gebhart/patrepeval huggingface dataset:
In Vitro Transcription and Translation Protocols (1995)

Most laboratories conducting studies that use molecular biology techniques employ in vitro transcription and translation systems as a routine part of their day-to-day research. The commercial availability of purified bacterial RNA polymerase and the availability of robust tra- lation systems has made in vitro systems attractive not only as an alt- native to the in vivo expression of genes, but also as good model systems for studying specific aspects of transcription and translation. Although fairly efficient eukaryotic translation systems have been established for a number of years, reconstitution of transcription in vitro has proved to be more difficult. Recent improvements in fractionation techniques and the cloning of proteins involved in transcription have made this a fast moving area of research. Considerable progress has also been made in recent years in developing in vitro systems to study transcription and translation in chloroplasts and mitochondria, together with systems for the study of protein import. In Vitro Transcription and Translation Protocols provides many detailed experimental procedures for prokaryotic transcription and translation systems, together with protocols for many key techniques used in the analysis of eukaryotic transcription. In keeping with the successful format of preceding volumes of the Methods in Molecular Biology series, step-by-step instructions are provided, together with extensive notes that cover troubleshooting and special tips considered important
Conjugation Site Heterogeneity Causes Variable Electrostatic Properties in Fc Conjugates (2013)

Immunoconjugates, including antibody-drug conjugates and Fc-conjugates, represent a rapidly growing class of therapeutics undergoing clinical development. Despite their growing popularity, the high intrinsic heterogeneity of immunoconjugates often complicates the development process and limits their widespread application. In particular, immunoconjugate charge variants exhibit markedly different colloidal stabilities, solubilities, pharmacokinetics, and tissue distributions. Charge variants arise spontaneously due to degradation and, depending on the type of drug, linker, and conjugation site, through drug conjugation. Electrostatic changes in naked antibodies often result in poor performance characteristics, and therefore, charge alterations due to degradation are critical to control. Charge properties are expected to be equally important to producing well-behaved ADCs. Charge-based methods of analysis, such as isoelectric focusing and ion exchange chromatography, are capable of probing the underlying complexities within immunoconjugate drug products. Despite the utility of these methods, there are only a few published reports of charge-based assays applied to immunoconjugates. In the present study, we sought to identify the effects of chemical conjugation on the electrostatic properties of Fc-conjugates. In order to minimize the effects of post-translational modifications (e.g., deamidation), a single Fc charge variant was isolated prior to conjugation of a fluorescent probe, Alexa Fluor 350, to the side chains of lysine residues. The resulting Fc-conjugates were assessed by a variety of analytical techniques, including isoelectric focusing and ion exchange chromatography, to determine their charge properties.
Zone Plates and Their Aberrations (1972)

The zone plate is an optical device that depends on interference, not reflection or refraction, for its image-forming properties. Although the irradiance at the focus is only 110 that of a lens with the same aperture, a zone plate with 100 or more zones is capable of resolution equal to that of the lens. Zone plates can be used in spectral regions where conventional optics are unavailable and for special applications in the visible spectrum. This paper derives the third-order and chromatic aberrations of the zone plate. The image may be diffraction limited only if the illumination is relatively monochromatic. Like the pinhole camera, the zone plate turns out not to suffer from linear distortion, even at very wide fields.
UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras (2018)

UbiA prenyltransferase domain-containing protein 1 (UBIAD1) plays a key role in biosynthesis of vitamin K<sub>2</sub> and coenzyme Q10 using geranylgeranyl diphosphate (GGPP). However, the mechanism by which UBIAD1 participates in tumorigenesis remains unknown. This study show that UBIAD1 interacts with H-Ras, retains H-Ras in the Golgi apparatus, prevents H-Ras trafficking from the Golgi apparatus to the plasma membrane, blocks the aberrant activation of Ras/MAPK signaling, and inhibits the proliferation of bladder cancer cells. In addition, GGPP was required to maintain the function of UBIAD1 in regulating the Ras/ERK signaling pathway. A Drosophila model was employed to confirm the function of UBIAD1/HEIX in vivo. The activation of Ras/ERK signaling at the plasma membrane induced melanotic masses in Drosophila larvae. Our study suggests that UBIAD1 serves as a tumor suppressor in cancer and tentatively reveals the underlying mechanism of melanotic mass formation in Drosophila.
Clinicopathological Significance of Major Histocompatibility Complex Class I-Related Chain A and B Expression in Thyroid Cancer (2006)

MICA/B expression is up-regulated in thyroid cancer, probably due to the activation of the MAPK pathway. MICA/B in thyroid cancer plays an important role in NK-92 cell-mediated cytotoxicity.
MESA and trading market cycles (1992)

No Change. No Change. No Change. Moving Averages. Momentum Functions. Measuring Market Spectra. MESA Algorithm Discussion. Sinewave Indicator. Instantaneous Trendline. Making Standard Indicators Adaptive. Trading the Cycle Mode. Profitable Stock Market Systems.
Modification of a Tumor-Derived Peptide at an HLA-A2 Anchor Residue Can Alter the Conformation of the MHC-Peptide Complex: Probing with TCR-Like Recombinant Antibodies (2002)

A common assumption about peptide binding to the class I MHC complex is that each residue in the peptide binds independently. Based on this assumption, modifications in class I MHC anchor positions were used to improve the binding properties of low-affinity peptides (termed altered peptide ligands), especially in the case when tumor-associated peptides are used for immunotherapy. Using a new molecular tool in the form of recombinant Abs endowed with Ag-specific MHC-restricted specificity of T cells, we show that changes in the identity of anchor residues may have significant effects, such as altering the conformation of the peptide-MHC complex, and as a consequence, may affect the TCR-contacting residues. We herein demonstrate that the binding of TCR-like recombinant Abs, specific for the melanoma differentiation Ag gp100 T cell epitope G9-209, is entirely dependent on the identity of a single peptide anchor residue at position 2. An example is shown in which TCR-like Abs can recognize the specific complex only when a modified peptide, G9-209-2 M, with improved affinity to HLA-A2 was used, but not with the unmodified natural peptide. Importantly, these results demonstrate, using a novel molecular tool, that modifications at anchor residues can dramatically influence the conformation of the MHC peptide groove and thus may have a profound effect on TCR interactions. Moreover, these results may have important implications in designing modifications in peptides for cancer immunotherapy, because most such peptides studied are of low affinity.
The Impact of Next‐Generation Sequencing Technologies on Metagenomics (2011)

This chapter contains sections titled: Introduction Instrumentation and Reactions Features of NGS Platforms Types of NGS Applications Computational Challenges Conclusions Internet Resources References
Highly Reliable Silicon Nitride Thin Films Made by Jet Vapor Deposition (1995)

This paper reports our results on the properties of gate-quality silicon nitride thin films produced by the jet vapor deposition (JVD) technique at room temperature. It will be shown that the electrical properties and reliability of the metal-nitride-silicon (MNS) capacitors, in terms of their densities of interface traps, leakage current, and resistance against hot-carrier or radiation damage, are significantly better than similar devices made by any other deposited nitrides previously reported.
Diffusion and Short-Term Efficacy of Botulinum Toxin A After the Addition of Hyaluronidase and Its Possible Application for the Treatment of Axillary Hyperhidrosis (2003)

BACKGROUND Botulinum toxin adequately treats hyperkinetic facial lines and hyperhidrosis. Higher doses of botulinum toxin appear to enhance efficacy and longevity possibly through greater evenness of diffusion; however, recurrent treatments with higher doses are expensive. OBJECTIVE To admix botulinum toxin with hyaluronidase and to test whether there is maintenance of efficacy, a spread of effect, and possibly a decrease in required dose compared with botulinum toxin. METHODS Six patients participated in a double-blinded side-to-side comparison pilot study with photographic analysis for frontalis overactivity and Minor's iodine and gravimetric testing for axillary hyperhidrosis. RESULTS Initial efficacy of botulinum with admixed hyaluronic acid appeared maintained with possibly increased diffusion when hyaluronic acid is added. No difference was evident on short-term review of patients treated with 50 U of botulinum in one axilla compared with the contralateral side injected with 25 U with admixed hyaluronidase. CONCLUSION There may be a role for hyaluronic acid in aiding diffusion and decreasing the required dose of botulinum toxin in hyperhidrosis axillaris.
Epitaxial Growth of DNA-Assembled Nanoparticle Superlattices on Patterned Substrates (2013)

DNA-functionalized nanoparticles, including plasmonic nanoparticles, can be assembled into a wide range of crystalline arrays via synthetically programmable DNA hybridization interactions. Here we demonstrate that such assemblies can be grown epitaxially on lithographically patterned templates, eliminating grain boundaries and enabling fine control over orientation and size of assemblies up to thousands of square micrometers. We also demonstrate that this epitaxial growth allows for orientational control, systematic introduction of strain, and designed defects, which extend the range of structures that can be made using superlattice assembly. Ultimately, this will open the door to integrating self-assembled plasmonic nanoparticle materials into on-chip optical or optoelectronic platforms.
Latrunculin A and Its C-17- O -Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells (2008)

The marine-derived macrolides latrunculins A ( 1) and B, from the Red Sea sponge Negombata magnifica, have been found to reversibly bind actin monomers, forming a 1:1 complex with G-actin and disrupting its polymerization. The microfilament protein actin is responsible for several essential functions within the cell such as cytokinesis and cell migration. One of the main binding pharmacophores of 1 to G-actin was identified as the C-17 lactol hydroxyl moiety that binds arginine 210 NH. Latrunculin A-17- O-carbamates 2- 6 were prepared by reaction with the corresponding isocyanates. Latrunculin A ( 1) and carbamates 4- 6 displayed potent anti-invasive activity against the human highly metastatic human prostate cancer PC-3M cells in a Matrigel assay at a concentration range of 50 nM to 1 microM. Latrunculin A ( 1, 500 nM) decreased the disaggregation and cell migration of PC-3M-CT+ spheroids by 3-fold. Carbamates 4 and 5 were 2.5- and 5-fold more active than 1, respectively, in this assay with less actin binding affinity. Latrunculin A ( 1, IC 50 6.7 microM) and its 17- O-[ N-(benzyl)carbamate ( 6, IC 50 29 microM) suppress hypoxia-induced HIF-1 activation in T47D breast tumor cells.
Phage Particle-Mediated Gene Transfer to Cultured Mammalian Cells (1982)

Recombinant phage particles carrying the thymidine kinase (TK) gene of herpes simplex virus type 1, coprecipitated with calcium phosphate, efficiently transformed mouse Ltk- cells to the TK+ phenotype. The conditions necessary to achieve high efficiency of transfer of the TK gene by phage particle-mediated gene transfer were investigated. Of the parameters examined, the pH of the buffer used for coprecipitation of phage particles with calcium phosphate, the length of time of coprecipitation, and the length of the adsorption period were found to alter the transfer efficiency significantly. The optimal pH was 6.87 at 25 degrees C. The other optimal values for these parameters were as follows: coprecipitation time, 7 to 20 min; adsorption time, 18 to 30 h. Treatment with dimethyl sulfoxide, glycerol, or sucrose did not enhance gene transfer. The optimal conditions yielded about 1 transformant per 10(5) phage particles per 10(6) cells without carrier DNA. An increase in the dosage of phage particles, up to at least 5 x 10(7) phage particles per 100-mm dish, resulted in a linear increase in the number of transformants. Addition of carrier phage, up to 10(10) phage particles per dish, did not significantly affect the number of transformants.
ACAT Inhibitors: Potential Anti-atherosclerotic Agents (1994)

Abstract: The evolution of ACAT inhibitors •from purely hypocholestero­ lemic agents to potential anti-atherosclerdtic agents has occurred only recently.A large number of structurally diverse ACAT inhibitors were initially developed as hypocholesterolemic agets whose prime mechanism of action was inhibition of dietary cholesterol absorption in the intestine, however, efficacy for such non-absorbable agents, in humans, has remained elusive. Esterification of cholesterol within the hepatocyte has been shown to be required for VLDL synthesis and secretion, and inhibition of ACAT within the artery wall may prove to be the "ultimate" anti-atherosclerotic mechanism by preventing the formation of cholesterol ester loaded macrophages (foam cells), the precursors of the fatty streak, an early lesion in the atherosclerotic process. Thus, more recently, there has been a concerted effort to design more bioavailable inhibitors capable of inhibiting the enzyme in the liver and artery wall. Displaying direct efficacy at the artery wall for an ACAT inhibitor has been complicated by the fact that in pre-clinical animal models, it has been difficult to dissociate the effects of lipid lowering from a true direct effect at the artery wall. Recently, a novel ACAT inhibitor, Cl-976, has been disclosed which displays anti-atherosclerotic activity in an injured cholesterol fed rabbit model of atherosclerosis without exhibiting a cholesterol lowering effect.The SAR around Cl-976 and related series will be discussed and placed in context with other novel structural types of ACAT inhibitors appearing in the recent literature.
Molecular Diagnosis of the Inherited Long-QT Syndrome in a Woman Who Died after Near-Drowning (1999)

Drowning accounts for more accidental deaths in children and adolescents than all other causes except motor vehicle accidents.1–3 Many of these fatalities are attributed to lack of supervision, trauma, alcohol or drug use, or seizures. However, an appreciable number of drownings have no satisfactory explanation. In these situations, cardiac arrhythmias, particularly those associated with the long-QT syndrome, may be an important consideration. The long-QT syndrome comprises a group of genetically distinct arrhythmogenic cardiovascular disorders, each resulting from a mutation in one of five genes encoding cardiac ion channels or auxiliary ion-channel subunits: KVLQT1 (at the LQT1 locus), HERG (at . . .
A Complete Sequence of the T. tengcongensis Genome (2002)

Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic eubacterium that was isolated from a freshwater hot spring in Tengchong, China. Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an isolate, MB4(T) (Genbank accession no. AE008691). The genome encodes 2588 predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified according to homology to other documented proteins, and the rest, 824 CDS (31.8%), are functionally unknown. One of the interesting features of the T. tengcongensis genome is that 86.7% of its genes are encoded on the leading strand of DNA replication. Based on protein sequence similarity, the T. tengcongensis genome is most similar to that of Bacillus halodurans, a mesophilic eubacterium, among all fully sequenced prokaryotic genomes up to date. Computational analysis on genes involved in basic metabolic pathways supports the experimental discovery that T. tengcongensis metabolizes sugars as principal energy and carbon source and utilizes thiosulfate and element sulfur, but not sulfate, as electron acceptors. T. tengcongensis, as a gram-negative rod by empirical definitions (such as staining), shares many genes that are characteristics of gram-positive bacteria whereas it is missing molecular components unique to gram-negative bacteria. A strong correlation between the G + C content of tDNA and rDNA genes and the optimal growth temperature is found among the sequenced thermophiles. It is concluded that thermophiles are a biologically and phylogenetically divergent group of prokaryotes that have converged to sustain extreme environmental conditions over evolutionary timescale.
Ultrasonic Manipulation of Single Cells (2012)

Ultrasonic manipulation has emerged as a simple and powerful tool for trapping, aggregation, and separation of cells. During the last decade, an increasing amount of applications in the microscale format has been demonstrated, of which the most important is acoustophoresis (continuous acoustic cell or particle separation). Traditionally, the technology has proven to be suitable for treatment of high-density cell and particle suspensions, where large cell and particle numbers are handled simultaneously. In this chapter, we describe how ultrasound can be combined with microfluidics and microplates for particle and cell manipulation approaching the single-cell level. We demonstrate different cell handling methods with the purpose to select, trap, aggregate, and position individual cells in microdevices based on multifrequency ultrasonic actuation, and we discuss applications of the technology involving immune cell interaction studies.
Complications with diabetes (2009)

Poorly controlled diabetes can lead to many complications. Acute complications are.
Silicatein filaments and subunits from a marine sponge direct the polymerization of silica and silicones in vitro (1999)

Nanoscale control of the polymerization of silicon and oxygen determines the structures and properties of a wide range of siloxane-based materials, including glasses, ceramics, mesoporous molecular sieves and catalysts, elastomers, resins, insulators, optical coatings, and photoluminescent polymers. In contrast to anthropogenic and geological syntheses of these materials that require extremes of temperature, pressure, or pH, living systems produce a remarkable diversity of nanostructured silicates at ambient temperatures and pressures and at near-neutral pH. We show here that the protein filaments and their constituent subunits comprising the axial cores of silica spicules in a marine sponge chemically and spatially direct the polymerization of silica and silicone polymer networks from the corresponding alkoxide substrates in vitro, under conditions in which such syntheses otherwise require either an acid or base catalyst. Homology of the principal protein to the well known enzyme cathepsin L points to a possible reaction mechanism that is supported by recent site-directed mutagenesis experiments. The catalytic activity of the "silicatein" (silica protein) molecule suggests new routes to the synthesis of silicon-based materials.
Intraprocedural fusion of electroanatomical maps (EAM) with imaging data based on rapidly-sampled volumetric point clouds from continuous EAM catheter tracking (2007)

Image-guided therapy for electrophysiology applications requires integration of pre-procedural volumetric imaging data with intra-procedural electroanatomical mapping (EAM) information. Existing methods for fusion of EAM and imaging data are based on fiducial landmark identification or point-to-surface distance minimization algorithms, both of which require detailed EAM mapping. This mapping procedure requires specific selection of points on the endocardial surface and this point acquisition process is skill-dependent, time-consuming and labor-intensive. The mapping catheter tip must first be navigated to a landmark on the endocardium, tip contact must be verified, and finally the tip location must be explicitly annotated within the EAM data record. This process of individual landmark identification and annotation must be repeated carefully >50 times to define endocardial and other vascular surfaces with sufficient detail for iterated-closest-point (ICP)-based registration. To achieve this, 30-45 minutes of mapping just for the registration procedure can be necessary before the interventional component of the patient study begins. Any acquired EAM point location that is not in contact with the chamber surface can adversely impact the quality of registration. Significantly faster point acquisition can be achieved by recording catheter tip locations automatically and continuously without requiring explicit navigation to and annotation of fiducial landmarks. We present a novel registration framework in which EAM locations are rapidly acquired and recorded in a continuous, untriggered fashion while the electrophysiologist manipulates the catheter tip within the heart. Results from simulation indicate that mean registration errors are on the order of 3-4mm, comparable in magnitude to conventional registration procedures which take significantly longer to perform. Qualitative assessment in clinical data also reflects good agreement with physician expectations.
Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies (2007)

Reactive oxygen species (ROS) are formed in mammalian cells as a consequence of aerobic respiration. Despite multiple conserved redox modulating systems, a given proportion of ROS continuously escape from the mitochondrial respiratory chain, being sufficiently potent to damage cells in various ways, including numerous carcinogenic DNA mutations. Oxidative stress resulting from an imbalanced ratio between ROS production and detoxification may also disturb physiological signal transduction, lead to chain reactions in lipid layers, and damage DNA repair enzymes. The significance of ROS and antioxidant systems in carcinogenesis is still complicated and in many ways contradictory. Enhanced antioxidant mechanisms in tumor cells in vivo have been implicated in chemoresistance and lead to poor prognosis, whereas most in vitro studies have reported tumor-suppressing properties of antioxidant enzymes. The present review aims to clarify the significance of oxidative stress and the role of cell redox state modulating systems in human malignancies in light of the current literature.
Microfabricated Quadrupole Ion Trap for Mass Spectrometer Applications (2006)

An array of miniaturized cylindrical quadrupole ion traps, with a radius of 20 microm, is fabricated using silicon micromachining using phosphorus doped polysilicon and silicon dioxide for the purpose of creating a mass spectrometer on a chip. We have operated the array for mass-selective ion ejection and mass analysis using Xe ions at a pressure of 10(-4). The scaling rules for the ion trap in relation to operating pressure, voltage, and frequency are examined.