gebhart/patrepeval huggingface dataset:
Gold Nanoparticles: Interesting Optical Properties and Recent Applications in Cancer Diagnostics and Therapy (2007)

Recent years have seen tremendous progress in the design and study of nanomaterials geared towards biological and biomedical applications, most notable among these being the noble metal nanoparticles. In this review, we outline the surface-plasmon resonance-enhanced optical properties of colloidal gold nanoparticles directed towards recent biomedical applications with an emphasis on cancer diagnostics and therapeutics. Methods of molecular-specific diagnostics/detection of cancer, including strongly enhanced surface plasmon resonance light-scattering, surface-enhanced emission of gold nanorods and surface-enhanced Raman scattering, are described. We also discuss the plasmonic photothermal therapy of cancer achieved by using the strongly enhanced surface-plasmon resonance absorption of gold nanospheres and nanorods.
BCL-6 in the Pathogenesis of Non-Hodgkin's Lymphoma (2000)

(2000). BCL-6 in the Pathogenesis of Non-Hodgkin's Lymphoma. Cancer Investigation: Vol. 18, No. 4, pp. 356-365.
Disposition of intravenous and oral cyclosporine after administration with grapefruit juice* (1995)

The lack of effect on systemic clearance after intravenous cyclosporine suggests that grapefruit juice improves oral bioavailability by increasing absorption or reducing gut wall metabolism. The latter is more likely in view of studies that suggest significant gut wall metabolism of cyclosporine by CYP3A enzymes known to be inhibited by components of grapefruit juice.
Image‐guided and ‐monitored renal artery stenting using only MRI (2006)

This study has clearly demonstrated the first successful treatment of renal artery stenting in an experimental animal model solely under MRI guidance and monitoring.
DNA-Catalyzed Polymerization (2002)

Native DNA oligomers are shown to be stereoselective catalysts for the polymerization of 5'-amino-3'-acetaldehyde-modified thymidine/adenosine nucleosides through reductive amination. The reaction follows step-growth kinetics to read the encoded sequence and chain-length information in the antiparallel direction. Single mismatches in the template are selected against at a level of >100:1. A method is therefore established to translate biopolymer-encoded information stereoselectively into sequence- and chain-length specific synthetic polymers.
Efficacy Studies with Three Formulations of Cambendazole in Horses (1975)

Treatment with 3 formulations of cambendazole (paste, pellets, and suspension) was compared with thiabendazole treatment in 181 Quarter Horses (females and intact and altered males) of different ages in 2 experiments. The mean output of strongyle eggs, as measured by eggs per gram of feces (epg), was reduced by at least 95% by the 3 formulations of cambendazole compared with pretreatment epg and epg in simultaneously nonmedicated horses. Eggs of Parascaris equorum were seen in 19 of the younger horses in experiment I. Parascaris eggs were not seen in postmedication fecal samples from 14 horses treated wtih cambendazole. Of the 5 horses treated with thiabendazole, 2 had postmedication Parascaris egg counts.
Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma (2014)

Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).
Contrast Sensitivity of the Human Eye and Its Effects on Image Quality (1999)

Modulation Threshold and Noise Model for the Spatial Contrast Sensitivity of the Eye Extension of the Contrast Sensitivity Model to Extra-Foveal Vision Extension of the Contrast Sensitivity Model to the Temporal Domain Effect of Nonwhite Spatial Noise on Contrast Sensitivity Contrast Discrimination Model Image Quality Measure Effect of Various Parameters on Image Quality.
Analysis of direct and inverted DJH rearrangements in a human Ig heavy chain transgenic minilocus. (1995)

D to JH rearrangement can occur either by a deletional or an inversional mechanism. In this study, we have analyzed deletional and inversional D to JH recombination in a human Ig heavy chain transgenic minilocus. The analysis of these events in a transgenic minilocus rather than in vivo in the human is simplified by the presence of a limited number of well defined VH, D, and JH gene segments in the minilocus. We show that in the transgenic minilocus, all D gene segments can be rearranged by deletion and virtually all can be rearranged by inversion. We also show that depending upon the D gene segment, rearrangement by deletion occurs approximately 1 to 1000 times more frequently than rearrangement by inversion. Our data suggest that in vivo, signal and coding end sequences are the major influences on the rearrangement frequency of a particular gene segment in a given orientation rather than its position within the transgenic locus. Additionally, our data indicate that intronic and recombination signal sequences are involved in the bias for deletion over inversion rather than the recombinase machinery itself.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy (1994)

These data suggest relatively high 10-year rates of incidence and progression of retinopathy, and despite changes in the treatment of diabetes, there has been little change in the incidence and progression of diabetic retinopathy during the 10-year study period.
Tork: Conformational analysis method for molecules and complexes (2003)

A conformational search method for organic molecules and bimolecular complexes is presented. The method, termed Tork, uses normal-mode analysis in bond-angle-torsion coordinates and focuses on a key subset of torsional coordinates to identify natural molecular motions that lead the initial conformation to new energy minima. New conformations are generated via distortion along these modes and their pairwise combinations, followed by energy minimization. For complexes, special treatment is accorded to the six coordinates that specify the position and orientation of one molecule relative to the other. Tests described here show that Tork is highly efficient for cyclic, acyclic, and mixed single molecules, as well as for host-guest complexes.
Phase I/IB Study of Immunization with Autologous Tumor Cells Transfected with the GM-CSF Gene by Particle-Mediated Transfer in Patients with Melanoma or Sarcoma University of Wisconsin, Madison, Wisconsin (1997)

SCIENTIFIC ABSTRACT Phase I/IB Study of Immunization with Autologous Tumor Cells Transfected with The GM-CSF Gene by Particle-Mediated Transfer in Patients with Melanoma or Sarcoma The objective of this Phase I study is to assess the acute and long-term toxicities of intradermal vaccination of cancer patients with lethally-irradiated tumor cells that have been transfected by particle-mediated gene transfer (PMGT) with gold particles coated with human granulocyte-macrophage colony stimulating factor (GM-CSF) DNA in a plasmid expression vector. The GM-CSF DNA-coated gold particles are delivered to tumor cells using helium pressure with a hand held gene delivery device. Preclinical studies have demonstrated that vaccination of mice with irradiated, GM-CSF-transfected melanoma cells provided protection from subsequent challenges with non-irradiated, non-transfected tumor cells. Ongoing human tumor immunotherapy studies use patients' melanoma or renal carcinoma cells transfected with a retroviral vector containing GM-CSF cDNA as a vaccine to elicit anti-tumor immune responses. PMGT transfection, unlike retroviral transfection, does not require tumor cells to proliferate in vitro to undergo gene transfer. Instead, tumor tissue can be dissociated into small tissue clumps or cell aggregates and then immediately transfected using the gene gun. PMGT physically inserts the DNA without the need for cell surface interaction with viral components or exposure of the patient to viral antigens. As described in this protocol, fresh human sarcoma and melanoma specimens can be transfected with the GM-CSF DNA-coated gold particles with subsequent production of biologically active GM-CSF protein. In this study tumor tissue will be obtained from patients with melanoma or sarcoma. Tumor tissue will be dissociated, irradiated, and transfected with GM-CSF DNA by PMGT. In this ascending dosage study, two dose levels of GM-CSF DNA will be studied in 2 groups of 6 patients each. Patients will receive two intradermal injections of the irradiated, transfected tumor in a single extremity. On days 3 and 14 post-vaccination, patients will undergo surgical excision of the vaccination sites to assess GM-CSF production and infiltration of immune effector cells. On Day 25, patients will undergo DTH testing with intradermal injection in their opposite extremity of 5 × 106 irradiated non-transfected autologous tumor cells cryopreserved at the time of vaccine preparation. This injection site will be assessed on day 28 post-vaccination and surgical excision of the DTH testing site will be performed on day 28 if a positive reaction is noted. The patients will be observed for local and systemic toxicity on days 2, 3, 5, 8, 14, 25, and 28 after the vaccination. Restaging of the patients' disease and long term toxicity evaluation will be performed at 3, 6, and 12 months and then yearly.
The cytokine interleukin 21: a new player in coeliac disease? (2008)

In this issue of Gut ,1 Fina et al demonstrate that interleukin 21 (IL21) expression is increased in the intestinal mucosa of patients with active coeliac disease (CD) but not that of treated patients ( see page 887 ). The authors show that IL21 is produced by CD4+ lamina propria T cells, a finding consistent with previous work indicating that this cytokine is exclusively produced by CD4+ T cells. Using a neutralising anti-IL21 antibody, they observed that blocking IL21 activity reduced the increase in interferon γ mRNA induced by gliadin digests in intestinal organ cultures from treated CD patients. Since the anti-IL21 antibody also reduced the induction of mRNA for T-bet, the transcription factor that controls the differentiation of interferon γ-producing CD4+ T lymphocytes (so-called T helper cell type 1 or Th1 lymphocytes), the authors conclude that IL21 is an important contributor to the mucosal Th1 proinflammatory response.1 The mucosal Th1 response in CD is generally ascribed to lamina propria CD4+ T cells that recognise gluten peptides presented by the human leucocyte antigen (HLA)-DQ2/8 molecules at the surface of mucosal dendritic cells. This response accounts for the interplay between the major genetic risk factor, the MHC (major histocompatibility complex) class II genes encoding the HLA-DQ2/8 molecules, and the triggering environmental factor gluten, and is considered instrumental in the pathogenesis of CD enteropathy.2

These results are of particular interest following the first genome-wide association study recently carried out in CD by van Heel et al .3 The latter study has indeed provided convincing evidence that the chromosomal 4q27 region harbouring the genes encoding the IL2 and IL21 cytokines might be involved in CD. In this study based on the use of single-nucleotide polymorphisms (SNPs), several variants were highly significant when analysed in three distinct populations of UK, Dutch and …
Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome (1997)

We have developed a system for site-specific DNA integration in human cells, mediated by the adeno-associated virus (AAV) Rep proteins. In its normal lysogenic cycle, AAV integrates at a site on human chromosome 19 termed AAVS1. We describe a rapid PCR assay for the detection of integration events at AAVS1 in whole populations of cells. Using this assay, we determined that the AAV Rep proteins, delivered in cis or trans, are required for integration at AAVS1. Only the large forms of the Rep protein, Rep78 and Rep68, promoted site-specific integration. The AAV inverted terminal repeats, present in cis, were not essential for integration at AAVS1, but in cells containing Rep, they increased the efficiency of integration. In the presence of the Rep proteins, the integration of a plasmid containing AAV inverted terminal repeats occurred at high frequency, such that clones containing the plasmid could be isolated without selection. In two of the five clones analyzed by fluorescence in situ hybridization, the plasmid DNA was integrated at AAVS1. In most of the clones, at least one copy of the entire plasmid was integrated in a tandem array. Detailed analysis of the integrated plasmid structure in one clone suggested a complex mechanism producing rearrangements of the flanking genomic DNA, similar to those observed with wild-type AAV.
Engineering T-cells with antibody-based chimeric receptors for effective cancer therapy. (2005)

The combination of power and specificity inherent within the immune system make its manipulation an attractive prospect for the development of novel anticancer therapies. However, tumors are frequently poorly recognized by the immune system, and intrinsic controls limit the benefit from active immunization. These and other issues have proved major challenges in the search for effective cancer immunotherapy. Recent advances in the understanding of the immune system and the development of methods to manipulate it have led to the point where engineered T-cell therapy can be tested in the clinical setting with a realistic chance of success. These advances are considered and potential future clinical and scientific issues involved in the successful development of effective, engineered T-cell therapy are examined.
Comparison of Seal Oil to Tuna Oil on Plasma Lipid Levels and Blood Pressure in Hypertriglyceridaemic Subjects (2009)

As meat is a rich source of the omega-3 fatty acid docosapentaenoic acid (DPA) and Australians consume six times more meat than fish, investigation of the potential health benefit of DPA is warranted. The aims were to compare the effects of seal oil supplementation with fish oil, on measures of plasma lipids and blood pressure in hypertriglyceridaemic subjects. Forty-eight volunteers were recruited from the Wollongong community and were randomly allocated to one of three groups either receiving 1 g/day of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) using one of three oils: seal oil capsules (340 mg eicosapentaenoic acid (EPA), 230 mg DPA, 450 mg DHA), fish oil capsules (210 mg EPA, 30 mg DPA, 810 mg DHA) or placebo capsules (containing sunola oil) for 6 weeks. Plasma triglycerides remained unchanged in the placebo group, whilst reductions of 7 and 14% (P < 0.05) were seen in the fish oil and seal oil groups respectively. Systolic blood pressure improved by 8 and 5 mmHg with seal oil and fish oil respectively (P < 0.05). The mean arterial pressure was significantly lower after seal oil supplementation (P < 0.005) compared with the placebo group. These results indicate that seal oil is as effective as fish oil in lowering plasma triglycerides and blood pressure.
A scientific visualization workbench (2003)

A system for visualization of data from supercomputer simulations has been developed. The scientific visualization workbench, as it is called, is based on an industry standard workstation (a Sun 3/160C), the NeWS window system, and a video/graphics add-in card, which is supported by NeWS. Also involved is a frame buffer attached to a 48-Mb/s Cray channel and a video link from the frame buffer to the Sun workstation. Computation and graphics preparation are performed on the Cray under the control of a NeWS client program. Images are rasterized and sent to the workstation at the rate of 25 frame/s. The workbench permits the scientist to converse with applications running on a Cray but still retain the convenience and flexibility of a personal workstation environment. The video link allows animated graphics images to be displayed on the workstation at a much higher rate than would be possible with a conventional network connection, i.e. Ethernet. Also, NeWS affords the convenience of a modern window system. Live video can be displayed in a window anywhere on the screen, while other windows may contain conventional text or graphics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Recognition of chylomicron remnants and β-migrating very-low-density lipoproteins by the remnant receptor of parenchymal liver cells is distinct from the liver α2-macroglobulin-recognition site (1991)

The uptake in vivo of chylomicrons and beta-migrating very-low-density lipoprotein (beta-VLDL) by rat liver, which is primarily carried out by parenchymal cells, is inhibited, 5 min after injection, to respectively 35 and 8% of the control values after preinjection of lactoferrin. The decrease in the uptake of lipoproteins by the liver caused by lactoferrin is a specific inhibition of uptake by parenchymal cells. Competition studies in vitro demonstrate that chylomicron remnants and beta-VLDL compete for the same recognition site on parenchymal cells. Data obtained in vivo together with the competition studies performed in vitro indicate that chylomicron remnants and beta-VLDL interact specifically with the same remnant receptor. Hepatic uptake of 125I-labelled-alpha 2-macroglobulin in vivo, mediated equally by parenchymal and endothelial cells, is not decreased by preinjection of lactoferrin and no effect on the parenchymal-cell-mediated uptake is found. In vitro, alpha 2-macroglobulin and chylomicron remnants or beta-VLDL show no cross-competition. Culturing of parenchymal cells for 24-48 h leads to a decrease in the cell association of alpha 2-macroglobulin to 26% of the initial value, while the cell association of beta-VLDL with the remnant receptor is not influenced. It is concluded that beta-VLDL and chylomicron remnants are recognized by a specific remnant receptor on parenchymal liver cells, while uptake of alpha 2-macroglobulin by liver is carried out by a specific receptor system (presumably involving the LDL-receptor-related protein) which shows properties that are distinct from those of the remnant receptor.
Combining metabolic and protein engineering of a terpenoid biosynthetic pathway for overproduction and selectivity control (2010)

A common strategy of metabolic engineering is to increase the endogenous supply of precursor metabolites to improve pathway productivity. The ability to further enhance heterologous production of a desired compound may be limited by the inherent capacity of the imported pathway to accommodate high precursor supply. Here, we present engineered diterpenoid biosynthesis as a case where insufficient downstream pathway capacity limits high-level levopimaradiene production in Escherichia coli. To increase levopimaradiene synthesis, we amplified the flux toward isopentenyl diphosphate and dimethylallyl diphosphate precursors and reprogrammed the rate-limiting downstream pathway by generating combinatorial mutations in geranylgeranyl diphosphate synthase and levopimaradiene synthase. The mutant library contained pathway variants that not only increased diterpenoid production but also tuned the selectivity toward levopimaradiene. The most productive pathway, combining precursor flux amplification and mutant synthases, conferred approximately 2,600-fold increase in levopimaradiene levels. A maximum titer of approximately 700 mg/L was subsequently obtained by cultivation in a bench-scale bioreactor. The present study highlights the importance of engineering proteins along with pathways as a key strategy in achieving microbial biosynthesis and overproduction of pharmaceutical and chemical products.
A novel enzyme from bovine neurointermediate pituitary catalyzes dealkylation of .alpha.-hydroxyglycine derivatives, thereby functioning sequentially with peptidylglycine .alpha.-amidating monooxygenase in peptide amidation (1990)

We report here the isolation of a novel enzyme from bovine neurointermediate pituitary which catalyzes the conversion of alpha-hydroxybenzoylglycine to benzamide. This enzyme, termed HGAD (alpha-hydroxyglycine amidating dealkylase), is a soluble protein with an apparent molecular mass of 45 kDa and no apparent cofactor requirement. Addition of HGAD to purified neurointermediate pituitary PAM (peptidylglycine alpha-amidating monooxygenase, EC 1.14.17.3) increases the rate of formation of amide products by an order of magnitude. Sequential additions of PAM and HGAD gave results consistent with PAM first catalyzing the formation of an intermediate that is subsequently, in a separate reaction, converted by HGAD to the final amide product. Experiments with olefinic inactivators demonstrate that HGAD is not required for turnover-dependent inactivation of PAM and, correspondingly, that HGAD activity is not affected by inactivators of PAM. As expected, HGAD has no effect on the rate of PAM-catalyzed sulfoxidation, where a reaction analogous to that occurring during amidation of glycine-extended substrates is not possible. On the basis of these results, we propose that peptide C-terminal amidation in neurointermediate pituitary is a two-step process, with PAM first catalyzing the conversion of a glycine-extended peptide to the alpha-hydroxyglycine derivative, which is in turn converted to the final amide product by HGAD.
Venous and arterial thrombosis: a continuous spectrum of the same disease? (2004)

This editorial refers to ‘A prospective study on cardiovascular events after acute pulmonary embolism’† by C. Becattini et al. , on page 77 

Over 150 years ago, Virchow1 first postulated that a triad of conditions predispose to thrombus formation, these three factors being abnormalities in the vessel wall, blood flow, and the coagulability of blood. The first two components of Rudolf Virchow's triad were based on his meticulous necropsy observations; the third reflects Virchow's remarkable insight that is only today, 150 years later, being substantiated at a molecular level. While Virchow was referring to venous thrombosis, the same processes have been applied to arterial thrombosis. A contemporary viewpoint of Virchow's triad should consider: inflammation, endothelial dysfunction, and atherosclerosis (i.e. abnormal vessel wall), abnormalities of haemorheology and turbulence at bifurcations and stenotic regions (i.e. abnormal blood flow), and finally, abnormalities in platelet function, coagulation, fibrinolysis, and metabolic or hormonal factors (i.e. abnormal blood constituents).1,2

In Virchow's triad of the twenty-first century, endothelial dysfunction emerges as the most important component. The vascular endothelium influences not only the three classically interacting components of haemostasis, but also the natural sequelae of endothelial dysfunction: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, which are best defined as an anti- and a pro-thrombotic state. The vascular endothelial cell surface is possibly the major site of control of these coagulant and anticoagulant interactions.3 Under physiological conditions, endothelium mediates vascular vasodilatation, prevents platelet adhesion and activation, blocks thrombin formation, and mitigates fibrin deposition through several pathways. … 

*Av. San Angel 130, Depto 5, Col. Valle de San Angel, CP 66290, Garza Garcia, NL, Mexico. Tel/fax: +52 81 83031641. E-mail address : jerjes{at}infosel.net.mx
Optical Mapping in a New Guinea Pig Model of Ventricular Tachycardia Reveals Mechanisms for Multiple Wavelengths in a Single Reentrant Circuit (1996)

We provide direct experimental evidence that multiple wavelengths are present even within a relatively simple reentrant circuit. Abrupt changes in loading during wave-front pivoting, rather than membrane ionic properties or fiber structure, were a major determinant of lambda and, therefore, may play an important role in the stability of reentry.
Acne treatment with a 1,450 nm wavelength laser and cryogen spray cooling (2002)

The studies reported here demonstrate the feasibility of treating acne using a photothermal approach with a mid-IR laser and cryogen cooling.