gebhart/patrepeval huggingface dataset:
A single H:CDR3 residue in the anti-digoxin antibody 26-10 modulates specificity for C16-substituted digoxin analogs (2001)

We constructed Fab libraries of bacteriophage-displayed H:CDR3 mutants in the high-affinity anti-digoxin antibody 26-10 to determine structural constraints on affinity and specificity for digoxin. Libraries of mutant Fabs randomized at five or 10 contiguous positions were panned against digoxin and three C16-substituted analogs, gitoxin (16-OH), 16-formylgitoxin and 16-acetylgitoxin. The sequence data from 83 different mutant Fabs showed highly restricted consensus patterns at positions H:100, 100a and 100b for binding to digoxin; these residues contact digoxin in the 26-10:digoxin co-crystal structure. Several mutant Fabs obtained following panning on digoxin-BSA showed increased affinity for digoxin compared with 26-10 and retained the wild-type (wt) Trp at position 100. Those Fabs selected following panning on C16-substituted analogs showed enhanced binding to the analogs. Replacement of H:Trp100 by Arg resulted in mutants that bound better to the analogs than to digoxin. This specificity change was unexpected, as C16 lies on the opposite side of digoxin from H:CDR3. Substitution of wt Trp by Arg appears to alter specificity by allowing the hapten to shift toward H:CDR3, thereby providing room for C16 substituents in the region of H:CDR1.
Effect of Escherichia coli L-form cytoplasmic membranes on the interaction between macrophages and Lewis lung carcinoma cells: scanning electron microscopy (1997)

Scanning electron microscopy (SEM) investigations on the interactions between peritoneal macrophages from Lewis lung carcinoma (LLC)-bearing mice and LLC tumour cells during 21 days after tumour implantation were carried out. The action of lipopolysaccharide (LPS)-containing cytoplasmic membranes (CM), from the stable protoplast type L-form of Escherichia coli, on the activity of in vitro phagocytosis was studied; CM induced a continuous increase in macrophage numbers. Activation of macrophage surfaces in healthy and tumour-bearing mice was established. Lamelipods, pseudopods and migration fringes 14 days after CM application were seen. Crater-like cavities deeply in the macrophage cells as well as adherent or prominent engulfed tumour cells within macrophages were observed during in vitro interaction with LLC cells. Macrophages from tumour-bearing mice without CM treatment showed less activation evaluated by SEM during earlier stages of tumour growth. The SEM investigation proved the temporary stimulating effect of E. coli L-form CM on the cell surface activation of peritoneal macrophages in healthy and LLC-bearing mice.
Listeriolysin O Potentiates Immunotoxin and Bleomycin Cytotoxicity (1997)

Antitumor immunotoxins were formed by covalently attaching the ribosome-inactivating protein ricin A chain (RA) to the antitumor antibodies BR96 and L6. In vitro cytotoxicity assays established that BR96-RA was cytotoxic to H2987 human lung adenocarcinoma cells (IC50 = 6 nM), while L6-RA exhibited very low levels of cytotoxic activity (18% cell kill at 67 nM). The virulence factor from the intracellular pathogen Listeria monocytogenes, listeriolysin O (LLO), was able to potentiate the cytotoxicity of BR96-RA and L6-RA by 120- and > 1340-fold, respectively, resulting in IC50 values of approximately 50 pM. LLO also potentiated the cytotoxicity of the peptide anticancer drug bleomycin by a factor of > 2500 but had no effect on the cytotoxic activities of the anticancer drugs cytarabine and etoposide phosphate. In addition, LLO did not potentiate the cytotoxic activity of unconjugated ricin A chain or L6-RA on H2987 cells that were saturated with L6 prior to conjugate treatment. These results are attributed to LLO-induced alteration of the intracellular trafficking of molecules that are incorporated into acidic vesicles.
Signaling Through Platelet Integrin αIIbβ3: Inside-out, Outside-in, and Sideways (1999)

Introduction Cell adhesion, which plays a major role in the response of tissues to injury, involves a wide variety of cells, adhesion receptors, and ligands. Prominent among the cells responding to injury are platelets, the first line of defense against hemorrhage and an early player in the overall process of wound-healing.1 Prominent among the adhesion receptors is αIIbβ3, a platelet-specific integrin essential for hemostasis by virtue of its role in mediating platelet aggregation and platelet spreading on vascular matrices. Prominent among the ligands for αIIbβ3 are the multivalent adhesive proteins, fibrinogen and von Willebrand factor (vWF), which in soluble form, mediate platelet aggregation and, in solid phase, mediate adhesive spreading.2 In addition to the adhesive functions of αIIbβ3, this integrin serves as a bidirectional conduit for biochemical and mechanical information flow across the platelet plasma membrane.3 For example, intracellular signals modulate the ligand-binding function of αIIbβ3 (inside-out signaling), and signals generated by ligation and clustering of αIIbβ3 regulate the extent of platelet aggregation and spreading (outside-in signaling). The relationships between αIIbβ3 and intracellular signaling pathways have been the subject of intense study in human platelets, model cell systems, and more recently, in genetically-modified mice. Although model cells and mouse platelets have become indispensable tools to dissect mechanisms of αIIbβ3 signaling, conclusions drawn from their use must always be validated in human platelets. Despite this caveat, a broad, but still incomplete, picture of integrin signaling in platelets is beginning to emerge. This update will highlight selected recent developments in this area and discuss potential clinical implications.
Electrical Stimulation for Wound Healing: A Review of Evidence From In Vitro Studies, Animal Experiments, and Clinical Trials (2005)

This article reviews theories linked to endogenous bioelectric currents and the role they may play in wound repair with further appraisal of in vitro and in vivo research related to the effects of clinically applicable electrical currents on protein synthesis, cell migration, and antibacterial outcomes. In addition, studies on the effects of electrical stimulation (ES) on skin grafts, donor sites, and musculocutaneous flaps in animals are evaluated, as well as assessments of numerous clinical reports that examined the effects of ES on angiogenesis, perfusion, PtcO2, and epithelialization. Finally, a plethora of clinical trials related to the responses of chronic lower extremity wounds to ES therapy are reviewed, with emphasis on wounds caused by venous insufficiency, diabetic neuropathy, and ischemia in patients with and without diabetes mellitus. A glossary that addresses ES terminology is also included.
Streak growth and breakdown in a boundary layer with steady uniform suction (2004)

Turbulent flow processes play an important role in many flow systems. To optimize and control energy losses of such systems, knowledge of the mechanisms leading to and maintaining turbulence is required. Steady, uniform suction through porous materials is one control method known to stabilize the flat plate boundary layer flow. As wall suction is applied, the growth of Tollmien-Schlichting waves are decreased and a critical Reynolds number of 54000 is reported 1 . Wind tunnel experiments show that also disturbances arising due to free stream turbulence are dampened by wall suction 23 . A common observation for parallel shear flows, and boundary layers in particular, is that streamwise streaks pre-date transition to turbulence 4 .T hus a numerical study of streak instabilities and breakdown is a natural step in elucidating the stabilizing effects of wall suction. In this work, several scenarios of breakdown to turbulence of a flat plate boundary layer with wall suction is studied. Calculations have been performed by means of direct simulations of the Navier-Stokes equations in the temporal domain. This approach allow for the study of the evolution of periodic disturbances such as streaks and oblique waves found in figure 1. The studied disturbances are found to trigger transition to turbulence by similar mechanisms as other flows. Energy thresholds for transition to turbulence is calculated and transition at the lowest energy is provided by the oblique wave scenario for all investigated Reynolds numbers. The next step of the investigation is to study the flow further into the turbulent state, which requires the simulation code to be run in a spatial setup.
Nitrate and nitrite in foods and the diet (1994)

Concentrations of nitrate and nitrite have been determined in a range of foods and the dietary intake estimated from the MAFF Total Diet Study. The estimated dietary intake of nitrate ion for the UK population was 54 mg/day and the estimated dietary intake of nitrite ion was in the range 2.4-4.2 mg/day in 1985. The main source of nitrate in the diet is from the consumption of vegetables.
Clostridium difficile toxin B is more potent than toxin A in damaging human colonic epithelium in vitro. (1995)

Toxin A but not toxin B, appears to mediate intestinal damage in animal models of Clostridium difficile enteritis. The purpose of this study was to investigate the electrophysiologic and morphologic effects of purified C. difficile toxins A and B on human colonic mucosa in Ussing chambers. Luminal exposure of tissues to 16-65 nM of toxin A and 0.2-29 nM of toxin B for 5 h caused dose-dependent epithelial damage. Potential difference, short-circuit current and resistance decreased by 76, 58, and 46%, respectively, with 32 nM of toxin A and by 76, 55, and 47%, respectively, with 3 nM of toxin B, when compared with baseline (P < 0.05). 3 nM of toxin A did not cause electrophysiologic changes. Permeability to [3H]mannitol increased 16-fold after exposure to 32 nM of toxin A and to 3 nM of toxin B when compared with controls (P < 0.05). Light and scanning electron microscopy after exposure to either toxin revealed patchy damage and exfoliation of superficial epithelial cells, while crypt epithelium remained intact. Fluorescent microscopy of phalloidin-stained sections showed that both toxins caused disruption and condensation of cellular F-actin. Our results demonstrate that the human colon is approximately 10 times more sensitive to the damaging effects of toxin B than toxin A, suggesting that toxin B may be more important than toxin A in the pathogenesis of C. difficile colitis in man.
Generalized Semi-Orthogonal Multiple-Access for Massive MIMO (2015)

We propose a novel framework to enable concurrent transmission of multiple users to an access node equipped with a massive multiple-input multiple-output (mMIMO), which encompasses and extends the conventional time-division duplex (TDD) protocol and the recently proposed semi-orthogonal multiple-access (SOMA). The new solution is referred to generalized semi-orthogonal multiple-access (GSOMA). To enable GSOMA, the users are grouped such that the users within each group are assigned mutually orthogonal pilot sequences. However the pilot sequences can be reused in different groups and the users in different group are coordinated such that their pilot sequences do not interfere by a semi-orthogonal mechanism enabled by a resource-offset sequence. We describe the general framework and analyze a case of GSOMA and show that a properly designed GSOMA can outperform the conventional TDD and SOMA.
A Cooperative Approach to Particle Swarm Optimization (2004)

The particle swarm optimizer (PSO) is a stochastic, population-based optimization technique that can be applied to a wide range of problems, including neural network training. This paper presents a variation on the traditional PSO algorithm, called the cooperative particle swarm optimizer, or CPSO, employing cooperative behavior to significantly improve the performance of the original algorithm. This is achieved by using multiple swarms to optimize different components of the solution vector cooperatively. Application of the new PSO algorithm on several benchmark optimization problems shows a marked improvement in performance over the traditional PSO.
Unidirectional Side Scattering of Light by a Single-Element Nanoantenna (2013)

Unidirectional side scattering of light by a single-element plasmonic nanoantenna is demonstrated using full-field simulations and back focal plane measurements. We show that the phase and amplitude matching that occurs at the Fano interference between two localized surface plasmon modes in a V-shaped nanoparticle lies at the origin of this effect. A detailed analysis of the V-antenna modeled as a system of two coherent point-dipole sources elucidates the mechanisms that give rise to a tunable experimental directivity as large as 15 dB. The understanding of Fano-based directional scattering opens a way to develop new directional optical antennas for subwavelength color routing and self-referenced directional sensing. In addition, the directionality of these nanoantennas can increase the detection efficiency of fluorescence and surface enhanced Raman scattering.
Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways (2013)

The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2'-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.
Weak elastic anisotropy (1986)

Abstract Most bulk elastic media are weakly anisotropic. The equations governing weak anisotropy are much simpler than those governing strong anisotropy, and they are much easier to grasp intuitively. These equations indicate that a certain anisotropic parameter (denoted delta ) controls most anisotropic phenomena of importance in exploration geophysics, some of which are nonnegligible even when the anisotropy is weak. The critical parameter delta is an awkward combination of elastic parameters, a combination which is totally independent of horizontal velocity and which may be either positive or negative in natural contexts.
Macromolecular Complexation between Bovine Serum Albumin and the Self-Assembled Hydrogel Nanoparticle of Hydrophobized Polysaccharides (1996)

Macromolecular complexation between bovine serum albumin (BSA) and self-assembled hydrogel nanoparticle formed by the self-aggregation of cholesterol-bearing pullulan (CHP) was studied by high performance size exclusion column chromatography (HPSEC) and circular dichroism (CD). The CHP self-aggregates complexed with one BSA molecule to give colloidally stable nanoparticles (RG = 17 nm) at pH 7.0 and 25 °C. This was almost irrespective of the substitution degree of the cholesterol group of CHP. The helical content of BSA decreased upon complexation. Unfolding of BSA by either heating or a denaturant such as urea was largely suppressed upon complexation. BSA would be incorporated inside into the hydrogel matrix of the CHP nanoparticle. Kinetic analysis of the complexation suggested a two-step process: namely, the fast pre-equilibrium of looser binding of BSA to the CHP self-aggregate followed by the slower process of tighter inclusion into the hydrogel network. The substitution degree of the cholesterol group in CHP significantly affected the complexation kinetics.
Heparin stimulates the synthesis and modifies the sulfation pattern of heparan sulfate proteoglycan from endothelial cells (1989)

Heparin stimulates 2-3-fold, in a concentration-dependent manner, the synthesis of heparan sulfate secreted by cultured endothelial cells. The increase in synthetic rate takes place immediately after exposure of the cells to heparin, affects only heparan sulfate, and is specific for the endothelial cell. No stimulation by other glycosaminoglycans was observed. Analysis of the disaccharide products formed by the action of heparitinases reveals a higher degree of sulfation of the uronic acid residues in the heparan sulfate of cells exposed to heparin.
Effects of three alkoxypsoralens on voltage gated ion channels in Ranvier nodes. (2000)

The effects of the phototoxic K+- channel blockers 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP) on Ranvier nodes were compared to those of 5,8-diethoxypsoralen (5,8-EOP) by means of the Hodgkin-Huxley formalism. When these test substances were added individually to the bathing solution (8-MOP: 100 micromol/l; 5-MOP: 50 micromol/l; 5,8-EOP: 10 micromol/l) the following completely reversible effects were observed: 1. 8-MOP, caused a nearly potential-independent decrease of the sodium permeability, P'Na, by ca. 17%. 5-MOP and 5,8-EOP merely decreased the maximal value of P'Na, by ca. 12 and 8% respectively, whereas with weak depolarisations P'Na was unchanged. 2. In the tested potential range the potassium permeability, P'K, was caused to decrease by ca. 9% by 8-MOP, ca. 21% by 5-MOP and ca. 19% by 5,8-EOP. 3. The potassium currents acquired a phasic time course previously described for 8-MOP and 5-MOP. They reached a relative maximum and approached a lower steady-state value, kinfinity, with a time constant tauk at V = 120 mV of about 16 ms (8-MOP), 20 ms (5-MOP) and 94 ms (5,8-EOP). To obtain dose-response relations the drug-induced effects on peak P'K and on the steady state value, kinfinity, were measured. The corresponding apparent dissociation constants (in micromol/l) were 66.6 and 80.1 (for 8-MOP), 87.6 and 25.8 (for 5-MOP), and 13.5 and 6.5 (for 5,8-EOP). In view of the similarity of the actions of 5-MOP and 5,8-EOP as well as the fact that 5,8-EOP is not phototoxic, in future 5,8-EOP may well prove to be a particularly suitable K+-channel blocker for the symptomatic therapy of multiple sclerosis and other demyelinating diseases.
Tn5 in Vitro Transposition (1998)

This communication reports the development of an efficient in vitro transposition system for Tn5. A key component of this system was the use of hyperactive mutant transposase. The inactivity of wild type transposase is likely to be related to the low frequency of in vivo transposition. The in vitro experiments demonstrate the following: the only required macromolecules for most of the steps in Tn5 transposition are the transposase, the specific 19-bp Tn5 end sequences, and target DNA; transposase may not be able to self-dissociate from product DNAs; Tn5 transposes by a conservative "cut and paste" mechanism; and Tn5 release from the donor backbone involves precise cleavage of both 3' and 5' strands at the ends of the specific end sequences.
Tissue-specific Expression of Sialyltransferases (1989)

Three sialyltransferases which attach terminal sialic acids to glycoprotein sugar chains are shown to exhibit striking differential expression in seven tissues of the rat. Using cDNA probes for the Gal beta 1,4GlcNAc alpha-2,6-sialytransferase which forms a NeuAc alpha 2-6Gal beta 1-4GlcNAc sequence on N-linked sugar chains, three different sized mRNAs are detected, two of which (4.7 and 4.3 kilobases (kb] have high homology along the full length, and a third (3.6 kb, in kidney) which is missing the 5' region corresponding to 45% of the NH2-terminal coding sequence. The 4.7- and 4.3-kb mRNAs exhibit differential expression of over 50-fold with the highest levels in liver and lowest in brain and heart. Assays for enzyme activity in tissue homogenates show high correspondence to the levels of mRNA. Evidence of tissue-specific expression was also obtained for two other sialyltransferases which form the NeuAc alpha 2-3Gal beta 1-4/3GlcNAc and NeuAc alpha 2-3Gal beta 1-3GalNAc sequences on N-linked and O-linked sugar chains, respectively. Comparison of the ratios of the three enzymes in several tissues suggests that they are expressed independently. The results are discussed for their relevance to cellular control of terminal glycosylation sequences on glycoproteins and glycolipids.
Endothelial cell vehicles for delivery of cytotoxic genes as a gene therapy approach for carcinoma of the ovary. (1998)

Human umbilical vein endothelial cells (HUVECs) were evaluated for utility as a vector to achieve a bystander effect and killing of ovarian carcinoma cell lines. After demonstrating that HUVECs could be transduced with the reporter gene LacZ encoded by an adenoviral vector, appropriate cell killing of the AdCMVHSV-TK-transduced HUVECs was exhibited after treatment with 20 microM ganciclovir. Mixing experiments were then performed to determine whether the transduced HUVECs would demonstrate a bystander effect with the ovarian cancer cell lines. When 50% AdCMVHSV-TK-transduced HUVECs were mixed with untransduced ovarian cancer cells, > 70% of all cells were killed. Finally, s.c. and i.p. injections of herpes simplex-thymidine kinase-expressing HUVECs and SKOV3ip1 tumor cells were performed to evaluate the effects of HUVECs in in vivo models. These studies showed a decrease in tumor growth s.c. as well as a statistically significant survival prolongation (P < 0.05) in the i.p. model. These findings suggest that endothelial cells may be used as a vehicle for the delivery of cytotoxicity (bystander effect) in molecular chemotherapy.
Advances in nucleoside monophosphate prodrugs as anti-HCV agents (2010)

Nucleoside monophosphate prodrugs that are eventually bioconverted to the active nucleoside triphosphate (NTP) offer the potential to deliver increased intracellular NTP levels and/or organ-specific NTP enhancement. There are several classes of monophosphate prodrugs that have been applied to HCV drug discovery, and some of these approaches are currently being evaluated in humans. This review discusses recent advances in monophosphate prodrug approaches to improve oral absorption, stability and pharmacokinetic profile, including their advantages and potential pitfalls.
Playing with Cardiac “Redox Switches”: The “HNO Way” to Modulate Cardiac Function (2011)

The nitric oxide (NO(•)) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO(•) as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its "thiophylic" nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure.