gebhart/patrepeval huggingface dataset:
Harnessing Gene Conversion in Chicken B Cells to Create a Human Antibody Sequence Repertoire (2013)

Transgenic chickens expressing human sequence antibodies would be a powerful tool to access human targets and epitopes that have been intractable in mammalian hosts because of tolerance to conserved proteins. To foster the development of the chicken platform, it is beneficial to validate transgene constructs using a rapid, cell culture-based method prior to generating fully transgenic birds. We describe a method for the expression of human immunoglobulin variable regions in the chicken DT40 B cell line and the further diversification of these genes by gene conversion. Chicken VL and VH loci were knocked out in DT40 cells and replaced with human VK and VH genes. To achieve gene conversion of human genes in chicken B cells, synthetic human pseudogene arrays were inserted upstream of the functional human VK and VH regions. Proper expression of chimeric IgM comprised of human variable regions and chicken constant regions is shown. Most importantly, sequencing of DT40 genetic variants confirmed that the human pseudogene arrays contributed to the generation of diversity through gene conversion at both the Igl and Igh loci. These data show that engineered pseudogene arrays produce a diverse pool of human antibody sequences in chicken B cells, and suggest that these constructs will express a functional repertoire of chimeric antibodies in transgenic chickens.
Analysis of reconstruction of radiated acoustic pressure fields by using the HELS method (2000)

This paper presents a detailed analysis of reconstruction of the acoustic pressure fields radiated from a partially vibrating sphere by using the Helmholtz equation-least squares (HELS) method [Z. Wang and S. F. Wu, J. Acoust. Soc. Am. 102, 2020–2032 (1997); 104, 2054–2060 (1998)]. The objectives of this study are to gain insight into an acoustic inverse problem and to develop guidelines that may be helpful in the future reconstruction work. Because of the complexities involved, many questions such as where and how many measurements should be taken, how many expansion terms are necessary for a given number of measurements, etc., remain unanswered. These questions will be tackled here. The reasons for selecting a partially vibrating sphere are twofold: (1) the resulting acoustic pressure field contains a very pronounced near-field effect; and (2) analytic results are known so the reconstructed acoustic pressures can be checked rigorously. The impact of a loss of the near-field effect on reconstruction will be investigated. The effects of measurement distance, area, and shape on the accuracy of reconstruction will be examined. The efficiency of reconstruction using the HELS method as the increase in frequency will also be studied. [Work supported by the NSF, Grant No. CMS-9802847.]
1<i>α</i>,24(<i>S</i>)-dihydroxyvitamin D2: a biologically active product of 1<i>α</i>-hydroxyvitamin D2 made in the human hepatoma, Hep3B (1995)

A major metabolite of the vitamin D analogue 1 alpha-hydroxyvitamin D2 in human liver cells in culture has been identified as 1 alpha,24(S)-dihydroxyvitamin D2 [1 alpha,24(S)-(OH)2D2]. 1 alpha-Hydroxyvitamin D3 incubated with the same cells gives rise to predominantly 25- and 27-hydroxylated products. Our identification of 1 alpha,24(S)-dihydroxyvitamin D2 is based on comparisons of the liver cell metabolite with chemically synthesized 1 alpha,24(S)-(OH)2D2 and 1 alpha,24(R)-(OH)2D2 by using HPLC, GC and GC-MS techniques. The stereochemical orientation of the 24-hydroxyl group was inferred after X-ray-crystallographic analysis of the 24(R)-OH epimer. 1 alpha,24(S)-Dihydroxyvitamin D2 binds strongly to the vitamin D receptor and is biologically active in growth hormone and chloramphenicol acetyltransferase reporter gene expression systems in vitro, but binds poorly to rat vitamin D-binding globulin, DBP. We suggest that this metabolite, 1 alpha,24(S)-(OH)2D2, possesses the spectrum of biological properties to be useful as a drug in the treatment of psoriasis, metabolic bone disease and cancer.
Purification and properties of deacetoxycephalosporin C synthase from recombinant Escherichia coli and its comparison with the native enzyme purified from Streptomyces clavuligerus (1989)

A putatively rate-limiting synthase (expandase) of Streptomyces clavuligerus was stabilized in vitro and purified 46-fold from cell-free extracts; a major enriched protein with a Mr of 35,000 was further purified by electrophoretic elution. Based on a 22-residue amino-terminal sequence of the protein, the synthase gene of S. clavuligerus was cloned and expressed in Escherichia coli (Kovacevic, S., Weigel, B.J., Tobin, M.B., Ingolia, T.D., and Miller, J. R. (1989) J. Bacteriol. 171, 754-760). The synthase protein was detected mainly from granules of recombinant E. coli. The recombinant synthase was solubilized from the granules by urea, and for the first time a highly active synthase was purified to near homogeneity. The synthase was a monomer with a Mr of 34,600 and exhibited two isoelectric points of 6.1 and 5.3. Its catalytic activity required alpha-ketoglutarate, Fe2+, and O2, was stimulated by dithiothreitol or ascorbate but not by ATP, and was optimal at pH 7.0 in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer and at 36 degrees C. The Fe2+ requirement was specific, and at least one sulfhydryl group in the purified enzyme was apparently essential for the ring expansion. The Km values of the enzyme for penicillin N and alpha-ketoglutarate were 29 and 18 microM, respectively, and the Ka for Fe2+ was 8 microM. The recombinant synthase was indistinguishable from the native synthase of S. clavuligerus by those biochemical properties. In addition to the enzymic ring expansion of penicillin N to deacetoxycephalosporin C, the recombinant synthase catalyzed a novel hydroxylation of 3-exomethylenecephalosporin C to deacetylcephalosporin C.
Adjustable Speed Drive Bearing Fault Detection via Wavelet Packet Decomposition (2006)

Adjustable speed drives perform many vital control functions in the industry serving in such diverse applications as rolling mills and variable speed compressors, fans and pumps. When an adjustable speed drive fails due to a bearing failure, it is usually catastrophic. Bearing defects introduce vibration anomalies that alter the current characteristic frequencies. This paper addresses the application of motor current signature analysis using wavelet packet decomposition to detect bearing fault in adjustable speed drives
CuO/TiO2 Nanocomposites: Effect of Calcination on Photocatalytic Hydrogen Production (2019)

Hydrothermally synthesized TiO 2 nanorods were subjected to calcination from 350 to 550 °C and tested their catalytic performance for hydrogen (H 2 ) production in aqueous glycerol solution under solar irradiation. High rate of H 2 evolution ca.300 µmol.h −1 .g −1 cat was recorded with TiO 2 nanorods calcined at 500 °C. The nanocomposites were prepared by varying Cu-loading 0.1 to 2.0 wt% and activated at 350 or 500 °C. About 25 folds enhancement in H 2 production rate was observed with 1.5% CuO/TiO 2 nanorods than calcined ones. Catalyst characterization revealed that as-synthesized TiO 2 material was nanorods with trititanate crystal structure. The optimized photocatalyst confirmed presence of copper in + 2 state and mixed crystal structure of TiO 2 (B) and anatase. Based on the experimental results high photocatalytic activity observed is due to improved crystallanity of TiO 2 nanorods and CuO as well
Medicinal Chemistry and Properties of 1,2,4-Thiadiazoles (2005)

1,2,4-Thiadiazole is a distinctive class of small heterocyclic thiol trapping agents that serve as an interesting pharmacophore in the design of inhibitors targeting the cysteine residues of proteins. X-Ray crystal structures of enzyme-inhibitor complex indicate that the cysteine thiol reacts with the N-S bond of the thiadiazole moiety to form a disulfide bond resulting in the inactivation of the enzymes. This review addresses the medicinal chemistry and various properties of 1,2,4-thiadiazoles in their potential as new electrophilic "warheads" for targeting the cysteine residues of biomolecules (e.g, H+/K+ ATPase), and cysteine-dependent enzymes (e.g., cathepsin B and transglutaminase).
First results of digital topography applied to macromolecular crystals (2004)

An inexpensive digital CCD camera was used to record X-ray topographs directly from large imperfect crystals of cubic insulin. The topographs recorded were not as detailed as those which can be measured with film or emulsion plates, but do show great promise. Six reflections were recorded using a set of finely spaced stills encompassing the rocking curve of each reflection. A complete topographic reflection profile could be digitally imaged in minutes. Interesting and complex internal structure was observed by this technique. The CCD chip used in the camera has anti-blooming circuitry and produced good data quality, even when pixels became overloaded.
A dual-mode wireless power transfer system using multi-frequency programmed pulse width modulation (2016)

Multi-frequency wireless power transfer (WPT) is advantageous in facilitating compatibility with different WPT standards. However, implementing a multi-frequency transmitter often requires compromises in system size, complexity, power transfer capability, or output regulation. In this paper, a single-inverter based dual-mode WPT system is proposed. The system employs a multi-frequency programmed pulse width modulation (MFPWM) scheme. This dual-frequency modulated inverter can simultaneously generate and regulate 100 kHz and 6.78 MHz outputs, which facilitates the development of multi-standard WPT technology for consumer electronics. In addition, the principle of the proposed modulation is illustrated, where two different frequencies are concurrently modulated in the programmed pulse train of square waveforms, while eliminating certain harmonics in between. Design tradeoffs and constraints are examined through analytical circuit models. Finally, experimental results are provided to verify the effectiveness of the proposed WPT system.
[F3–07–02]: TAU IMMUNOTHERAPY PREVENTS THE SPREAD AND PROMOTES THE CLEARANCE OF PATHOLOGY IN MICE (2017)

In Alzheimer's disease (AD) all six isoforms of tau are abnormally hyperphosphorylated. Tau pathology in the absence of Abeta pathology is a hallmark of a family of neurodegenerative disorders, called tauopathies. Without exception tau pathology is made up of hyperphosphorylated protein. Given the involvement of six isoforms there are multiple possible patterns of tau hyperphosphorylation. Unlike normal tau which binds to microtubule protein subunit tubulin and promotes its assembly and stabilizes the microtubule network, the ptau instead binds to normal tau and templates it in a prion-like fashion into tau oligomers and filaments. We took advantage of this finding and carried out immunization with tau antibodies 43D against tau6–18 and 77E9 against tau184–195, targeting the amino-terminal domains of tau in 3xTg-AD mouse model of AD and frontotemporal dementia. We found that with this strategy we can rescue not only tau but also Abeta pathology and cognitive impairment in 3xTg-AD mice. Furthermore, we found that the immunotherapy can also prevent the spread of AD-ptau induced pathology in tau transgenic mice. Immunization targeting the amino-terminal domain of tau has the potential to lead to an effective disease modifying treatment for AD and related tauopathies.
Morphology and Entrapped Enzyme Performance in Inkjet-Printed Sol–Gel Coatings on Paper (2014)

We recently reported on the multilayer printing of sol–gel/enzyme bioinks onto porous filter paper to create bioactive paper test strips. The method involves printing of four inks: a polymer underlayer, a sol–gel-based silica layer, an acetylcholinesterase (AChE) enzyme layer, and finally a top layer of silica. To improve our understanding of the nature of these printed materials, filter paper printed with various ink components was characterized by activity assays (with and without protease treatment), confocal microscopy to assess the location and mixing of layers, and scanning electron microscopy of deposited inks to assess the morphology and ink location. Although the silica and enzyme solutions were printed sequentially, they formed a composite material within the porous paper network and coated only the fibers as a 35 ± 15 nm thin film without filling the macropores. The silica coating on the cellulose fibers was sufficiently flexible to allow bending of the paper substrate, unlike traditional silica thin films. The protease assay results showed that the AChE was more protected as the amount of sol–gel-derived silica printed on paper was increased. The top layer of sol–gel ink was found to play a critical role in protection against proteolysis, while the bottom layer of sol–gel ink was found to be necessary to prevent the potential inhibition of AChE by the cationic polymer (used as a capture agent for the product of the enzymatic reaction). Overall, the data show that inkjet-printed sol–gel materials form thin, protein-entrapping films that are suitable for the production of printed biosensors.
MSI‐Testing in Hereditary Non‐Polyposis Colorectal Carcinoma (HNPCC) (2004)

Genomic instability at simple repeated sequences, termed microsatellite instability (MSI), plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC) more than 90% of cases show MSI, whereas only 10-15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI) proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols for MSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.
Simultaneous Atrial and Ventricular Anti‐Tachycardia Pacing as a Novel Method of Rhythm Discrimination (2006)

Background: Inappropriate shocks remain a problem in patients with defibrillators (ICD). Objective: To evaluate a new discrimination algorithm for supraventricular (SVT) and ventricular (VT) tachycardias, based on the response to simultaneous (A+V) atrial (A) and ventricular (V) anti‐tachycardia pacing (ATP). Methods: Patients undergoing electrophysiological testing or dual‐chamber implantable cardioverter‐defibrillator (ICD) implantation were enrolled (N = 32) and underwent A+V ATP through a Marquis ICD with investigational software. If persisting after ATP, the rhythm was classified as VT if the first electrical event was sensed on the V channel and as an SVT otherwise. Results: Arrhythmia sequences (N = 275; 53 VT; 222 SVT) were analyzed in 26 patients (age = 51 ± 17 years, 13 men, LVEF = 0.49 ± 0.14). In response to A+V ATP, 55% of SVT versus 41% of VT episodes were terminated (P = NS). Termination of VT but not of SVT was more likely with faster (50% at ATP/arrhythmia cycle length (CL) = 0.81 vs 8% at ATP/arrhythmia CL = 0.88, P = 0.02) but not with longer ATP bursts (P = NS). Of the 115 arrhythmias that persisted after A+V ATP, the algorithm correctly classified 24 of 24 VT (GEE‐adjusted sensitivity = 100%) and 85 of 91 SVT (GEE‐adjusted specificity = 93%). Proarrhythmia was noted after two A+V ATP, in the form of atrial fibrillation induction and VT acceleration. Conclusions: We describe a new algorithm that can discriminate between SVT and VT with a high sensitivity and specificity. This form of ATP can terminate 55% of SVT sequences. The performance of this new algorithm merits further testing in a large population of dual‐chamber ICD patients.
Indium-doped molybdenum oxide as a new p-type transparent conductive oxide (2011)

New p-type transparent conductive oxide materials, MoO3:In single crystal nanowires and amorphous films, are synthesized in this work. Both nanowires and amorphous films exhibit high optical transmittance, 80–88% for 80 nm thick films at 400–800 nm wavelength, and low resistivity (down to 5.98 × 10−4 Ω cm) suitable for photovoltaic device applications. The amorphous films are also deposited on flexible polyimide substrates and exhibit excellent electrical properties even after bending. Besides, p-MoO3:In/i-ZnO/n-AZO devices are fabricated to demonstrate the potential for all-transparent flexible electronic applications.
Method for Detection of Respiratory Cycle-Related EEG Changes in Sleep-Disordered Breathing (2004)

In this child with SDB, the EEG varied with respiratory cycles to a quantifiable extent that changed after adenotonsillectomy. We speculate that RCREC may reflect brief but extremely numerous microarousals.
New perspective in process optimisation of variable pitch milling (2009)

Stability analysis of variable-pitch milling process offers a mathematically challenging task due to the complex nature of the ensuing regenerative chatter dynamics. It can be reduced to a problem of stability assessment of a Linear Time-Invariant (LTI) Systems with multiple independent delays. This problem can be solved by a recent paradigm; the Cluster Treatment of Characteristic Roots (CTCR). This paper suggests an optimisation procedure based on the CTCR. The objective function entails two compromising components: to maximise the metal removal rate while creating the best chatter rejection ability. The end result determines both the cutter geometry and the operating conditions.
Identification of key genes involved in polysaccharide bioflocculant synthesis in <i>Bacillus licheniformis</i> (2016)

The present study reports the sequenced genome of Bacillus licheniformis CGMCC 2876, which is composed of a 4,284,461 bp chromosome that contains 4,188 protein-coding genes, 72 tRNA genes, and 21 rRNA genes. Additional analysis revealed an eps gene cluster with 16 open reading frames. Conserved Domains Database analysis combined with qPCR experiments indicated that all genes in this cluster were involved in polysaccharide bioflocculant synthesis. Phosphoglucomutase and UDP-glucose pyrophosphorylase were supposed to be key enzymes in polysaccharide secretion in B. licheniformis. A biosynthesis pathway for the production of polysaccharide bioflocculant involving the integration of individual genes was proposed based on functional analysis. Overexpression of epsDEF from the eps gene cluster in B. licheniformis CGMCC 2876 increased the flocculating activity of the recombinant strain by 90% compared to the original strain. Similarly, the crude yield of polysaccharide bioflocculant was enhanced by 27.8%. Overexpression of the UDP-glucose pyrophosphorylase gene not only increased the flocculating activity by 71% but also increased bioflocculant yield by 13.3%. Independent of UDP-N-acetyl-D-mannosamine dehydrogenase gene, flocculating activity, and polysaccharide yield were negatively impacted by overexpression of the UDP-N-acetylglucosamine 2-epimerase gene. Overall, epsDEF and gtaB2 were identified as key genes for polysaccharide bioflocculant synthesis in B. licheniformis. These results will be useful for further engineering of B. licheniformis for industrial bioflocculant production. Biotechnol. Bioeng. 2017;114: 645-655. © 2016 Wiley Periodicals, Inc.
Abstract 15945: A Novel Defibrillation Tool: Percutaneously Delivered, Partially-insulated Epicardial Defibrillation (2016)

Introduction: Epicardial defibrillator systems typically require surgical access for implantation. Hypothesis: To develop an entirely percutaneous defibrillator system with partially insulated epic...
Pituitary adenylate cyclase-activating polypeptide prevents contrast-induced nephropathy in a novel mouse model (2013)

We determined whether pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) prevents contrast-induced nephropathy using human renal proximal tubule epithelial (HK-2) cells and homozygous endothelial nitric oxide synthase-deficient (eNOS(-/-)) mice as a novel in vivo model. Cultured HK-2 cells were pretreated with 10(-9)-10(-6) mol/L PACAP or vasoactive intestinal peptide (VIP) for 1 h, and then exposed to ionic (Urografin) or nonionic (iohexol) contrast media at 50 mg iodine/mL for 24 h. Male eNOS(-/-) mice received Urografin (1.85 g iodine/kg) intravenously after water deprivation for 24 h, and PACAP38 (10 μg) intraperitoneally 1 h before and 12 h after Urografin injection. Urografin and iohexol increased lactate dehydrogenase and kidney injury molecule 1 in the culture medium, induced apoptosis, and inhibited cell proliferation in HK-2 cell cultures. PACAP38 and VIP reduced these changes in a dose-dependent manner. PACAP38 was more potent than VIP. In eNOS(-/-) mice, Urografin raised serum creatinine and cystatin C levels, caused renal tubule damage, induced apoptosis, and promoted neutrophil influx. Urografin also increased kidney protein levels of proinflammatory cytokines, and kidney mRNA levels of proinflammatory cytokines, kidney injury biomarkers, and enzymes responsible for reactive oxygen and nitrogen species. PACAP38 significantly reduced these Urografin-induced changes in eNOS(-/-) mice. This study shows that both Urografin and iohexol are toxic to HK-2 cells, but Urografin is more toxic than iohexol. Urografin causes acute kidney injury in eNOS(-/-) mice. PACAP38 protects HK-2 cells and mouse kidneys from contrast media and is a potential therapeutic agent for contrast-induced nephropathy.
Pharmacokinetics and In Vivo Efficacy of Pyrazolopyrimidine, Pyrrolopyrimidine, and 5-Aminopyrazole-4-Carboxamide Bumped Kinase Inhibitors against Toxoplasmosis (2018)

Bumped kinase inhibitors (BKIs) have been shown to be potent inhibitors of Toxoplasma gondii calcium-dependent protein kinase 1. Pyrazolopyrimidine and 5-aminopyrazole-4-carboxamide scaffold-based BKIs are effective in acute and chronic experimental models of toxoplasmosis. Through further exploration of these 2 scaffolds and a new pyrrolopyrimidine scaffold, additional compounds have been identified that are extremely effective against acute experimental toxoplasmosis. The in vivo efficacy of these BKIs demonstrates that the cyclopropyloxynaphthyl, cyclopropyloxyquinoline, and 2-ethoxyquinolin-6-yl substituents are associated with efficacy across scaffolds. In addition, a broad range of plasma concentrations after oral dosing resulted from small structural changes to the BKIs. These select BKIs include anti-Toxoplasma compounds that are effective against acute experimental toxoplasmosis and are not toxic in human cell assays, nor to mice when administered for therapy. The BKIs described here are promising late leads for improving anti-Toxoplasma therapy.