gebhart/patrepeval huggingface dataset:
Production of Aromatic Compounds by Metabolically Engineered Escherichia coli with an Expanded Shikimate Pathway (2012)

Escherichia coli was metabolically engineered by expanding the shikimate pathway to generate strains capable of producing six kinds of aromatic compounds, phenyllactic acid, 4-hydroxyphenyllactic acid, phenylacetic acid, 4-hydroxyphenylacetic acid, 2-phenylethanol, and 2-(4-hydroxyphenyl)ethanol, which are used in several fields of industries including pharmaceutical, agrochemical, antibiotic, flavor industries, etc. To generate strains that produce phenyllactic acid and 4-hydroxyphenyllactic acid, the lactate dehydrogenase gene (ldhA) from Cupriavidus necator was introduced into the chromosomes of phenylalanine and tyrosine overproducers, respectively. Both the phenylpyruvate decarboxylase gene (ipdC) from Azospirillum brasilense and the phenylacetaldehyde dehydrogenase gene (feaB) from E. coli were introduced into the chromosomes of phenylalanine and tyrosine overproducers to generate phenylacetic acid and 4-hydroxyphenylacetic acid producers, respectively, whereas ipdC and the alcohol dehydrogenase gene (adhC) from Lactobacillus brevis were introduced to generate 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol producers, respectively. Expression of the respective introduced genes was controlled by the T7 promoter. While generating the 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol producers, we found that produced phenylacetaldehyde and 4-hydroxyphenylacetaldehyde were automatically reduced to 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol by endogenous aldehyde reductases in E. coli encoded by the yqhD, yjgB, and yahK genes. Cointroduction and cooverexpression of each gene with ipdC in the phenylalanine and tyrosine overproducers enhanced the production of 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol from glucose. Introduction of the yahK gene yielded the most efficient production of both aromatic alcohols. During the production of 2-phenylethanol, 2-(4-hydroxyphenyl)ethanol, phenylacetic acid, and 4-hydroxyphenylacetic acid, accumulation of some by-products were observed. Deletion of feaB, pheA, and/or tyrA genes from the chromosomes of the constructed strains resulted in increased desired aromatic compounds with decreased by-products. Finally, each of the six constructed strains was able to successfully produce a different aromatic compound as a major product. We show here that six aromatic compounds are able to be produced from renewable resources without supplementing with expensive precursors.
Heterogeneity of sodium-dependent D-glucose transport sites along the proximal tubule: evidence from vesicle studies (1982)

The glucose transport properties of brush border membrane vesicles from the outer cortex (early proximal tubule) and outer medulla (late proximal tubule) of rabbit kidney were studied. In the outer cortical preparation the behavior of the sodium-dependent component of D-glucose flux indicated the presence of a low-affinity transport system with Km congruent to 6 mM and Vmax congruent to 10 nmol.min-1.mg protein-1 as measured under zero trans conditions at 40 mM NaCl and 17 degrees C. By contrast, in the outer medullary preparation this component of flux behaved as a high-affinity system with Km congruent to 0.35 mM and Vmax congruent to 4 nmol.min-1.mg protein-1. Differences in transport specificity between the two preparations were also indicated and glucose uptake by the outer cortical vesicles was significantly more sensitive to inhibition by phlorizin. These results suggest the existence of two distinct sodium-dependent D-glucose transport systems in the renal proximal tubule brush border membrane. The kinetic studies presented here were done under zero trans sodium and glucose conditions. The rationale and methodology for carrying out these measurements reliably are discussed in detail.
Structural Dynamics of the Cereblon Ligand Binding Domain (2015)

Cereblon, a primary target of thalidomide and its derivatives, has been characterized structurally from both bacteria and animals. Especially well studied is the thalidomide binding domain, CULT, which shows an invariable structure across different organisms and in complex with different ligands. Here, based on a series of crystal structures of a bacterial representative, we reveal the conformational flexibility and structural dynamics of this domain. In particular, we follow the unfolding of large fractions of the domain upon release of thalidomide in the crystalline state. Our results imply that a third of the domain, including the thalidomide binding pocket, only folds upon ligand binding. We further characterize the structural effect of the C-terminal truncation resulting from the mental-retardation linked R419X nonsense mutation in vitro and offer a mechanistic hypothesis for its irresponsiveness to thalidomide. At 1.2Å resolution, our data provide a view of thalidomide binding at atomic resolution.
Driving Schemes for a-Si and LTPS AMOLED Displays (2005)

Design of stable active matrix organic light-emitting diode (AMOLED) displays comes with significant challenges that stem from the electrical property of the backplane materials, line parasitics in the matrix, and the opto-electronic property of the organic light-emitting diode (OLED). This paper reviews voltage and current programming schemes for AMOLEDs. Following a systematic review of pixel circuits, design considerations are examined for both current and voltage schemes with focus on stability and programming speed for both amorphous silicon (a-Si) and low temperature polysilicon (LTPS) pixel circuits. In particular, spatial parameter variations and stability, which hinder reliable operation of AMOLED display backplanes, are discussed. Analysis shows that while driving schemes reported hitherto maybe suitable for small and medium size displays, new schemes are critically needed for large-area high-resolution AMOLED displays.
Thick-polysilicon-based surface micromachined capacitive accelerometer with force-feedback operation (1995)

This paper describes the concept, the design and measurement results of a surface micromachined accelerometer. For the accelerometer presented here a polysilicon high rate deposition process was used to fabricate polysilicon layers with a thickness of 10 micrometers . The sensor is designed as an interdigital finger structure forming a differential capacitor, where the moveable fingers are mounted on a moveable mass and the fixed electrodes are anchored on the substrate. The air gap between the fingers is 1 micrometers . A force-feedback operation mode is realized to increase the sensor performance. A two chip solution with sensing element and signal processing circuit on separate chips was chosen as first approach towards a monolithic integrated accelerometer. The evaluation circuit was realized in BiCMOS technology. Sensors with a closed-loop sensitivity of 8mV/g and a bandwidth of about 10kHz have been fabricated. A resolution of 0.1g and a linearity error of less than 1% could be achieved for a measurement range of +/- 100 g.
Application of a Novel Tool for Diagnosing Bile Acid Diarrhoea (2013)

Bile acid diarrhoea (BAD) is a common disease that requires expensive imaging to diagnose. We have tested the efficacy of a new method to identify BAD, based on the detection of differences in volatile organic compounds (VOC) in urine headspace of BAD vs. ulcerative colitis and healthy controls. A total of 110 patients were recruited; 23 with BAD, 42 with ulcerative colitis (UC) and 45 controls. Patients with BAD also received standard imaging (Se75HCAT) for confirmation. Urine samples were collected and the headspace analysed using an AlphaMOS Fox 4000 electronic nose in combination with an Owlstone Lonestar Field Asymmetric Ion Mobility Spectrometer (FAIMS). A subset was also tested by gas chromatography, mass spectrometry (GCMS). Linear Discriminant Analysis (LDA) was used to explore both the electronic nose and FAIMS data. LDA showed statistical differences between the groups, with reclassification success rates (using an n-1 approach) at typically 83%. GCMS experiments confirmed these results and showed that patients with BAD had two chemical compounds, 2-propanol and acetamide, that were either not present or were in much reduced quantities in the ulcerative colitis and control samples. We believe that this work may lead to a new tool to diagnose BAD, which is cheaper, quicker and easier that current methods.
Phase II Study of Paclitaxel and Carboplatin for Malignant Melanoma (2002)

Conventional chemotherapy in the treatment of malignant melanoma has been disappointingly ineffective. Although the most active single agent is dacarbazine, numerous trials support the activity of platinum analogs against melanoma. Several recent trials also demonstrate the single-agent activity of paclitaxel, and support the administration of these agents together in the treatment of a number of solid tumors. We conducted a phase II study treating patients with metastatic melanoma with paclitaxel as a 3-hour infusion of 175 mg/m2, and carboplatin dosed to yield an area under the curve of 7.5 administered during 30 minutes. Patients were previously untreated or treated once with a regimen not including a platinum or taxane agent and had a performance status of 0 or 1. Seventeen patients (8 males; 9 females; average age 51) were enrolled. Thirty-three percent of patients had disease involving the skin, 40% lungs, 33% lymph nodes, 26% liver, and 13% other visceral organs. Anaphylactic reactions developed in two patients associated with paclitaxel infusion, and the patients were subsequently taken off the study. Of the 15 remaining patients, 3 (20%) had partial responses, 7 (47%) had stable disease, and 5 (33%) showed evidence of progressive disease. Eleven patients experienced grade III or IV hematologic toxicity. All treatment-related toxicities were reversible. There were no treatment-related deaths. The combination of paclitaxel and carboplatin has moderate activity against malignant melanoma, with expected reversible hematologic toxicities. Although not prospectively compared with single agents, the combination of paclitaxel and carboplatin may be a treatment option for some patients. Comparisons with other treatment regimens and the search for additional active compounds against melanoma are needed.
Tyrosine phosphorylation of phospholipase C-γ 2 upon cross-linking of membrane Ig on murine B lymphocytes (1992)

When membrane Ig (mIg) on the surface of B lymphocytes is cross-linked using anti-Ig antibodies, the enzyme phospholipase C (PLC) is activated to cleave inositol phospholipids. Tyrosine kinase inhibitors have been reported to inhibit this event. Therefore, we investigated the effect of cross-linking of mIg on the state of tyrosine phosphorylation of PLC activity in two murine B cell lines and in normal resting mouse B cells. Proteins from lysates of stimulated or unstimulated cells were immunoprecipitated with an antiphosphotyrosine antibody and subsequently assayed for PLC activity. Treatment of the B cell line WEHI-231 with anti-IgM led within 15 to 30 s to a 10- to 20-fold increase in tyrosine-phosphorylated PLC activity. Inositol trisphosphate generation by WEHI-231 cells stimulated under the same conditions demonstrated similar kinetics. Normal resting B cells treated with anti-IgM or anti-IgD demonstrated 2.5- and 4-fold increases, respectively, of tyrosine-phosphorylated PLC activity. To identify the isozyme of PLC that was phosphorylated, we immunoprecipitated PLC-gamma 1 or PLC-gamma 2 with specific antibodies and assessed the amount of tyrosine phosphorylation of these proteins by antiphosphotyrosine immunoblotting. Treatment of WEHI-231 or Bal17 cells with anti-IgM induced an increase in PLC-gamma 2 tyrosine phosphorylation over background levels. There was no detectable tyrosine phosphorylation of PLC-gamma 1 in treated or untreated WEHI-231 cells, whereas anti-IgM-treated Bal17 cells did exhibit low but detectable levels of tyrosine phosphorylation of PLC-gamma 1. In normal resting mouse B cells, there was no detectable PLC-gamma 1, but PLC-gamma 2 was abundant. These observations suggest that PLC-gamma 2 is a significant substrate for the mIg-activated protein tyrosine kinase and may be responsible for mediating mIg stimulation of inositol phospholipid hydrolysis in murine B cells.
A Short Core Region of E-cadherin is Essential for Catenin Binding and is Highly Phosphorylated (1994)

Classical cadherins associate with three cytoplasmic proteins, termed alpha, -beta- and gamma-catenin. This association mediates the attachment of cadherins to the microfilament network, which is believed to be of major importance for cadherin function. Deletion of the carboxyterminal 72-amino acid residues of E-cadherin had been previously shown to prevent catenin binding. Here we have analyzed additional mutants of E-cadherin with deletions within this region and identified a core region of 30 amino acids (E-cadherin pos. 832-862) essential for the interaction with catenins. Phosphorylation analysis of wild-type and mutant E-cadherin indicates that the catenin-binding domain is highly phosphorylated. In particular, the 30 amino acid region contains 8 serine residues which are well conserved among cadherins. To elucidate whether phosphorylation might be important for cadherin-catenin complex formation, site-directed mutagenesis experiments were performed. Partial substitutions of up to 5 of the 8 serine residues in the cluster had no influence on E-cadherin-catenin complex formation and E-cadherin mediated cell adhesion, although phosphorylation of E-cadherin was reduced. In contrast, substitution of the whole serine cluster completely abolished phosphorylation and affected complex formation with catenins. These results suggest that E-cadherin-catenin interaction may be regulated by phosphorylation of the catenin-binding domain, which might represent one molecular mechanism to regulate cadherin mediated cell adhesion.
Neutrophil and monocyte activation in chronic kidney disease patients under hemodialysis and its relationship with resistance to recombinant human erythropoietin and to the hemodialysis procedure (2010)

The aim of the present work was to further clarify leukocyte activation due to hemodialysis (HD) procedures and to investigate its relationship with recombinant human erythropoietin resistance. Therefore, we studied the expression of CXCR1 and CD11b on neutrophils, as well as the monocyte expression of CD11b, HLA-DR, and CD14. We studied 34 chronic kidney disease (CKD) patients under HD and recombinant human erythropoietin treatment (26 responders and 8 nonresponders to recombinant human erythropoietin therapy). All CKD patients' blood samples were collected before and immediately after the HD procedure. Eighteen healthy individuals (blood donors) were also studied as a control group. Hematological data, neutrophil (CD11b and CXCR1), and monocyte (CD11b, HLA-DR, and CD14) cell surface markers were measured in all patients (before and after the HD procedure) and controls. When compared with the controls, CKD patients presented a significant decrease in CXCR1 neutrophil expression, and in CD14 monocyte expression, accompanied by a significant increase in HLA-DR monocyte expression. When comparing the 2 groups of patients, we found that nonresponders showed an additional decrease in CXCR1 neutrophil expression. After the HD procedure, a statistically significant increase in CD14 and CD11b monocyte surface markers and a decrease in CXCR1 neutrophil expression and in HLA-DR monocyte expression was found. These data further strengthen our previous studies, showing that neutrophils and monocytes are activated in CKD patients, particularly in nonresponder patients. Moreover, this activation is due, at least in part, to the HD procedure, although we should not exclude that it can also be due to the enhanced inflammatory process observed in nonresponder patients.
Safety and Efficacy of Low-dose Pioglitazone (7.5 mg/day) vs. Standard-dose Pioglitazone (15 mg/day) in Japanese Women with Type 2 Diabetes Mellitus (2006)

It is well known that pioglitazone, a potent thiazolidinedione, improves metabolic control. However, weight gain or peripheral edema may be of major clinical concern when using this agent. The purpose of our study was to prospectively evaluate the effects of low-dose pioglitazone (7.5 mg/day) on metabolic control, weight gain and the incidence of edema compared with a standard dose of pioglitazone (15.0 mg/day) in patients with type 2 diabetes mellitus (T2DM). Ninety-five Japanese female patients (mean age 58.4 +/- 10.4 years) with newly diagnosed T2DM were selected for this study. They were randomly divided into the following 2 groups according to therapy regimens, and examined every month for 6 months after diagnosis. Group A consisted of 54 patients treated with low-dose pioglitazone orally; Group B, the control-group, consisted of 41 patients treated with standard-dose pioglitazone orally. The incidence of peripheral edema was significantly much lower in group A (2/54) than in group B (11/41) (p = 0.0014). In addition, % change of body weight during the 6-month treatment in group A was significantly less than that in group B (p < 0.0001). On the other hand, the % change of biochemical parameters including HbA1c did not differ significantly between group A and group B, although glucose and lipid control significantly improved from baseline in both groups. Our results demonstrate the safety and efficacy of low-dose pioglitazone, suggesting that it could be another good choice of treatment for Japanese women with T2DM.
An Ontology for Mobile Video Games (2010)

Current ontology research and practice had its origins in declarative AI knowledge representations such as semantic networks and frames, which were primarily designed for runtime reasoning and inference. This paper examines the potential for the use of object-oriented standards in ontology modelling. We have investigated the use of UML and OCL for the representation of information system ontologies and have constructed an example of an ontology in the domain of mobile video games. UML is now being used for designing artifacts that are more declarative, since researchers are developing formal semantics for UML. These efforts will remove one of the most commonly stated criticisms of the suitability of UMLfor representing formal models such as ontologies.
Novel Phosphoramidate Prodrugs of N-Acetyl-(d)-Glucosamine with Antidegenerative Activity on Bovine and Human Cartilage Explants (2012)

(D)-Glucosamine and other nutritional supplements have emerged as safe alternative therapies for osteoarthritis (OA), a chronic and degenerative articular joint disease. In our preceding paper, a series of novel O-6 phosphate N-acetyl (d)-glucosamine prodrugs aimed at improving the oral bioavailability of N-acetyl-(d)-glucosamine as its putative bioactive phosphate form were shown to have greater chondroprotective activity in vitro when compared to the parent agent. In order to extend the SAR studies, this work focuses on the O-3 and O-4 phosphate prodrugs of N-acetyl-(d)-glucosamine bearing a 4-methoxy phenyl group and different amino acid esters on the phosphate moiety. Among the compounds, the (l)-proline amino acid-containing prodrugs proved to be the most active of the series, more effective than the prior O-6 compounds, and well processed in chondrocytes in vitro. Data on human cartilage support the notion that these novel O-3 and O-4 regioisomers may represent novel promising leads for drug discovery for osteoarthritis.
Content-Based Digital Image Retrieval based on Multi-Feature Amalgamation (2013)

In actual implementation, digital image retrieval are facing all kinds of problems. There still exists some difficulty in measures and methods for application. Currently there is not a unambiguous algorithm which can directly shown the obvious feature of image content and satisfy the color, scale invariance and rotation invariance of feature simultaneously. So the related technology about image retrieval based on content is analyzed by us. The research focused on global features such as seven HU invariant moments, edge direction histogram and eccentricity. The method for blocked image is also discussed. During the process of image matching, the extracted image features are looked as the points in vector space. The similarity of two images is measured through the closeness between two points and the similarity is calculated by Euclidean distance and the intersection distance of histogram. Then a novel method based on multi-features amalgamation is proposed, to solve the problems in retrieval method for global feature and local feature. It extracts the eccentricity, seven HU invariant moments and edge direction histogram to calculate the similarity distance of each feature of the images, then they are normalized. Contraposing the interior of global feature the weighted feature distance is adopted to form similarity measurement function for retrieval. The features of blocked images are extracted with the partitioning method based on polar coordinate. Finally by the idea of hierarchical retrieval between global feature and local feature, the results are output through global features like invariant moments etc. These results will be taken as the input of local feature match for the second-layer retrieval, which can improve the accuracy of retrieval effectively.
Imaging Guided Percutaneous Irreversible Electroporation: Ultrasound and Immunohistological Correlation (2007)

Preliminary results of percutaneous irreversible electroporation (PIE) on swine liver as a novel non-thermal ablation are presented. The goal of this study was to evaluate the feasibility of using irreversible electroporation in more clinically applicable manner, a percutaneous method, and to investigate a possible role of apoptosis in PIE-induced cell death. We performed PIE on four swine livers under real-time ultrasound guidance. The lesions created by PIE were imaged with ultrasound and were correlated with histology data, including pro-apoptotic marker. A total of 11 lesions were created with a mean size of 16.8 cm(3) in 8.4 +/- 1.8 minutes. Real-time monitoring was performed and a correlation of (+) 2 +/- 3.2 mm in measurement comparison between ultrasound and gross pathologic measurements was demonstrated. Complete hepatic cell death without structural destruction, unaffected by heat-sink effect, and with a sharp demarcation between the ablated zone and the non-ablated zone were observed. Immunohistological analysis confirmed complete apoptotic cell death by PIE on Von Kossa, BAX, and H&E staining. In summary, PIE can provide a novel and unique ablative method with real-time monitoring capability, ultra-short procedure time, non-thermal ablation, and well-controlled and focused apoptotic cell death.
BNAs: novel nucleic acid analogs with a bridged sugar moiety (2002)

This article deals with our recent studies on the synthesis of BNAs (Bridged Nucleic Acids), novel nucleic acid analogs bearing a preorganized sugar conformation by a bridged structure. Duplex- and triplex-forming abilities of the BNA modified oligonucleotides are also described.
Laterally driven polysilicon resonant microstructures (2003)

Interdigitated finger (comb) structures are demonstrated to be effective for electrostatically exciting the resonance of polysilicon microstructures parallel to the plane of the substrate. Linear plates suspended by a folded-cantilever truss and torsional plates suspended by spiral and serpentine springs are fabricated from a 2- mu m-thick phosphorus-doped low-pressure chemical vapor deposited polysilicon film. Resonance is observed visually, with frequencies ranging from 18 kHz to 80 kHz and quality factors from 20 to 130. Simple beam theory is adequate for calculating the resonant frequencies, using a Young's modulus of 140 GPa and neglecting residual strain in the released structures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>