gebhart/patrepeval huggingface dataset:
Comparison of particle size and encapsulation parameters of three liposomal preparations (1993)

Liposomes can be produced by using various techniques such as mechanical agitation, ultrasonication, ether injection, detergent dialysis, reversed-phase evaporation, extrusion through polycarbonate filters of appropriate pore size, etc. Each procedure provides liposomes with their own perculiar features so the choice of a given one to obtain suitable vesicles for use as drug delivery systems should be based on careful experimentation. In this work we tested three liposome preparation methods that provide unilamellar structures with high yields. In fact, unilamellar vesicles of small diameters (SUV) were prepared by ultrasonication and large unilamellar vesicles (LUV) were obtained by (a) reversed-phase evaporation (REV) and (b) extrusion through polycarbonate filters--with or without preliminary freezing-thawing (VETI and VETII, respectively). According to the results obtained, subsequent filtration of the SUV and REV liposomal preparations results in dramatically decreased average diameters and polydispersity indices, as well as in marked changes in their encapsulation parameters and in lipid losses. Among extruded liposomes, those obtained with preliminary freezing-thawing (VETII) resulted in a higher lipid recovery, even though their average hydrodynamic diameter and polydispersity index as measured by quasi-elastic light-scattering spectroscopy (QELSS) were quite similar to those of the VETI counterparts.
Macrophages as a source of tumoricidal activity (tumor-necrotizing factor) (1980)

Macrophage-enriched peritoneal exudate cells from mice infected with Mycobacterium bovis BCG, macrophage-like tumor cells (PU 5-1.8), and peritoneal macrophages propagated in vitro with macrophage growth factor released tumoricidal activity into the culture medium within 2 to 3 h after stimulation with nanogram quantities of bacterial lipopolysaccharide. The cytotoxic activities from each of the macrophage culture supernatants eluted from diethylaminoethyl-Sephacel columns at a sodium chloride concentration of 200 mM exhibited a molecular weight of 50,000 to 60,000 as estimated by gel filtration, were stable at 56 degrees C for 30 min, and were active at a pH range of 6 to 10. A rabbit antiserum directed against serum-derived cytotoxic activity (tumor-necrotizing factor) from BCG-infected and lipopolysaccharide-challenged mice inhibited all of the cytotoxic activities generated in vitro. This suggests that the macrophage-derived cytotoxins are identical with serum-derived cytotoxic factor, which further implies that the macrophage is the cellular source of tumor-necrotizing factor.
Common cosmetic hydrophilic ingredients as penetration modifiers of flavonoids (2002)

Nowadays, flavonoids are present in many cosmetic formulations, mainly in the form of plant extracts. The main reason of still increasing popularity of these substances is their beneficial biochemical activity. The main factor affecting activity of flavonoids in the skin is their skin penetration ability. The studies have evidenced that flavonoids from grape leaf extract as well as flavonoids like quercetin, rutin and catechin can migrate through the model lipophilic membrane from aqueous solution. The influence of common hydrophilic cosmetic additives on the permeation profile of flavonoids has been checked. The partition coefficients of examined flavonoids in the octanol-water extraction system were determined. Correlations between permeation coefficients and log P of particular flavonoids were plotted. To determine the mechanism of influence of hydrophilic substances on the permeation profile of flavonoids, the solubility of these compounds was investigated. Studies suggest that the presence of hydrophilic additives causes the increase in the flavonoid solubility that decreases the activity of flavonoids in the vehicle. In such a situation, the driving force for the penetration is reduced and the decrease of permeation coefficient can be observed.
Two-photon excited visible fluores-cence of hematoporphyrin and pheophorbide a and in vitro experiments of the photodynamic effect on cultured cancer cells using a Nd:YAG laser (1986)

Photodynamic therapy (PDT) represents a new approach to treatment of a variety of malignant tumors in man and animals.1 A nontoxic photosensitizing drug with fluorescent properties, like the hematoporphyrin derivative (HpD), is first injected systemically. After 2-3 days, this drug exhibits a higher retention in the cancer region than in the surrounding normal tissue. Subsequent irradiation with a proper optical wavelength, mainly red around 630 nm, results in rapid necrosis of the neoplastic tissue.
Ammonium Formate in Organic Synthesis: A Versatile Agent in Catalytic Hydrogen Transfer Reductions (1988)

Applications of ammonium formate in organic synthesis are reviewed. 1. Introduction 2. Reduction of Functional Groups 2.1. Initial Studies 2.2. Azides 2.3. Nitro Groups 2.4. Nitriles 3. Dehalogenation of Aromatic Chlorocarbons 4. Deprotection of Functional Groups 4.1. Deprotection of Polymer and Carbobenzyloxy Group from Protected Peptides 4.2. Deprotection of O-Benzyl Group 5. Regioselective Synthesis of 1-Olefins 6. Miscellaneous Applications and Other Formic Acid Derivatives 7. Conclusion
Electrochemical Characterizations on Si and C-Coated Si Particle Electrodes for Lithium-Ion Batteries (2005)

The understanding of cycling and electrochemical characteristics of Si particle anodes for Li-ion batteries has previously been hindered by very fast capacity fading. Optimizing the electrode architecture to significantly improve its stability up to the charge-discharge level has made it possible to investigate these properties to a greater depth than before. The capacity fading and lithiation mechanisms of Si and C-coated Si particles have been studied in this paper by cycling test and electrochemical impedance spectroscopy (EIS) analysis. The capacity vs cycle number plot exhibits two regions of different fading rates, including an initial region of slow fading followed by accelerated decay. The latter may be associated with large-scale failure of the electrode structure. EIS revealed a core-shell lithiation mechanism of Si. C-coating not only exerts remarkable favorable effects against capacity fading, but also serves as a conduit for Li ions to the reaction with Si particles.
The IL-15Rα Chain Signals Through Association with Syk in Human B Cells (2001)

The alpha-chain of the IL-15R (IL-15Ralpha) serves as the specific, high-affinity receptor for IL-15. It is expressed by lymphoid and nonlymphoid cells, including B cell lymphoma lines. In this study, we have further explored IL-15Ralpha-mediated signaling in activated primary B cells and in Raji cells, a human B-lymphoblastoid cell line which expresses the IL-15Ralpha and IL-2Rgamma chains, but lacks the IL-2Rbeta chain. Stimulation of Raji cells with IL-15 induces their proliferation and rescues them from C2-ceramide-induced apoptosis. By immunoprecipitation and Western blotting, we show that treatment of Raji cells and activated primary B cells with IL-15 induces coprecipitation of Syk kinase with the IL-15Ralpha chain. Upon association, the activated Syk kinase phosphorylates the IL-15Ralpha chain as well as phospholipase Cgamma, which coprecipitates with Syk. Furthermore, transfection of Raji cells with stem-loop Syk antisense oligonucleotides prevents IL-15Ralpha and phospholipase Cgamma phosphorylation as well as the inhibition of apoptosis by IL-15. Mutation of a defined region of the intracellular signaling portion of IL-15Ralpha (Tyr227) abrogates both the IL-15Ralpha/Syk association and IL-15Ralpha phosphorylation. Taken together, this suggests that Syk kinase physically and functionally associates with the IL-15Ralpha chain in B cells and that Syk plays a key role in mediating IL-15-induced signal transduction, thus accounting for the distinct functional consequences of IL-15 vs IL-2 binding to B cells.
Inhibition of Intracellular Antiviral Defense Mechanisms Augments Lentiviral Transduction of Human Natural Killer Cells: Implications for Gene Therapy (2012)

Adoptive immunotherapy with genetically modified natural killer (NK) cells is a promising approach for cancer treatment. Yet, optimization of highly efficient and clinically applicable gene transfer protocols for NK cells still presents a challenge. In this study, we aimed at identifying conditions under which optimum lentiviral gene transfer to NK cells can be achieved. Our results demonstrate that stimulation of NK cells with interleukin (IL)-2 and IL-21 supports efficient transduction using a VSV-G pseudotyped lentiviral vector. Moreover, we have identified that inhibition of innate immune receptor signaling greatly enhances transduction efficiency. We were able to boost the efficiency of lentiviral genetic modification on average 3.8-fold using BX795, an inhibitor of the TBK1/IKKɛ complex acting downstream of RIG-I, MDA-5, and TLR3. We have also observed that the use of BX795 enhances lentiviral transduction efficiency in a number of human and mouse cell lines, indicating a broadly applicable, practical, and safe approach that has the potential of being applicable to various gene therapy protocols.
Kernel Optimizations and Prefetch with the Spike Executable Optimizer (2001)

Spike is an executable optimizer that uses profile information to place application code for improved fetch efficiency and reduced cache footprint. This placement reduces the number of cache misses and the latencies they add to program execution time. This paper presents extensions of Spike to take advantage of three additional performance opportunities: 1) optimization of the Unix kernel code, 2) prefetching to reduce latencies of long latency loads, and 3) prefetching for loads with predictable strides that are not detected at compile-time.
Through-substrate coupling elements for silicon-photonics-based short-reach optical interconnects (2019)

Laser integration and photonics chip packaging are the two key challenges that require attention to drive down the cost/bit metric for silicon photonics based optical interconnects. We try to address the latter by demonstrating optical interfaces that fit well in an overall scheme of 2.5D/3D electro-optic integration needed for a high performance computing environment. A through-substrate coupling interface provides the benefit of bonding a silicon photonic chip face-up on a package substrate such that the device-side of the chip remains accessible for die-stacking and fiber-array packaging, thereby offering a promising alternative to flip-chip based packaging. In this paper, we demonstrate three through-substrate coupling elements to enable alignment tolerant and energy-efficient integration of silicon photonics with board-level or package-level optical interconnects : (i) a downward directionality O-band grating coupler with a peak -2.3 dB fiber-to-silicon waveguide coupling efficiency; (ii) polymer microlenses hybrid integrated onto the substrate of a silicon photonic chip to produce an expanded collimated beam at &lambda;=1310 nm for a distance of more than 600 &mu;m; (iii) a ball lens placed in a through-package via to result in a 14 &mu;m chip-to-package 1-dB lateral alignment tolerance for coupling into a 20&times;24 µm squared cross-section board-level polymer waveguide.
A novel cDNA restores reduced folate carrier activity and methotrexate sensitivity to transport deficient cells. (1994)

Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the isolation and expression of a cDNA clone that restores RFC activity to human breast cancer cells defective in this transporter. The cDNA cancer cells defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa, whose hydropathy plot, resembling those of mammalian sugar transporters, predicts that it may be a member of a superfamily of transporter genes. Transfection of methotrexate-resistant (MTXR) ZR-75-1 cells with an expression vector, pRFC1, that codes for this peptide restores their ability to accumulate methotrexate. Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but is unaffected by folic acid. The increase in methotrexate uptake that is observed in pRFC1-transfected MTXR ZR-75-1 cells reverses their resistance to this antitumor agent.
DNA recombination during PCR (1990)

PCR co-amplification of two distinct HIV1 tat gene sequences lead to the formation of recombinant DNA molecules. The frequency of such recombinants, up to 5.4% of all amplified molecules, could be decreased 2.7 fold by a 6 fold increase in Taq DNA polymerase elongation time. Crossover sites mapped essentially to three discrete regions suggesting specific Taq DNA polymerase pause or termination sites. PCR mediated recombination may be a problem when studying heterogeneous genetic material such as RNA viruses, multigene families, or repetitive sequences. This phenomenon can be exploited to create chimeric molecules from related sequences.
Strong and Sustained Antihypertensive Effect of Small Interfering RNA Targeting Liver Angiotensinogen (2019)

Small interfering RNAs (siRNAs) targeting hepatic angiotensinogen ( Agt) may provide long-lasting antihypertensive effects, but the optimal approach remains unclear. Here, we assessed the efficacy of a novel AGT siRNA in spontaneously hypertensive rats. Rats were treated with vehicle, siRNA (10 mg/kg fortnightly; subcutaneous), valsartan (31 mg/kg per day; oral), captopril (100 mg/kg per day; oral), valsartan+siRNA, or captopril+valsartan for 4 weeks (all groups, n=8). Mean arterial pressure (recorded via radiotelemetry) was lowered the most by valsartan+siRNA (-68±4 mm Hg), followed by captopril+valsartan (-54±4 mm Hg), captopril (-23±2 mm Hg), siRNA (-14±2 mm Hg), and valsartan (-10±2 mm Hg). siRNA and captopril monotherapies improved cardiac hypertrophy equally, but less than the dual therapies, which also lowered NT-proBNP (N-terminal pro-B-type natriuretic peptide). Glomerular filtration rate, urinary NGAL (neutrophil gelatinase-associated lipocalin), and albuminuria were unaffected by treatment. siRNA lowered circulating AGT by 97.9±1.0%, and by 99.8±0.1% in combination with valsartan. Although siRNA greatly reduced renal Ang (angiotensin) I, only valsartan+siRNA suppressed circulating and renal Ang II. This coincided with decreased renal sodium hydrogen exchanger type 3 and phosphorylated sodium chloride cotransporter abundances. Renin and plasma K<sup>+</sup> increased with every treatment, but especially during valsartan+siRNA; no effects on aldosterone were observed. Collectively, these data indicate that Ang II elimination requires >99% suppression of circulating AGT. Maximal blockade of the renin-angiotensin system, achieved by valsartan+siRNA, yielded the greatest reduction in blood pressure and cardiac hypertrophy, whereas AGT lowering alone was as effective as conventional renin-angiotensin system inhibitors. Given its stable and sustained efficacy, lasting weeks, RNA interference may offer a unique approach to improving therapy adherence and treating hypertension.
A strategy for the selection of monovalent antibodies that span protein dimer interfaces (2019)

Ligand-induced dimerization is the predominant mechanism through which secreted proteins activate cell surface receptors to transmit essential biological signals. Cytokines are a large class of soluble proteins that dimerize transmembrane receptors into precise signaling topologies, but there is a need for alternative, engineerable ligand scaffolds that specifically recognize and stabilize these protein interactions. Recombinant antibodies can potentially serve as robust and versatile platforms for cytokine complex stabilization, and their specificity allows for tunable modulation of dimerization equilibrium. Here, we devised an evolutionary strategy to isolate monovalent antibody fragments that bridge together two different receptor subunits in a cytokine-receptor complex, precisely as the receptors are disposed in their natural signaling orientations. To do this, we screened a naive antibody library against a stabilized ligand-receptor ternary complex that acted as a "molecular cast" of the natural receptor dimer conformation. Our selections elicited "stapler" single-chain variable fragments (scFvs) of antibodies that specifically engage the interleukin-4 receptor heterodimer. The 3.1 Å resolution crystal structure of one such stapler revealed that, as intended, this scFv recognizes a composite epitope between the two receptors as they are positioned in the complex. Extending our approach, we evolved a stapler scFv that specifically binds to and stabilizes the interface between the interleukin-2 cytokine and one of its receptor subunits, leading to a 15-fold enhancement in interaction affinity. This demonstration that scFvs can be selected to recognize epitopes that span protein interfaces presents new opportunities to engineer structurally defined antibodies for a broad range of research and therapeutic applications.
Bacterial artificial chromosomes improve recombinant protein production in mammalian cells (2009)

Generation of stable cell clones for protein production using Bacterial Artificial Chromosomes offers a clear advantage over the use of conventional vectors. First, protein production is increased by a factor of 10; second, protein production is stable overtime and third, generation of BAC-based expression vectors does not imply a significant amount of work compare to a conventional vector. Therefore, BAC-based vectors may become an attractive tool for protein production.
Volumes of Individual Amino Acid Residues in Gas-Phase Peptide Ions (1999)

Collision cross section measurements and molecular modeling calculations have been combined to extract average volumes of amino acid residues in gas-phase peptide ions. The approach uses cross sections for a series of 103 lysine-terminated peptide ions having the general form [XxxnLys+H]+ (where Xxx is any amino acid except Lys, Arg, His, and Cys, and n = 4 to 8). The results show that average volumes of individual Xxx residues in the gas phase are 5 to 15% smaller than when found in protein interiors; the Lys residue is 20% smaller in the gas phase than in protein cores. The relatively small volumes of amino acids in the gas phase compared with protein core volumes are explained by considering that few gaps or crevices along interior regions exist in compact model structures that represent the experimental data. The very small volume of the Lys residue in peptide ions is consistent with the expectation that this amino acid is the charge carrier in most (if not all) of the peptides and is subject to “electroconstriction”. Some implications of these results in understanding amino acid packing in gas-phase peptide ions and in protein cores are discussed.
Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part I: Animal Models and Toxicity Assays (2010)

A great number of animal species and models are available that simulate retinal diseases and provide experimental data for further human use. Work with animal models should include properly designed toxicity assays to obtain reliable results for safety and efficacy.
Observations on the Mannich Reaction of Estrone (1962)

A route to 2,4-dimethylestradiol by the Mannich reaction is described. 2-Aziridino methylestrone and 2-(2,2'-dichloroethylarnino)methyl estrone have been prepared.
Inability of Mouse Blastomere Nuclei Transferred to Enucleated Zygotes to Support Development in Vitro (1984)

More than 90 percent of enucleated one-cell mouse embryos receiving pronuclei from other one-cell embryos successfully develop to the blastocyst stage in vitro. In this investigation, nuclei from successive preimplantation cleavage stages were introduced into enucleated one-cell embryos and the embryos were tested for development in vitro. Although two-cell nuclei supported development to the morula or blastocyst stage, four-cell, eight-cell, and inner cell mass cell nuclei did not. The inability of cell nuclei from these stages to support development reflects rapid loss of totipotency of the transferred nucleus and is not the result of simultaneous transfer of membrane or cytoplasm.
Fourier phase microscopy for investigation of biological structures and dynamics (2004)

By use of the Fourier decomposition of a low-coherence optical image field into two spatial components that can be controllably shifted in phase with respect to each other, a new high-transverse-resolution quantitative-phase microscope has been developed. The technique transforms a typical optical microscope into a quantitative-phase microscope, with high accuracy and a path-length sensitivity of lambda/5500, which is stable over several hours. The results obtained on epithelial and red blood cells demonstrate the potential of this instrument for quantitative investigation of the structure and dynamics associated with biological systems without sample preparation.
Circumstances and mechanisms of inhibition of translation by secondary structure in eucaryotic mRNAs. (1989)

This paper describes in vitro experiments with two types of intramolecular duplex structures that inhibit translation in cis by preventing the formation of an initiation complex or by causing the complex to be abortive. One stem-loop structure (delta G = -30 kcal/mol) prevented mRNA from engaging 40S subunits when the hairpin occurred 12 nucleotides (nt) from the cap but had no deleterious effect when it was repositioned 52 nt from the cap. This result confirms prior in vivo evidence that the 40S subunit-factor complex, once bound to mRNA, has considerable ability to penetrate secondary structure. Consequently, translation is most sensitive to secondary structure at the entry site for ribosomes, i.e., the 5' end of the mRNA. The second stem-loop structure (hp7; delta G = -61 kcal/mol, located 72 nt from the cap) was too stable to be unwound by 40S ribosomes, hp7 did not prevent a 40S ribosomal subunit from binding but caused the 40S subunit to stall on the 5' side of the hairpin, exactly as the scanning model predicts. Control experiments revealed that 80S elongating ribosomes could disrupt duplex structures, such as hp7, that were too stable to be penetrated by the scanning 40S ribosome-factor complex. A third type of base-paired structure shown to inhibit translation in vivo involves a long-range interaction between the 5' and 3' noncoding sequences.
Blue photo- and electroluminescence from poly(benzoyl-1,4-phenylene) (1997)

Optical and electroluminescent properties of a new poly(p-phenylene)-type polymer, poly(benzoyl-1, 4-phenylene) (PBP) were studied. PBP is soluble in common organic solvents, has high thermal stability and shows bright blue photoluminescence. Light-emitting diodes fabricated with PBP as the active layer emit blue electroluminescence with a peak wavelength at 446 nm and a brightness of about 100 cd/m2.
Isolation of deoxynivalenol-transforming bacteria from the chicken intestines using the approach of PCR-DGGE guided microbial selection (2010)

The approach with PCR-DGGE guided microbial selection was effective in isolating DON-transforming bacteria and the obtained bacterial isolates were able to transform DON.