gebhart/patrepeval huggingface dataset:
Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmacokinetic/pharmacodynamic relationships in humans. (1995)

The disposition of paclitaxel in humans is nonlinear. Paclitaxel metabolism to 6 alpha-hydroxylpaclitaxel is likely an important detoxification pathway. Myelosuppression is related to the duration that plasma paclitaxel concentrations are > or = 0.05 mumol/L. Trials of new doses and schedules of paclitaxel should take into account its nonlinear disposition to rule out adverse clinical consequences, especially if the drug is administered by short infusion. Our pharmacokinetic model should prove to be a powerful tool in predicting paclitaxel disposition, regardless of dose and schedule, and should facilitate further pharmacodynamic investigations.
Interstitial photoradiation injury of normal brain (1992)

The effect on normal brain of continuous interstitial laser irradiation at 630 nm through an implanted cylindrical-shape, diffusion-tipped optical fiber was studied in the rat. Brain water content in the laser irradiation area (LIA) and Evans blue (EB) dye content in selected areas of the brain were measured for different laser power outputs from 0 to 250 mW after 5 minutes of photoradiation. The degree and nature of tissue damage was examined histologically and correlated with the laser power level. There is significant brain damage, blood brain barrier (BBB) disruption, and brain edema in LIA for laser power outputs in excess of 100 mW from the diffusion tip (p less than 0.001). Brain edema in the LIA is strongly correlated with BBB disruption indicated by the presence of EB. Histologically, the cortical surface was more susceptible than deeper white matter regions to interstitial laser irradiation. Possible indirect mechanisms of brain injury from interstitial laser irradiation are discussed.
A 22-bp Fragment of the Pea Lectin Promoter Containing Essential TGAC-Like Motifs Confers Seed-Specific Gene Expression (1993)

Sylvia de Pater, Khanh Pham, Nam-Hai Chua, Johan Memelink, Jan Kijne, A 22-bp Fragment of the Pea Lectin Promoter Containing Essential TGAC-Like Motifs Confers Seed-Specific Gene Expression, The Plant Cell, Vol. 5, No. 8 (Aug., 1993), pp. 877-886
Insulin-like growth factor-I receptor antagonism results in increased cytotoxicity of breast cancer cells to doxorubicin and taxol (2001)

Therapeutic strategies for patients with advanced-stage adenocarcinoma of the breast frequently include the use of cytotoxic chemotherapy. Insulin-like growth factor I (IGF-I) receptor, a key factor in cell-cycle regulation, is frequently overexpressed in high-grade breast cancers. IGF-I receptor overexpression in these tumors may provide a target for novel molecular therapy against this disease. Early passage samples of estrogen-responsive (ER+) MCF 7 and estrogen receptor-negative (ER-) MDA-231 cells were cultured in semi-confluent conditions. Dose-titrations were performed for doxorubicin and taxol with receptor modulation using IGF-I or a competitive receptor inhibitor, alphaIR3. The addition of 100 ng/ml IGF-I resulted in a >2-fold mitogenic response in both ER+ and ER- cells. Receptor activation prior to the treatment with cytotoxic chemotherapeutic agents altered the pattern of response with a 26.3% increase in IC50. Doxorubicin and taxol both produced dose-related toxicity with IC50 of 0.05 microg/ml and 0.00 microg/ml respectively. The addition of alphaIR3 resulted in increased cytotoxicity in IGF-I stimulated cells compared with the use of doxorubicin or taxol alone. These results suggest that IGF-I receptor modulation alters the response to cytotoxic chemotherapeutic agents in breast cancer cells.
The Perceptual Window: Head Motion as a new Input Stream (1999)

ABSTRACT We introduce a novel interaction technique using head motions to control the location of a window viewpoint within its document space. Head motion is acquired by a non-intrusive head-tracker using computer vision. The tracking technique used in the system, namely correlation matching, is described in order to exhibit its strengths and weaknesses in the context of tightly coupled interaction. The output of the tracker is used in both a rate control interaction and a position control interaction. The benefit is demonstrated by two user studies built around two common GUI tasks: navigating in a two-dimensional document space, and moving an object from one place to another in a document. Our system, The Perceptual Window, allows significant improvements in task completion time after a short learning period.
CNS-derived neural progenitor cells for gene transfer of nerve growth factor to the adult rat brain: complete rescue of axotomized cholinergic neurons after transplantation into the septum (1995)

A CNS-derived conditionally immortalized temperature-sensitive neural progenitor (CINP) cell line was used to generate NGF-secreting cells suitable for intracerebral transplantation. The cells were transduced by repeated retroviral infection, using a vector containing the mouse NGF cDNA under the control of the LTR promoter. Subcloning at the permissive temperature (33 degrees C) identified a highly NGF-secreting clone (NGF-CINP), which contained multiple copies of the transgene and released NGF at a rate of 2 ng/hr/10(5) cells in vitro, both at 33 and 37 degrees C, which was approximately 1 order of magnitude higher than what was possible to achieve in the heterogeneously infected cell cultures. After transplantation to the brain, the NGF-CINPs differentiated into cells with a predominant glia-like morphology and migrated for a distance of 1-1.5 mm from the implantation site into the surrounding host tissue, without any signs of overgrowth and tumor formation. Grafts of NGF-CINP cells implanted into the septum of adult rats with complete fimbria-fornix lesion blocked over 90% of the cholinergic cell loss in the medial septum and grafts placed in the intact striatum induced accumulation of low-affinity NGF receptor positive fibers around the implantation site. Expression of the NGF transgene in vivo was demonstrated by RT-PCR at 2 weeks after grafting. It is concluded that the immortalized neural progenitors have a number of advantageous properties that make them highly useful experimental tools for gene transfer to the adult CNS.
Photocross-Linkable Polymers (1984)

Abstract Several processes of photocross-linking of polymers are based on the photodimerization of unsaturated groups and on the photodissociation of light labile groups, such as azides. In the present paper we will consider three different methods of cross-linking: 1. Photoinitiation of free radical polymerization of unsaturated side groups attached to a polymer molecule in the presence of a suitable photoinitiator, such as benzoin alkyl ether. 2. Photoinitiation of cationic polymerization of oxirane side groups in the presence of photolabile amine salts, such as diazonium salts, giving rise to the formation of Lewis acid. 3. Electron donor/acceptor complexation of side groups which on photoexcitation exchange an hydrogen atom; this results in cross-linking by free radical combination.
Alternate Assembly of Ordered Multilayers of SiO2 and Other Nanoparticles and Polyions (1997)

Alternate layer-by-layer assembly of colloidal SiO2 particles with polycations has been investigated by quartz crystal microbalance (QCM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). QCM measurement confirmed the high regularity and reproducibility of the assembling process that depends on particle concentration, particle size, and ionic strength. The individual adsorption step was completed within 15 s. The thickness of adsorbed layers increased with increasing SiO2 concentrations at the three particle sizes used (45, 25, and 78 nm in diameter), unlike the case for other polyion assemblies. It also increased with increasing ionic strength of aqueous SiO2 dispersions. According to SEM observation, the assembled film possessed surprisingly flat surfaces at optimized ionic strengths. AFM observation revealed that SiO2 particles were not closely packed. The neutralization ratio of SiO2 and PDDA was estimated by turbidity measurement. Comparison of turbidity and QCM data indicated that the positive charge on PDDA was not completely neutralized by the negative charge on SiO2 particles in the course of alternate adsorption. This is apparently caused by a large difference in rigidity and charge density between SiO2 and PDDA. Since the charge density on PDDA is significantly larger than that on SiO2, all of the former charges cannot form short-distance ion pairs with surface charges of rigid SiO2 particles. The formation of long-distance charge pairs between SiO2 and PDDA, unlike the case for oppositely charged pairs of linear polyions, appears to be the origin of the remarkable dependence of film thickness and surface morphology on ionic strength and particle concentration. The other nanoparticles (CeO2 and TiO2) were similarly assembled with oppositely-charged linear polyions. Further modifications of the film structure were demonstrated by assembly between particles with different sizes and that between SiO2 and enzyme and by taking advantage of premixing components.
Conformation and ion binding properties of peptides related to calcium binding domain III of bovine brain calmodulin (1989)

The conformational and ion binding properties of the sequences 93-104, 96-104, and 93-98 of domain III of bovine brain calmodulin (CaM) have been studied by CD and Tb3+-mediated fluorescence. In aqueous solution the interaction of all fragments with Ca2+ and Mg2+ ions is very weak and without any effect on the peptide conformation, which remains always random. In trifluoroethanol the interaction is very strong and the different fragments exhibit very distinct binding properties. In particular, the dodecapeptide fragment 93-104, and its N-terminal hexapeptide 98-104, bind calcium and magnesium with a very high binding constant (Kb greater than 10(5) M-1), undergoing a substantial conformational change. The structural rearrangement is particularly evident in the hexapeptide fragment, which tend to form a beta-bend. The C-terminal nonapeptide fragment 96-104 interacts with calcium and magnesium more weakly, and the binding process causes a decrease of ordered structure. These results suggest that, even in the entire dodecapeptide sequence corresponding to the loop of domain III of CaM, the calcium binding site is shifted toward the N-terminal hexapeptide segment. This interpretation is consistent with the results of crystallographic studies of CaM, which show that the calcium ions are located toward the amino terminal portion of the loop.
Identification of Two GTP-Binding Proteins in the Chloroplast Protein Import Machinery (1994)

Two of four proteins that associated with translocation intermediates during protein import across the outer chloroplast envelope membrane were identified as guanosine triphosphate (GTP)-binding proteins. Both proteins are integral membrane proteins of the outer chloroplast membrane, and both are partially exposed on the chloroplast surface where they were accessible to thermolysin digestion. Engagement of the outer membrane's import machinery by an import substrate was inhibited by slowly hydrolyzable or non-hydrolyzable GTP analogs. Thus, these GTP-binding proteins may function in protein import into chloroplasts.
Precursor‐directed production of erythromycin analogs by Saccharopolyspora erythraea (2001)

Diketide N-acetylcysteamine (diketide NAC) thioester precursors were fed to 6-Deoxyerythronolide B synthase (DEBS) ketosynthase-1 inactivated (KS1 degree) Saccharopolyspora erythraea strains to produce 13-substituted erythromycin analogs. This direct feeding process potentially represents a simplified production process over the current analog production system. Titers of these analogs were observed to increase linearly with the diketide concentration up to a precursor-specific saturation level. However, the rate of product formation was lower and the rate of diketide consumption higher with S. erythraea than was previously observed with a recombinant strain of Streptomyces coelicolor. Several strategies were pursued to address the issue of these high diketide consumption rates: (1) elucidation of the locale of diketide degradation, (2) addition of beta-oxidation inhibitors to the cultures, and (3) addition of a sacrificial diketide enantiomer to occupy putative degradative enzymes. Additionally, repeated addition of diketide to an S. erythraea KS1 degrees culture indicated that the titer of these erythromycin analogs is also currently limited by a shorter production period than observed during erythromycin synthesis by the parent strain. These results indicate potential avenues for expanding the use of this precursor-directed system from the generation of limited quantities of erythromycin analogs to a large-scale production system for these compounds.
Involvement of lysine residues in the binding of hGH and bGH to somatotropic receptors (1985)

The biological activities of human (hGH) and bovine (bGH) growth hormone derivatives obtained by chemical modification of the lysine residues were studied by radioreceptor assays using rabbit liver homogenates for somatotropic activity (SA). Control treatment with BH4 had a very slight effect on the SA, whereas the methylation and ethylation drastically reduced the activity of both hormones. Guanidination of these hormones and even acetimidination at a lower rate are accompanied by a considerable loss of biological activity. These results show the involvement of lysine residues in the interaction of hGH and bGH with somatotropic receptors. The structure-function relationship of these molecules is discussed, suggesting that the lysine or arginine residues in positions 41, 64, 70 and 115 might be particularly implicated.
Inhibition of Angiogenesis In Vivo by Interleukin 12 (1995)

Recognition of the mechanisms of the antiangiogenic properties of IL 12 may be crucial in planning its clinical applications, including a possibility of coadministration with other inhibitors of neovascularization.
Characterization of photocrosslinked alginate hydrogels for nucleus pulposus cell encapsulation (2008)

Intervertebral disc (IVD) degeneration is a significant health concern in the USA. Tissue engineering strategies have the potential to provide a viable alternative to current treatments. Nevertheless, such approaches require a suitable biomaterial scaffold for IVD tissue regeneration. Calcium crosslinked alginate has traditionally been used for in vitro culture of nucleus pulposus (NP) cells of the IVD. However, such ionically crosslinked hydrogels lose structural integrity over time. Recently, various polymers have been modified with photopolymerizable functional groups to create covalently crosslinked hydrogels. This technology may be employed to maintain the structural and mechanical integrity of three-dimensional alginate hydrogels. In this study, photocrosslinkable alginate was synthesized and evaluated for material properties and the ability to maintain the viability of encapsulated NP cells. Photocrosslinked alginate at varying percent modifications and weight/volume percentages displayed equilibrium swelling ratios and Young's moduli of 30.52 +/- 1.782 to 43.50 +/- 1.345 and 0.5850 +/- 0.1701 to 8.824 +/- 0.6014 kPa, respectively. The viability of encapsulated NP cells was highest in hydrogels at lower percent modifications, and decreased with time in culture. Taken together, this study is the first to demonstrate that photocrosslinked alginate can be used for cellular encapsulation and synthesized with tunable material properties that may be tailored for specific applications.
EFFECT OF DEXAMETHASONE ON CULTURED HUMAN TENOCYTES AND ITS REVERSIBILITY BY PLATELET-DERIVED GROWTH FACTOR (2003)

Dexamethasone significantly decreased cell viability, suppressed cell proliferation, and reduced collagen synthesis in cultured human tenocytes. The effects were reversed by the simultaneous administration of PDGFBB.
Glutamine: a major energy source for cultured mammalian cells. (1984)

Cultured mammalian cells have two primary mechanisms for obtaining energy necessary for growth: carbohydrate metabolism to lactate and glutamine oxidation to CO2. In tissue culture medium containing both glucose and glutamine, the contribution of glutamine oxidation to the energy requirement ranges between 30 and 50%. As the glucose concentration is decreased, or when glucose is replaced by other carbohydrates, the rate of glutamine oxidation increases and glutamine becomes the sole energy source for cultured cells. The rate of glutamine oxidation is regulated by the presence of glucose. The apparent absolute requirement for glucose or other carbohydrates in tissue culture medium is related to its role in anabolic reactions rather than in energy production. Oxidation of glucose, fatty acids, or ketone bodies does not contribute significantly to the energy needs of cultured mammalian cells. The data also suggest that consideration should be given to glutamine as an important energy source in vivo.
Ligand-independent growth hormone receptor dimerization occurs in the endoplasmic reticulum and is required for ubiquitin system-dependent endocytosis (2002)

The regulatory effect of growth hormone (GH) on its target cells is mediated via the GH receptor (GHR). GH binding to the GHR results in the formation of a GH-(GHR)(2) complex and the initiation of signal transduction cascades via the activation of the tyrosine kinase JAK2. Subsequent endocytosis and transport to the lysosome of the ligand-receptor complex is regulated via the ubiquitin system and requires the presence of an intact ubiquitin-dependent endocytosis (UbE) motif in the cytosolic tail of the GHR. Recently, the model of ligand-induced receptor dimerization has been challenged. In this study, ligand-independent GHR dimerization is demonstrated in the endoplasmic reticulum and at the cell surface by coimmunoprecipitation of an epitope-tagged truncated GHR with wild-type GHR. In addition, evidence is provided that the extracellular domain of the GHR is not required to maintain this interaction. Internalization of a chimeric receptor, which fails to dimerize, is independent of an intact UbE-motif. Therefore, we postulate that dimerization of GHR molecules is required for ubiquitin system-dependent endocytosis.
Structure−Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3 (2009)

In cancer cells, signal transducer and activator of transcription 3 (Stat3) participates in aberrant growth, survival, angiogenesis, and invasion signals and is a validated target for anticancer drug design. We are targeting its SH2 domain to prevent docking to cytokine and growth factor receptors and subsequent signaling. One of the important elements of the recognition sequence, pTyr-Xxx-Xxx-Gln, is glutamine. We incorporated novel Gln mimics into a lead peptide, pCinn-Leu-Pro-Gln-NHBn, and found that a linear, unconstrained side chain and carboxamide are necessary for high affinity, and the benzamide can be eliminated. Replacement of Gln-NHBn with (R)-4-aminopentanamide or 2-aminoethylurea produced inhibitors with equal or greater potency than that of the lead, as judged by fluorescence polarization (IC(50) values were 110 and 130 nM, respectively). When Pro was replaced with cis-3,4-methanoproline, the glutamine mimic, (4R,5S)-4-amino-5-benzyloxyhexanamide resulted in an IC(50) of 69 nM, the highest affinity Stat3 inhibitor reported to date.
Crystalline Solids of Alloy Clusters (2000)

AuAg alloy clusters protected with octadecanethiol (ODT) monolayers form crystalline solids whose powder X-ray diffractograms can be indexed to single cubic unit cells. These solids can also be regarded as superlattices of alloy clusters. The bulk Au:Ag ratio is significantly different from the metal salt feed ratio used for the synthesis of the alloy clusters. The surface plasmon resonance band of the alloy clusters shift monotonically with change in composition and only one distinct band is seen in the composition range, indicating that the single metal core containing alloy clusters are not forming. The shifts observed can be linearly related to the compositions. Atomic emission spectroscopy gives similar compositions as determined from absorption spectroscopy. The monolayer coverage determined from thermogravimetry increases with an increase in silver concentration. Thermal stability of the monolayers is comparable to pure Au and Ag clusters and no change in desorption temperature is observed with composition. Both monolayer melting and superstructure melting transitions are seen in the differential scanning calorimetry of the solids. Infrared spectroscopy suggests that the monolayers are essentially solidlike and the conformations are similar to the monolayers on pure Ag clusters. Some of the bands exhibit factor group splitting in the Au-rich composition, which is observed in other compositions upon annealing.
How the nature of the chemical bond governs resistance to amorphization by radiation damage (2005)

We discuss what defines a material's resistance to amorphization by radiation damage. We propose that resistance is generally governed by the competition between the short-range covalent and long-range ionic forces, and we quantify this picture using quantum-mechanical calculations. We calculate the Voronoi deformation density charges and Mulliken overlap populations of 36 materials, representative of different families, including complex oxides. We find that the computed numbers generally follow the trends of experimental resistance in several distinct families of materials: the increase (decrease) of the short-range covalent component in material's total force field decreases (increases) its resistance.
Highly Efficient Synthesis of O-(2,4-Dinitrophenyl)hydroxylamine. Application to the Synthesis of Substituted N-Benzoyliminopyridinium Ylides (2003)

An efficient two-step synthesis of O-(2,4-dinitrophenyl)hydroxylamine is described along with a comparison of its aminating efficiency with O-mesitylenesulfonylhydroxylamine (MSH). It was used in an expedient N-amination/benzoylation procedure involving various substituted pyridines, leading to polysubstituted N-benzoyliminopyridinium ylides, and the scope of its amination power was studied.
High doses of biotin in chronic progressive multiple sclerosis: A pilot study (2015)

These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.