gebhart/patrepeval huggingface dataset:
Extensive Survey of Antibody Invariant Positions for Efficient Chemical Conjugation Using Expanded Genetic Codes (2017)

The site-specific chemical conjugation of proteins, following synthesis with an expanded genetic code, promises to advance antibody-based technologies, including antibody drug conjugation and the creation of bispecific Fab dimers. The incorporation of non-natural amino acids into antibodies not only guarantees site specificity but also allows the use of bio-orthogonal chemistry. However, the efficiency of amino acid incorporation fluctuates significantly among different sites, thereby hampering the identification of useful conjugation sites. In this study, we applied the codon reassignment technology to achieve the robust and efficient synthesis of chemically functionalized antibodies containing N<sup>ε</sup>-(o-azidobenzyloxycarbonyl)-l-lysine (o-Az-Z-Lys) at defined positions. This lysine derivative has a bio-orthogonally reactive group at the end of a long side chain, enabling identification of multiple new positions in Fab-constant domains, allowing chemical conjugation with high efficiency. An X-ray crystallographic study of a Fab variant with o-Az-Z-Lys revealed high-level exposure of the azido group to solvent, with six of the identified positions subsequently used to engineer "Variabodies", a novel antibody format allowing various connections between two Fab molecules. Our findings indicated that some of the created Variabodies exhibited agonistic activity in cultured cells as opposed to the antagonistic nature of antibodies. These results showed that our approach greatly enhanced the availability of antibodies for chemical conjugation and might aid in the development of new therapeutic antibodies.
Metabolic clearance and plasma disappearance rates of human pancreatic tumor growth hormone releasing factor in man. (1984)

The metabolic clearance rate (MCR) and plasma disappearance rate (t1/2) of human pancreatic tumor growth hormone releasing factor [hpGRF(1-40)] was determined in normal adult male subjects by single injection and constant infusion techniques. Single injections of 1, 3.3, and 10 micrograms/kg hpGRF(1-40) were administered intravenously, plasma immunoreactive (IR) GRF levels were measured during the subsequent 180 min, and biexponential curve analysis was performed. Graded, dose-constant infusions of hpGRF(1-40) at rates of 1, 3.3, 10, and 33 ng/kg per min were administered and the MCR was calculated from measurement of steady state plasma IR-GRF levels at each infusion rate. The postinfusion disappearance rate was determined by linear regression analysis of plasma IR-GRF levels during the 120-min period after cessation of the infusion. The calculated MCR during the single injection study was 194 +/- 17.5 liters/m2 per d and was not significantly different from the calculated value during the constant infusion study (202 +/- 16 liters/m2 per d). The disappearance rate during the single injection study was subdivided into two linear phases: an initial equilibration phase (7.6 +/- 1.2 min) and a subsequent elimination phase (51.8 +/- 5.4 min). The latter was similar to the linear disappearance rate observed (41.3 +/- 3.0 min) after cessation of the constant infusion. The chromatographic and biologic characteristics of plasma IR-GRF, 30 min after injection, were similar to those of synthetic hpGRF(1-40). The results have been discussed in relation to the MCR of other hypothalamic hormones and have been used to extrapolate secretion rates of GRF in patients with ectopic GRF production.
Modeling of viscous damping of perforated planar microstructures. Applications in acoustics (2004)

The paper contains an analysis of the viscous damping in perforated planar microstructures that often serve as backplates or protecting surfaces in capacitive microsensors. The focus of this work is on planar surfaces containing an offset system of periodic oval holes or its limit cases: a system of circular holes or of slits. The viscous damping is calculated as the sum of squeeze film and the holes' resistances. The optimum number of holes is determined which minimizes the total viscous damping for a given percentage of open area. Graphs and formulas are provided for designing these devices. In the case the open area is higher than 15% the numerical results show that the influence of the holes' geometry (circular or oval) has a slight influence on viscous damping. As the planar structures containing oval holes assure a better protection against dust particles and water drops, they should be preferred in designing protective surfaces for microphones working in a natural environment. The obtained results also can be applied in designing other MEMS devices that use capacitive sensing such as accelerometers, micromechanical switches, resonators, and tunable microoptical interferometers.
Enzymatic Conjugation of Epoxides with Glutathione (1973)

Glutathione epoxide transferase has been isolated in homogeneous form from the livers of male Sprague-Dawley rats. The enzyme is active in the conjugation of glutathione with a large number of compounds bearing an ethylene oxide ring in the terminal portion of an alkyl chain. The enzyme has a molecular weight of 40,000 and is composed of 2 subunits. Several proteins which catalyze the same reaction are demonstrated. Some of these forms, present in the purified enzyme, are interconvertible by freezing and by treatment with ethylenediaminetetraacetate.
Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure (2000)

Mild hypothermia is effective in the prevention of brain edema associated with cerebral ischemia and traumatic brain injury. Brain edema is also a serious complication of acute liver failure (ALF). To assess the effectiveness of hypothermia in ALF, groups of rats were subjected to hepatic devascularization (portacaval anastomosis, followed 48 hours later by hepatic artery ligation), and body temperatures were maintained at either 35 degrees C (hypothermic) or 37 degrees C (normothermic). Mild hypothermia resulted in a significant delay in the onset of severe encephalopathy and in reduction of brain water content compared with normothermic ALF rats (control [n = 8] 80.22%; ALF-37 degrees C [n = 8] 81.74%; ALF-35 degrees C [n = 8] 80.48% [P <.01 compared with ALF-37 degrees C]). This protective effect was accompanied by a significant reduction of cerebrospinal fluid (CSF) (but not plasma) ammonia concentrations (CSF ammonia: control: 0.05 mg/dL; ALF-37 degrees C: 1.01 mg/dL; ALF-35 degrees C: 0.07 mg/dL, P <.01 compared with ALF-37 degrees C). In vivo cerebral microdialysis studies revealed that mild hypothermia resulted in a significant reduction of extracellular glutamate concentrations in the brains of rats with ALF (control: 1. 06 micromol/L; ALF-37 degrees C: 2.74 micromol/L; ALF-35 degrees C: 1.49 micromol/L [P <.01 compared with ALF-37 degrees C]). These findings suggest that: 1) mild hypothermia is an effective approach to the prevention of the central nervous system consequences of experimental ALF; and that 2) the beneficial effect of hypothermia is mediated via mechanisms involving reduced blood-brain transfer of ammonia and/or reduction of extracellular brain glutamate concentrations. Mild hypothermia may be an effective approach to delay the onset of brain edema in patients with ALF awaiting liver transplantation.
Beyond efficacy and safety--the need for convenient and cost-effective iron therapy in health care (2011)

The National Service Framework advocates correction of anaemia in patients with chronic kidney disease (CKD). Oral iron is insufficient, while intravenous (IV) supplementation replenishes and maintains iron stores. Previously, effective delivery of iron therapy using available parenteral preparations has been hampered by dosing schedules and the need in some cases of a test dose. The introduction in Europe of newer iron preparations, including iron isomaltoside 1000 (Monofer) and iron carboxymaltose (Ferinject), now offers a potentially safe, effective and time-efficient method of outpatient iron repletion. This may potentially lead to better cost-effectiveness in a resource-limited service.
Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2'-deoxycytidine. (2002)

Hypermethylation of the promoters of cancer-related genes is often associated with their inactivation during tumorigenesis. Several preclinical and clinical trials have been developed to use DNA methylation inhibitors, such as 5-aza-2'-deoxycytidine (5-Aza-CdR) in attempts to reactivate silenced genes in human cancers. We used high-density oligonucleotide gene expression microarrays to examine the effects of 5-Aza-CdR treatment on human fibroblast cells (LD419) and a human bladder tumor cell line (T24). Data obtained 8 days after recovery from 5-Aza-CdR treatment showed that more genes were induced in tumorigenic cells (61 genes induced; >or=4-fold) than nontumorigenic cells (34 genes induced; >or= 4-fold). Approximately 60% of induced genes did not have CpG islands within their 5' regions, suggesting that some genes activated by 5-Aza-CdR may not result from the direct inhibition of promoter methylation. Interestingly, a high percentage of genes activated in both cell types belonged to the IFN signaling pathway, confirming data from other tumor cell types.
Zone Plate Theory Based on Holography (1967)

A series representation developed from holography theory is used to determine the image distances and relative image intensities for three types of zone plates. The effect of nonlinearity in film reproduction on the hologram of a point object and the images produced by this hologram are discussed.
A novel and stereocontrolled synthesis of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid, a potent broad spectrum β-lactamase inhibitor (1989)

The key step in the preparation of the title compound (BRL 42715) from 6-aminopenicillanic acid was the condensation of the anion, generated by deprotonation of p-methoxybenzyl (5R,6S)-6-bromopenem-3-carboxylate(10), with 1-methyl-1,2,3-triazole-4-carbaldehyde; in situ acylation, followed by reductive elimination afforded the isomeric (Z)- and (E)-6-triazolylmethylene penem esters, (12) and (13) respectively.
Specific Transcription Factors Stimulate Simian Virus 40 and Polyomavirus Origins of DNA Replication (1992)

The origins of DNA replication (ori) in simian virus 40 (SV40) and polyomavirus (Py) contain an auxiliary component (aux-2) composed of multiple transcription factor binding sites. To determine whether this component stimulated replication by binding specific transcription factors, aux-2 was replaced by synthetic oligonucleotides that bound a single transcription factor. Sp1 and T-antigen (T-ag) sites, which exist in the natural SV40 aux-2 sequence, provided approximately 75 and approximately 20%, respectively, of aux-2 activity when transfected into monkey cells. In cell extracts, only T-ag sites were active. AP1 binding sites could replace completely either SV40 or Py aux-2. Mutations that eliminated AP1 binding also eliminated AP1 stimulation of replication. Yeast GAL4 binding sites that strongly stimulated transcription in the presence of GAL4 proteins failed to stimulate SV40 DNA replication, although they did partially replace Py aux-2. Stimulation required the presence of proteins consisting of the GAL4 DNA binding domain fused to specific activation domains such as VP16 or c-Jun. These data demonstrate a clear role for transcription factors with specific activation domains in activating both SV40 and Py ori. However, no correlation was observed between the ability of specific proteins to stimulate promoter activity and their ability to stimulate origin activity. We propose that only transcription factors whose specific activation domains can interact with the T-ag initiation complex can stimulate SV40 and Py ori-core activity.
Achromatic Metasurface Lens at Telecommunication Wavelengths (2015)

Nanoscale optical resonators enable a new class of flat optical components called metasurfaces. This approach has been used to demonstrate functionalities such as focusing free of monochromatic aberrations (i.e., spherical and coma), anomalous reflection, and large circular dichroism. Recently, dielectric metasurfaces that compensate the phase dispersion responsible for chromatic aberrations have been demonstrated. Here, we utilize an aperiodic array of coupled dielectric nanoresonators to demonstrate a multiwavelength achromatic lens. The focal length remains unchanged for three wavelengths in the near-infrared region (1300, 1550, and 1800 nm). Experimental results are in agreement with full-wave simulations. Our findings are an essential step toward a realization of broadband flat optical elements.
Molecular mechanisms of cardiomyocyte aging (2011)

Western societies are rapidly aging, and cardiovascular diseases are the leading cause of death. In fact, age and cardiovascular diseases are positively correlated, and disease syndromes affecting the heart reach epidemic proportions in the very old. Genetic variations and molecular adaptations are the primary contributors to the onset of cardiovascular disease; however, molecular links between age and heart syndromes are complex and involve much more than the passage of time. Changes in CM (cardiomyocyte) structure and function occur with age and precede anatomical and functional changes in the heart. Concomitant with or preceding some of these cellular changes are alterations in gene expression often linked to signalling cascades that may lead to a loss of CMs or reduced function. An understanding of the intrinsic molecular mechanisms underlying these cascading events has been instrumental in forming our current understanding of how CMs adapt with age. In the present review, we describe the molecular mechanisms underlying CM aging and how these changes may contribute to the development of cardiovascular diseases.
Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis (2002)

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (tau=40 ms) versus stable plaques (tau=400 ms) and normal aorta (tau=500 ms) . These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.
Increased Expression of NAPDH Oxidase 4 in Systemic Sclerosis Dermal Fibroblasts: Regulation by Transforming Growth Factor β (2015)

NOX-4 expression and production were found to be constitutively elevated in SSc skin and cultured SSc dermal fibroblasts. TGFβ1 stimulated NOX-4 expression in normal and SSc fibroblasts through PKCδ and Smad2/3 signaling pathways. A small-molecule NOX-4 inhibitor decreased collagen and fibronectin production by normal and SSc fibroblasts, and NOX-4 siRNA knockdown reduced ROS and collagen production by SSc fibroblasts. These results demonstrate the involvement of NOX-4 in SSc-associated fibrosis and indicate NOX-4 inhibitors as novel therapeutic approaches for SSc.
Expression and extracellular release of human immunodeficiency virus type 1 Gag precursors by recombinant baculovirus-infected cells (1992)

The level of synthesis and extracellular release of human immunodeficiency virus type 1 Gag by insect cells was analyzed, using eight different recombinants of Autographa californica nuclear polyhedrosis virus harboring various constructs of the gag gene, cloned under the polyhedrin promoter. The results obtained suggested that gag expression was mainly regulated at the transcriptional level and was not significantly influenced by posttranslational events, e.g., Gag self-assembly, nuclear transport, or extracellular release. Two different forms of Gag were found in the culture medium of recombinant-infected cells. One form consisted of membrane-enveloped, corelike particles released by budding at the plasma membrane; the other of nonparticulate, soluble Gag polyprotein molecules. Both forms coexisted in recombinants expressing Gag with an intact N-terminal myristylation signal, whereas recombinants expressing nonmyristylated Gag released solely the soluble form. This suggested that myristylation of the N terminus was not a prerequisite for efficient extracellular release of Gag by insect cells, which could proceed via two independent but simultaneous mechanisms.
Discovery of a Distinct Superfamily of Kunitz-Type Toxin (KTT) from Tarantulas (2008)

These finding illustrate that the two activity sites of Kunitz-type toxins are functionally and evolutionally independent and provide new insights into effects of Darwinian selection pressures on KTT evolution, and mechanisms by which new functions can be grafted onto old protein scaffolds.
Temporal proteomic profiling of embryonic stem cell secretome during cardiac and neural differentiation (2011)

During recent years, increased efforts have focused on elucidating the pluripotency and self-renewal of stem cells. Differentiation towards the different lineages has attracted significant attention given the potential use of stem cells in regenerative medicine. Embryonic stem cell differentiation is a complex process coordinated by strictly regulated extracellular signals that act in an autocrine and/or paracrine manner. Through secreted molecules, stem cells affect local niche biology and influence the cross-talking with the surrounding tissues. Emerging evidence supports the hypothesis that fundamental cell functions, including proliferation and differentiation, are strictly regulated by the complex set of molecules secreted from cells. The understanding of this molecular language could largely increase our knowledge on pathways regulating stem cell differentiation. Here, we have used a proteomics platform to investigate the profile of proteins secreted during differentiation of murine embryonic stem cells. We have followed the dynamics of protein secretion by comparing the secretomes at different time points of murine embryonic stem cell cardiac and neural differentiation. In addition to previously reported molecules, we have identified many secreted proteins not described so far as released from embryonic stem cells nor shown to be differentially released during the process of cardiomyogenesis and neurogenesis.
Detection and Characterization of Reactive Oxygen and Nitrogen Species in Biological Systems by Monitoring Species-Specific Products (2017)

More work is required to characterize the chemical reactivity of the ROS/RNS probes, and to develop new probes/detection approaches enabling real-time, selective monitoring of the specific products formed from the probes. Antioxid. Redox Signal. 28, 1416-1432.
Stride Characteristics of Overground versus Treadmill Locomotion in the Saddle Horse (1993)

The purpose of this study was to compare the velocity-dependent changes in stride length and stride frequency of horses performing the same incremental exercise test first on a track with a rider and then on a treadmill with a 0 and 3.5% slope successively. Seven French saddle horses undertook the exercise test which consisted of 5 stages of increasing speed for 3 min each with 1 min rest between each stage (1.6, 4.2, 8.3, 9.2 and 10 m/s). The horses were recorded by use of a video camera, and the tapes were analysed with regard to gait parameters. At 1.6, 8.3, 9.2 and 10 m/s, stride frequencies were significantly (p < 0.01) greater on the track than on the treadmill. At the walk, stride length was significantly (p < 0.01) shorter on the track than on the treadmill. There were strong linear relationships between stride length and speed in all experimental conditions (R2 > 0.96). The comparison of the regression coefficients revealed significant differences (p < 0.01) between track and treadmill locomotion; stride length was longer on both the horizontal and inclined treadmill than on the track. The incline of the treadmill did not significantly (p > 0.01) influence stride parameters.
A Comparison of Fuel Distribution and Combustion During Engine Cold Start for Direct and Port Fuel Injection Systems (1999)

&lt;div class="htmlview paragraph"&gt;Experiments have been conducted in a firing single-cylinder spark-ignition engine employing a Ford Zetec cylinder head that has been modified to operate with either standard port-fuel-injection, air-forced port-fuel-injection or direct-injection. The engine utilizes a fused silica cylinder and therefore provides extensive optical access to the combustion chamber. Tests were conducted using a constant speed simulated cold start procedure, which is composed of an initial start-up transient and a quasi-steady-state idle period. In this procedure, the engine is briefly motored at 889 rpm and then combustion commences shortly after the start of fuel injection. Measurements which were performed include in-cylinder pressure as well as intake valve, exhaust valve, piston, cylinder, head, and intake air temperature throughout each cycle of the test period. The engine-out total hydrocarbon emissions were also measured. Engine start quality is quantified by the length of the initial start-up period and the stability of the quasi-steady-state idle. Based on these two parameters, the influence of three fuel injection systems, operating temperature, ignition timing, and injection timing on the engine performance during cold start are presented and discussed. In addition, the pre-combustion fuel distribution is measured using two-dimensional laser-induced fluorescence. The pre-combustion fuel distribution images of the three injection systems at different crank angles and times during the test are presented and discussed relative to engine performance.&lt;/div&gt;
Animal models of nociception. (2001)

The study of pain in awake animals raises ethical, philosophical, and technical problems. We review the ethical standards for studying pain in animals and emphasize that there are scientific as well as moral reasons for keeping to them. Philosophically, there is the problem that pain cannot be monitored directly in animals but can only be estimated by examining their responses to nociceptive stimuli; however, such responses do not necessarily mean that there is a concomitant sensation. The types of nociceptive stimuli (electrical, thermal, mechanical, or chemical) that have been used in different pain models are reviewed with the conclusion that none is ideal, although chemical stimuli probably most closely mimic acute clinical pain. The monitored reactions are almost always motor responses ranging from spinal reflexes to complex behaviors. Most have the weakness that they may be associated with, or modulated by, other physiological functions. The main tests are critically reviewed in terms of their sensitivity, specificity, and predictiveness. Weaknesses are highlighted, including 1) that in most tests responses are monitored around a nociceptive threshold, whereas clinical pain is almost always more severe; 2) differences in the fashion whereby responses are evoked from healthy and inflamed tissues; and 3) problems in assessing threshold responses to stimuli, which continue to increase in intensity. It is concluded that although the neural basis of the most used tests is poorly understood, their use will be more profitable if pain is considered within, rather than apart from, the body's homeostatic mechanisms.