gebhart/patrepeval huggingface dataset:
Ge instability and the growth of Ge epitaxial layers in nanochannels on patterned Si (001) substrates (2010)

We report the Ge thermal instability against surface diffusion in extremely narrow channels isolated by SiO2 and demonstrate the selective growth of strain-relaxed Ge epitaxial layers in channels as narrow as 10 nm on patterned Si (001) substrates by a combination of low temperature growth and selective recrystallization using Ge melt and regrowth during a millisecond laser anneal. Filling narrow channels at high growth temperatures is prohibited by Ge outdiffusion due to the high Ge chemical potential in such narrow channels. The Ge thermal instability depends on the channel width and a critical channel width of 50 nm is extracted from our calculation and experimental results. The Ge surface diffusion rate is dominated by the surface diffusion activation energy barrier that is significantly enhanced by the adsorbed surface hydrides. At a low temperature below 450 °C, a hydride-terminated surface is maintained which increases the Ge surface diffusion barrier and retards the outdiffusion of the Ge adatoms, providing excellent channel filling. The resulting low crystalline quality can be restored with a millisecond laser melt and regrowth.
Adsorption of Semiflexible Polyelectrolytes on Charged Planar Surfaces:  Charge Compensation, Charge Reversal, and Multilayer Formation (1999)

We study theoretically the adsorption of semiflexible charged polymers on an oppositely charged flat substrate. We restrict ourselves to polymers with relatively high line charge density τ and bare bending stiffness 𝓁0, such as DNA or fully charged synthetic polyelectrolytes, for which the condition τ2𝓁B𝓁0 > 1 (with 𝓁B = e2/4πεkBT denoting the Bjerrum length) is satisfied. In this case the effective bending rigidity (which includes chain stiffening due to electrostatic monomer−monomer repulsion) is always larger than the screening length, and we obtain very thin adsorption layers, where the polymers essentially lie flat on the surface and can be considered as a two-dimensional layer. We distinguish different adsorbed phases, including a two-dimensional lamellar phase where the polymers run parallel and do not overlap and a disordered phase where the polymers form a random network with multiple crossings. By explicitly including lateral correlations within the adsorbed layer, we find a regime of strong charge reversal, where the adsorbed phase exhibits a much higher surface charge density than the substrate and thus reverses the charge of the substrate by a factor much larger than unity. This charge-reversed regime is characterized by a typical distance between polymers larger than the screening length. We explicitly take image charge effects due to a dielectric jump at the substrate surface and the impenetrability of the substrate for salt ions into account. These effects lead to an increase of the electrostatic persistence length close to the substrate and inhibit adsorption for strongly charged polymers and low-dielectric substrates. At the end, we present some scaling arguments for the formation of charge-oscillating multilayers.
Hormonal control of the cervix in pregnant gilts. IV. Relaxin promotes changes in the histological characteristics of the cervix that are associated with cervical softening during late pregnancy in gilts (1993)

We recently described relaxin-induced changes that occur in both the physical properties and the biochemical composition of the uterine and vaginal portions of the cervix during the last third of gestation in the gilt. This study employed morphometric analysis to examine both the changes that occur in the histological characteristics of the uterine and vaginal portions of the cervix between days 80 and 110 of pregnancy in intact gilts and the effects of relaxin on these changes in ovariectomized gilts given progesterone to maintain pregnancy. There were four treatment groups: intact day 80 control gilts, sham-ovariectomized day 110 control gilts, ovariectomized progesterone-treated day 110 gilts, and ovariectomized progesterone- plus relaxin-treated day 110 gilts. The histological characteristics of the uterine portion of cervices obtained from intact controls on day 110 differed markedly from those of intact controls on day 80; there was a reduction in the density and organization of collagen fiber bundles, a reduction in the density of smooth muscle fiber bundles, and an increase in amorphous ground substance. The histological characteristics of cervices removed on day 110 from ovariectomized gilts given progesterone only did not differ from those of day 80 controls. After replacement therapy with progesterone plus relaxin, however, the histological characteristics of the cervix on day 110 did not differ from those in intact day 110 controls. Additionally, this study demonstrates that the relaxin-dependent changes are more dramatic in the uterine than in the vaginal portion of the cervix. These findings are consistent with and extend our earlier findings that relaxin-dependent changes in the physical properties and biochemical composition of the uterine portion of the cervix far exceed those in the vaginal portion of the cervix during late pregnancy in the gilt. We conclude that the relaxin-dependent changes in the histological characteristics of the cervix described in this report may contribute at least in part to the cervical softening that occurs during late pregnancy in gilts.
Construction and Characterization of a Fusion Protein of Single-Chain Anti-CD20 Antibody and Human β-Glucuronidase for Antibody-Directed Enzyme Prodrug Therapy (1998)

The CD20 antigen is an attractive target for specific treatment of B-cell lymphoma. Antibody-directed enzyme prodrug therapy (ADEPT) aims at the specific activation of a nontoxic prodrug at the tumor site by an enzyme targeted by a tumor-specific antibody such as anti-CD20. We constructed a fusion protein of the single-chain Fv anti-CD20 mouse monoclonal antibody (MoAb) 1H4 and human beta-glucuronidase for the activation of the nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate to doxorubicin at the tumor site. The cDNAs encoding the light- and heavy-chain variable regions of 1H4 were cloned, joined by a synthetic sequence encoding a 15-amino acid linker and fused to human beta-glucuronidase by a synthetic sequence encoding a 6-amino acid linker. An antibody-enzyme fusion protein-producing cell line was established by transfection of the construct into human embryonic kidney 293/EBNA cells. The yield of active fusion protein was 100 ng/mL transfectoma supernatant. Antibody affinity, antibody specificity, and enzyme activity were fully retained by the fusion protein. Immunoprecipitation and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that the fusion protein has a relative molecular weight (Mw) of 100 kD under denaturing conditions. Gel filtration analysis indicated that the enzymatically active form of the fusion protein is a tetramer with an Mw of approximately 400 kD. The nontoxic prodrug N-[4-doxorubicin-N-carbonyl(-oxymethyl) phenyl] O-beta-glucuronyl carbamate was hydrolyzed by the fusion protein at a hydrolysis rate similar to that of human beta-glucuronidase. When the fusion protein was specifically bound to Daudi lymphoma cells, the prodrug induced similar antiproliferative effects as doxorubicin. Thus, it is feasible to construct a eukaryotic fusion protein consisting of a single-chain anti-CD20 antibody and human beta-glucuronidase for future use in the activation of anticancer prodrugs in B-cell lymphoma.
Fully Acid-Degradable Biocompatible Polyacetal Microparticles for Drug Delivery (2008)

A library of polyurethanes and polyureas with different hydrophobicities containing the same acid-degradable dimethyl ketal moiety embedded in the polymer main chain have been prepared. All polymers were synthesized using an AA-BB type step-growth polymerization by reaction of bis(p-nitrophenyl carbamate/carbonate) or diisocyanate monomers with an acid-degradable, ketal-containing diamine. These polymers were designed to hydrolyze at different rates in mildly acidic conditions as a function of their hydrophobicity to afford small molecules only with no polymeric byproduct. The library of polymers was screened for the formation of microparticles using a double emulsion technique. The microparticles that were obtained degraded significantly faster at acidic pH (5.0) than at physiological pH (7.4) with degradation kinetics related to the hydrophobicity of the starting polymer. In vitro studies demonstrated the ability of the FITC-BSA loaded microparticles to be phagocytosed by macrophages resulting in a 10-fold increase in the protein uptake compared to a free protein control; in addition, the microparticles were found to be nontoxic at the concentrations tested of up to 1 mg/mL. The ease of preparation of the polymers coupled with the ability to tune their hydrophobicity and the high acid sensitivity of the microparticles identify this new class of materials as promising candidates for the delivery of bioactive materials.
Mutual passivation of group IV donors and nitrogen in diluted GaNxAs1−x alloys (2003)

We demonstrate the mutual passivation phenomenon of Ge donors and isovalent N in highly mismatched alloy GaNxAs1−x doped with Ge. Layers of this alloy were formed by the sequential implantation of Ge and N ions followed by pulsed laser melting and rapid thermal annealing. The mutual passivation effect results in the electrical deactivation of GeGa donors (Ge on Ga sites) and suppression of the NAs (N on As sites) induced band gap narrowing through the formation of GeGa–NAs nearest neighbor pairs. These results in combination with the analogous effect observed in Si-doped GaNxAs1−x provide clear evidence of the general nature of the mutual passivation phenomenon in highly mismatched semiconductor alloys.
Implementing The Difference-Squared Error Algorithm Using An Acousto-Optic Processor (1989)

Real-time electronic and optical pattern recognition systems use correlation as a means for discriminating objects of interest from unwanted objects and residual clutter in an input scene. However, correlation is not a good technique for certain gray-level input images particularly when the background has a high average value such as encountered in automatic target recognition environments. A better algorithm for these types of environments involves computing the difference-squared error between a reference template and the input image. This algorithm has been used for many years for recognizing gray-level images; however, because of the large number of bits of precision required to perform these computations, the algorithm is difficult to implement in real-time using an electronic embedded computer where small size and low power are at a premium. This paper describes a method for implementing the difference-squared algorithm on an acousto-optic time-integrating correlator. This implementation can accommodate the high dynamic range requirement which is inherent in gray-scale recognition problems. The acousto-optic correlator architecture is a natural fit for this implementation because of its capability to perform two-dimensional processing utilizing relatively mature one-dimensional input devices. Furthermore, since this architecture uses an electronically stored reference, rotational and scale variances can be accommodated by rapidly searching through a library of templates, as first described by Psaltis2. The ability to implement the difference-squared algorithm in an acousto-optic correlator architecture has the potential for solving many practical target recognition problems where real-time discrimination of gray-level objects using a compact, low power processor is required.
Novel 10β-aziridinyl steroids; inhibitors of aromatase (1993)

The novel 10β-aziridinylestr-4-ene-3,17-diones 17 and 18 and the corresponding 10β-aziridinyl-β-hydroxyestr-4-en-3-ones 19 and 20 have been synthesized from the 19-oximino-19-methyl intermediate 12b. The key reaction was the conversion of the 19-oxime 12b into the diastereoisomeric 1OR-aziridines 13 and 14 by lithium aluminium hydride (LAH). Compounds 17–20 are powerful and stereoselective inhibitors of human placental microsomal aromatase. The most potent compound was 17(Ki = 3.4 nmol dm–3). The 19R- isomers 17 and 19 are more effective than the corresponding 19S-isomers 18 and 20, respectively. Unlike the corresponding 10β-oxiranes and -thiiranes which are classical competitive inhibitors, the (19R)-aziridines 17 and 19 appear to be slow-binding inhibitors. Spectroscopic studies with microsomal aromatase preparations indicate that the inhibition process involves binding of aziridine nitrogen to the heme-iron of the enzyme.
Poly(A)-binding protein interaction with elF4G stimulates picornavirus IRES-dependent translation. (2001)

The eukaryotic mRNA 3' poly(A) tail and the 5' cap cooperate to synergistically enhance translation. This interaction is mediated, at least in part, by elF4G, which bridges the mRNA termini by simultaneous binding the poly(A)-binding protein (PABP) and the cap-binding protein, elF4E. The poly(A) tail also stimulates translation from the internal ribosome binding sites (IRES) of a number of picornaviruses. elF4G is likely to mediate this translational stimulation through its direct interaction with the IRES. Here, we support this hypothesis by cleaving elF4G to separate the PABP-binding site from the portion that promotes internal initiation. elF4G cleavage abrogates the stimulatory effect of poly(A) tail on translation. In addition, translation in extracts in which elF4G is cleaved is resistant to inhibition by the PABP-binding protein 2 (Paip2). The elF4G cleavage-induced loss of the stimulatory effect of poly(A) on translation was mimicked by the addition of the C-terminal portion of elF4G. Thus, PABP stimulates picornavirus translation through its interaction with elF4G.
Phase I Clinical Trial of IPI-504, a Novel, Water-Soluble Hsp90 Inhibitor, in Patients with Relapsed/Refractory Multiple Myeloma (MM). (2005)

Abstract IPI-504 is a novel, water-soluble Heat Shock Protein 90 (Hsp90) inhibitor. It is the chemical reduction product of 17-AAG, a well-characterized Hsp90 inhibitor. 17-AAG is currently in clinical trials, but suffers from very poor aqueous solubility and must be administered to patients in either suboptimal DMSO formulations, or newer cremophor or emulsion formulations. IPI-504, however, exists as a hydrochloride salt which is soluble in water in excess of 100 mg/mL. It has previously been shown that IPI-504 inter-converts with 17-AAG and exists in a pH and enzyme-mediated dynamic redox equilibrium. When IPI-504 or 17-AAG is administered to mice, rats, or monkeys a dynamic equilibrium occurs in vivo in which both species are present in plasma as well as tissue. Thus, IPI-504 recapitulates all of the Hsp90 inhibitory properties and biological activity of 17-AAG without its formulation liabilities. In preclinical studies IPI-504 has demonstrated in vitro and in vivo anti-tumor effects in a variety of cancers including xenograft and orthotopic models of multiple myeloma. Therefore an open-label phase I dose-escalation trial of IPI-504 infused on days 1, 4, 8 and 11 of a 21 day cycle is being conducted in pts with relapsed/refractory MM. IPI-504 is infused in 250cc of normal saline over thirty minutes. Pts receive IPI-504 for one cycle of treatment. The primary objectives of the study are to determine the maximum tolerated dose (MTD) and characterize the pharmacokinetic (PK) and pharmacodynamic (PD) marker effects of IPI-504. An accelerated titration design was utilized during the first three dose levels. Dose limiting toxicity (DLT) is defined as grade 4 or greater hematologic toxicity and/or grade 3 or greater non-hematologic toxicity within the first 21 days of treatment. Results demonstrate that the in vivo dynamic equilibrium of IPI-504 and 17-AAG is detectable in human plasma PK samples and the water-based formulation is well-tolerated. Data on PK, dose proportionality, safety, tolerability, PD markers, and anti-tumor activity of IPI-504 will be reported. In conclusion, clinical evaluation of this agent is ongoing to define the safety, tolerability and potential activity of IPI-504 to treat pts with advanced MM. These results may help clarify the effects of Hsp90 inhibition using a water-soluble, ansamycin-based Hsp90 inhibitor without the confounding effects of DMSO-based formulations.
Involvement of PKC‐ι in glioma proliferation (2008)

These results support the concept that presence of PKC-iota may be required for cell proliferation to take place.
Use of DNA barcodes to identify flowering plants (2005)

Methods for identifying species by using short orthologous DNA sequences, known as "DNA barcodes," have been proposed and initiated to facilitate biodiversity studies, identify juveniles, associate sexes, and enhance forensic analyses. The cytochrome c oxidase 1 sequence, which has been found to be widely applicable in animal barcoding, is not appropriate for most species of plants because of a much slower rate of cytochrome c oxidase 1 gene evolution in higher plants than in animals. We therefore propose the nuclear internal transcribed spacer region and the plastid trnH-psbA intergenic spacer as potentially usable DNA regions for applying barcoding to flowering plants. The internal transcribed spacer is the most commonly sequenced locus used in plant phylogenetic investigations at the species level and shows high levels of interspecific divergence. The trnH-psbA spacer, although short ( approximately 450-bp), is the most variable plastid region in angiosperms and is easily amplified across a broad range of land plants. Comparison of the total plastid genomes of tobacco and deadly nightshade enhanced with trials on widely divergent angiosperm taxa, including closely related species in seven plant families and a group of species sampled from a local flora encompassing 50 plant families (for a total of 99 species, 80 genera, and 53 families), suggest that the sequences in this pair of loci have the potential to discriminate among the largest number of plant species for barcoding purposes.
Immunogenic (tum-) variants of mouse tumor P815: cloning of the gene of tum- antigen P91A and identification of the tum- mutation. (1988)

Mutagen treatment of mouse P815 tumor cells produces tum- variants that are rejected by syngeneic mice because these variants express new surface antigens. These "tum- antigens" are recognized by cytolytic T lymphocytes but induce no detectable antibody response. Transfection of P815 cell line P1.HTR with DNA of tum- variant P91 yielded transfectants expressing tum- antigen P91A. They were detected by their ability to stimulate proliferation of cytolytic T lymphocytes [Wölfel, T., Van Pel, A., De Plaen, E., Lurquin, C., Maryanski, J. L. & Boon, T. (1987) Immunogenetics 26, 178-187]. A cosmid library of a cell line expressing antigen P91A was transfected into P1.HTR. Transfectants expressing the antigen were obtained. By packaging directly the DNA of a transfectant with lambda phage extracts, we obtained a small cosmid population containing as major component a cosmid that transferred the expression of P91A. The assay of various restriction fragments of this cosmid led to the isolation of an 800-base-pair fragment containing the P91A sequence required for transfection. Comparison with a homologous cDNA showed that this fragment contained only one of the several exons of the P91A gene. The normal and the tum- forms of the gene differ by one nucleotide located in this 137-base-pair exon. The essential role of this mutation, which produces an amino acid change, was confirmed by site-directed mutagenesis. No significant sequence similarity was found between the 800-base-pair fragment and any recorded gene.
Immunotherapy for Alzheimer’s disease: hoops and hurdles (2013)

Alzheimer's disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide. Currently, there is no cure or way to prevent this devastating disease. Extracellular plaques, containing various forms of amyloid-β protein (Aβ), and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated tau protein, are two major pathological hallmarks of the AD brain. Aggregation, deposition, and N-terminal modification of Aβ protein and tau phosphorylation and aggregation are thought to precede the onset of cognitive decline, which is better correlated with tangle formation and neuron loss. Active and passive vaccines against various forms of Aβ have shown promise in pre-clinical animal models. However, translating these results safely and effectively into humans has been challenging. Recent clinical trials showed little or no cognitive efficacy, possibly due to the fact that the aforementioned neurodegenerative processes most likely pre-existed in the patients well before the start of immunotherapy. Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease. In addition, efforts to immunize against tau and other AD-related targets are underway.
Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors (2003)

Novel nanomaterials for bioassay applications represent a rapidly progressing field of nanotechnology and nanobiotechnology. Here, we present an exploration of single-walled carbon nanotubes as a platform for investigating surface-protein and protein-protein binding and developing highly specific electronic biomolecule detectors. Nonspecific binding on nanotubes, a phenomenon found with a wide range of proteins, is overcome by immobilization of polyethylene oxide chains. A general approach is then advanced to enable the selective recognition and binding of target proteins by conjugation of their specific receptors to polyethylene oxide-functionalized nanotubes. This scheme, combined with the sensitivity of nanotube electronic devices, enables highly specific electronic sensors for detecting clinically important biomolecules such as antibodies associated with human autoimmune diseases.
Bacterial biofilms and the encrustation of urethral catheters (1996)

Click to increase image sizeClick to decrease image sizeKey words: bacterial biofilmsurethral cathetersurinary tract infectioncatheter encrustation control