ER stress), the inhibition of production of other secretory proteins expressed from COS-7-transfecting plasmids, and the induction of apoptosis, all characteristics of transfected cells expressing R14W CA IV. Furthermore, treatment with 4-phenylbutyric acid, a nonspecific chemical chaperone used in other protein-folding disorders, also dramatically reduces the apoptosis-inducing effect of expressing R14W CA IV cDNA in transfected COS-7 cells. These experiments suggest a promising approach to treatment of RP17 that might delay the onset or possibly prevent this autosomal dominant form of RP.
Minimal antigenicity of intron A in human recipients demonstrated by three analytical methods. (1988)

Antibodies to recombinant human interferon alpha 2b (Intron A) were detected in only a small number of 101 Intron A recipients. This group of cancer patients received Intron A for a mean treatment time of 4.3 months and were selected from disease categories in which subjects were expected to be immunocompetent. Three methods for the detection of antibodies were employed: (a) a bioassay measuring the neutralizing activity of the sera for the antiviral action of interferon alpha 2b, (b) a radioimmunological assay measuring the ability of the sera to prevent the detection of interferon alpha 2b by an immunoradiometric assay (IRMA), and (c) an enzyme-linked immunosorbent assay (ELISA) that measures the binding of immunoglobulins to interferon alpha 2b attached to a solid support. Three of the 101 patients developed neutralizing activity during treatment. Two of these exhibited low neutralizing titers of 1:6-1:9 and were unreactive in the IRMA and ELISA, while only one was positive by bioassay, IRMA, and ELISA. An additional seven patients were positive only in the ELISA. Six of these were borderline positive, i.e., the posttreatment:pretreatment ratio was less than or equal to 5. The results of this study confirm that Intron A is minimally antigenic in human subjects.
Scheimpflug and high-resolution magnetic resonance imaging of the anterior segment: a comparative study (2004)

In a recent paper, Koretz et al. [J. Opt. Soc. Am. A 21, 346 (2004)] conclude that the results of the "corrected Scheimpflug technique" to obtain the shape of the human lens differ significantly from their magnetic resonance imaging (MRI) data. We demonstrate that the conclusions are based on incorrect statistical methods. A straightforward statistical comparison shows that there is no significant difference between the corrected Scheimpflug results and the MRI data.
APT070 (Mirococept), a membrane‐localised complement inhibitor, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury (2005)

Activation of the complement system has been shown to play a major role in the mediation of reperfusion injury. Here, we assessed the effects of APT070 (Mirococept), a novel membrane-localised complement inhibitor based on a recombinant fragment of soluble CR1, on the local, remote and systemic injuries following intestinal ischaemia and reperfusion (I/R) in the rat. In a model of mild I/R injury (30 min of ischaemia and 30 min of reperfusion), APT070 dose-dependently (1-10 mg kg(-1)) inhibited the increase in vascular permeability of and neutrophil influx into intestine and lungs. Maximal inhibition occurred at 10 mg kg(-1). Following severe I/R injury (120 min of ischaemia and 120 min of reperfusion), APT070 (10 mg kg(-1)) markedly prevented neutrophil influx and the increase in vascular permeability both in the intestine and the lungs.APT070 also effectively suppressed the increase of tissue (intestine and lungs) and serum concentrations of TNF-alpha and IL-6, but not those of IL-1beta or IL-10. There was no significant reduction of mortality in the APT070 group. In conclusion, treatment with the membrane-targeted complement inhibitor APT070 significantly reduced the hyperinflammatory response after mild and severe ischaemia and reperfusion injury (I/RI) in rats. APT070 may be effective in therapeutic indications involving gut I/RI.
Inhibition of tissue factor activity reduces the density of cellular network formation in an in vitro model of angiogenesis (2002)

Tissue factor (TF) is a transmembrane glycoprotein that was originally recognized for its ability to initiate the extrinsic pathway of coagulation. More recently, additional functions of TF in cellular signalling have emerged, notably the role of TF in vasculogenesis and angiogenesis. We have described previously the ability of a peptide derived from the apolipoprotein B100 (apoB100) moiety of low-density lipoproteins (KRAD14) to inhibit the procoagulant function of TF. In this study, we demonstrate the ability of the KRAD14 peptide to attenuate the density of cellular network structures of T24 cells grown on specialized matrix (Matrigel). In addition, an alternative inhibitor of TF activity, the TF8 5G9 antibody, also reduces the density of cellular network formation. Targeted use of a stable structural equivalent of the KRAD14 peptide may thus prove useful in the prophylactic treatment of diseases whose pathologies feature the formation of neovascular tissue, e.g. tumour growth and metastasis, rupture of atherosclerotic plaques and retinopathy secondary to diabetes.
Validation of the Cardiosphere Method to Culture Cardiac Progenitor Cells from Myocardial Tissue (2009)

This study demonstrates that direct culture and expansion of CPCs from myocardial tissue is simple, straightforward, and reproducible when appropriate techniques are used.
Clinical spectrum and diagnosis of cobalamin deficiency [see comments] (1990)

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.
Understanding risk in hypercholesterolemia (2003)

Atherosclerosis was relatively uncommon 100 years ago, when researchers first established its link to elevated cholesterol. As the twentieth century progressed, however, factors such as high-fat diets, sedentary lifestyles, cigarette smoking, and urbanization combined to increase the prevalence of both hypercholesterolemia and coronary heart disease (CHD) throughout the developed world. Atherogenesis begins at an early age and progresses throughout life, and cholesterol levels during young adulthood strongly predict the risk of CHD and related mortality during the ensuing decades. The total cholesterol level in youth also determines the actual age at which a critical level of atherosclerosis will be reached. Early studies on the primary and secondary prevention of CHD failed to identify a linear relationship between lipid lowering and risk reduction, primarily because older lipid-lowering agents lacked the potency to reduce cholesterol levels significantly enough to achieve lower cardiovascular event and mortality rates. The introduction of the statins, with their powerful lipid-lowering activity, overcame this limitation. Several large-scale trials of statins firmly established the efficacy of these agents in both primary and secondary CHD prevention. With the availability of statin therapy, we are now able to reduce the risk of major adverse CHD events by an average of 30%, regardless of patient age or gender.
Total Cholesterol and High Density Lipoprotein Cholesterol as Important Predictors of Erectile Dysfunction (1994)

Although erectile dysfunction is frequently seen in patients with manifestations of arteriosclerotic disease, the independent contribution of serum cholesterol in predicting erectile dysfunction is unclear. The aim of this study was to examine the relation between serum cholesterol and erectile dysfunction. Medical histories, physical examinations, and blood tests were obtained at Cooper Clinic, Dallas, Texas, from 3,250 men aged 26-83 years (mean, 51 years) without erectile dysfunction at their first visit, who had one more clinic visit, all between 1987 and 1991. These men were followed 6-48 months after the first clinic visit (mean, 22 months). Erectile dysfunction was reported in 71 men (2.2%) during follow-up. Every mmol/liter of increase in total cholesterol was associated with 1.32 times the risk of erectile dysfunction (95% confidence interval 1.04-1.68), while every mmol/liter of increase in high density lipoprotein cholesterol was associated with 0.38 times the risk (95% confidence interval 0.18-0.80). Men with a high density lipoprotein cholesterol measurement over 1.55 mmol/liter (60 mg/dl) had 0.30 times the risk (95% confidence interval 0.09-1.03) as did men with less than 0.78 mmol/liter (30 mg/dl). Men with total cholesterol over 6.21 mmol/liter (240 mg/dl) had 1.83 times the risk (95% confidence interval 1.00-3.37) as did men with less than 4.65 mmol/liter (180 mg/dl). Those differences remained essentially unchanged after adjustment for other potential confounders. The authors conclude that a high level of total cholesterol and a low level of high density lipoprotein cholesterol are important risk factors for erectile dysfunction.