gebhart/patrepeval huggingface dataset:
Communicating Change to Nonprofit Stakeholders (2001)

Relationships with organizational stakeholders are especially problematic for nonprofits in times of planned change. Implementers of change initiatives must negotiate demands for their time and attention as well as attend to severe resource constraints. Interviews with nonprofit administrators are used as the basis for the development of six models of implementation communication adopted by nonprofit implementers in interacting with various stakeholder groups. The data are also used as a basis for theorizing about two communicative dimensions of the task situation—communication efficiency and consensus building—which may be used to predict implementers’ choices of approach to their communication with stakeholders.
New Prodrugs of 9-(2-Phosphonomethoxyethyl)adenine [PMEA]: Synthesis and Stability Studies (1995)

Abstract The synthesis, and stability in different media of new PMEA prodrugs, with S-acylthioethyl (SATE) as enzyme-labile phosphonate protecting groups, are described in comparison with the already known Bis(POM)- and Bis(DTE)PMEA.
Solution-Liquid-Solid Growth of Crystalline III-V Semiconductors: An Analogy to Vapor-Liquid-Solid Growth (1995)

Until now, micrometer-scale or larger crystals of the III-V semiconductors have not been grown at low temperatures for lack of suitable crystallization mechanisms for highly covalent nonmolecular solids. A solution-liquid-solid mechanism for the growth of InP, InAs, and GaAs is described that uses simple, low-temperature (≤203°C), solution-phase reactions. The materials are produced as polycrystalline fibers or near-single-crystal whiskers having widths of 10 to 150 nanometers and lengths of up to several micrometers. This mechanism shows that processes analogous to vapor-liquid-solid growth can operate at low temperatures; similar synthesis routes for other covalent solids may be possible.
Development of dextran nanoparticles for stabilizing delicate proteins (2013)

One of the most challenging problems in the development of protein pharmaceuticals is to deal with stabilities of proteins due to its complicated structures. This study aims to develop a novel approach to stabilize and encapsulate proteins into dextran nanoparticles without contacting the interface between the aqueous phase and the organic phase. The bovine serum albumin, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), β-galactosidase, and myoglobin were selected as model proteins. The proteins were added into an aqueous solution containing the dextran and polyethylene glycol, and then encapsulated into dextran nanoparticles by aqueous-aqueous freezing-induced phase separation. The encapsulation efficiency and recovery of dextran nanoparticles were determined. The dextran nanoparticles loaded with proteins were characterized by scanning electron microscopy and particle size analysis. The protein aggregation was determined by size-exclusion chromatography-high-performance chromatography, and the bioactivity of proteins recovered during formulation steps was determined. The bioactivity of GM-CSF, G-CSF, and β-galactosidase were examined by the proliferation of TF-1 cell, NSF-60 cell, and ortho-nitrophenyl-β-galactoside assay, respectively. The results of bioactivity recovered show that this novel dextran nanoparticle can preserve the protein's bioactivity during the preparation process. LysoSensor™ Yellow/Blue dextran, a pH-sensitive indicator with fluorescence excited at two channels, was encapsulated into dextran nanoparticles to investigate the ability of dextran nanoparticles to resist the acidic microenvironment (pH < 2.5). The result shows that the dextran nanoparticles attenuate the acidic microenvironment in the poly (lactic-co-glycolic acid) microsphere by means of the dilution effect. These novel dextran nanoparticles provided an appealing approach to stabilize the delicate proteins for administration.
Dynamic Kinetic Resolution via Dual-Function Catalysis of Modified Cinchona Alkaloids:  Asymmetric Synthesis of α-Hydroxy Carboxylic Acids (2002)

A highly enantioselective catalytic transformation of racemic alpha-hydroxy acids to optically active alpha-hydroxy acids is reported. A new procedure was developed for the condensation of racemic alpha-hydroxy acids with trichloromethyl chloroformate (diphosgene) at room temperature in the presence of activated charcoal to form 5-substituted-1,3-dioxolane-2,4-diones in 90-100% yield. An efficient dynamic kinetic resolution of 5-aryl dioxolanediones was realized via a modified cinchona alkaloid-catalyzed alcoholytic opening of the dioxolanedione ring, generating a variety of optically active alpha-hydroxy esters in 91-96% ee and 61-85% chemical yield. In this dynamic kinetic resolution, the modified cinchona alkaloid was found to serve dual catalytic roles, mediating both the rapid racemization of the 5-aryl dioxolanediones and the enantioselective alcoholytic ring opening of the 5-aryl dioxolanediones. Consequently, both enantiomers of the 5-aryl dioxolanediones were converted to highly enantiomerically enriched aromatic alpha-hydroxy esters in yields (61-85%), far exceeding the maximum of 50% for a normal kinetic resolution. This development not only represents an expansion of the scope of asymmetric acyl-transfer catalysis of synthetic catalysts but also provides a new approach for the development of efficient chemical dynamic kinetic resolutions promoted by a single catalyst. 5-Alkyl dioxolanediones were resolved by a conventional but highly enantioselective kinetic resolution to provide alpha-hydroxy acids and esters in high optical purity and good yields.
Mechanism of specific nuclear transport of adriamycin: the mode of nuclear translocation of adriamycin-proteasome complex. (2001)

Adriamycin (ADM), an anthracycline anticancer agent, is selectively stored in the nuclei of a variety of proliferating cells, but the precise mechanism of specific nuclear transport of ADM is not well known. Recently, we demonstrated that ADM shows high binding affinity to the cytoplasmic proteasomes of L1210 mouse leukemia cells and that taken up ADM by the cells selectively binds to proteasomes. Nuclear targeting of proteasome in proliferating cells may be mediated by the nuclear localization signals that are found in several of the alpha-type subunits of the 20S proteasome. To confirm nuclear transport of the ADM-proteasome complex, we synthesized a photoactive ADM analogue, N-(p-azidohenzoyl)-ADM, and generated a photoaffinity-labeled proteasome complex. The 26S proteasome purified from the cytosol of L1210 cells had a high affinity to N-(p-azidobenzoyl)-ADM. SDS-PAGE analysis of the photoaffinity-labeled proteasome showed that low molecular weight bands (approximately 21-31 kDa) of 20S proteasome had the highest photoaffinity. The photoaffinity-labeled proteasome was distributed in the cytoplasm and nuclei of digitonin-permeabilized L1210 and B-16 mouse melanoma cells in the presence of the cytosolic fraction and ATP. The rate of nuclear translocation of the proteasome was low in the absence of ATP. These results suggest that the proteasome is a specific translocator of ADM from the cytoplasm to the nucleus and that 20S proteasome components are the dominant ADM-binding sites. The nuclear transport of ADM-proteasome complex is regulated by an ATP-dependent nuclear pore-mediated mechanism.
Nucleotide Sequence and Characterization of the Marek's Disease Virus Homologue of Glycoprotein B of Herpes Simplex Virus (1989)

The Marek's disease virus (MDV) homologue of the herpes simplex virus (HSV) gene encoding glycoprotein B (gB) has been identified within BamHI fragments I3 and K3 of the 'highly oncogenic' strain RB1B of MDV. The entire nucleotide sequence of the gene has been determined and its predicted amino acid sequence shown to share gross overall structural features with the gB genes of HSV, varicella-zoster virus (VZV) and other mammalian herpesviruses. In particular, all 10 cysteine residues were conserved in MDV gB and there was extensive homology throughout the gene with VZV, HSV and pseudorabies virus except for the N and C termini. The overall percentage amino acid identity between MDV gB and gB of the alphaherpesviruses had a mean of 50% which was almost twice that between cytomegalovirus and Epstein-Barr virus. Northern blot analysis showed that the main RNA transcribed from this gene is approx. 2.7 kb in size. Antibodies raised against synthetic peptides (residues 250 to 271 and 304 to 330) allowed the identification of a family of serologically related glycoproteins of Mr 110K, 64K and 48K in extracts of MDV-infected cells using immunoblots. Furthermore, the antisera were able to differentiate between the antigens of MDV and herpesvirus of turkeys in immunoblots. Immunofluorescence tests indicated that MDV gB is associated with granules in the cytoplasm and is present at the surface of MDV-infected cells.
Oral Activity of a Methylenecyclopropane Analog, Cyclopropavir, in Animal Models for Cytomegalovirus Infections (2004)

We reported previously that purine 2-(hydroxymethyl)methylenecyclopropane analogs have good activity against cytomegalovirus infection. A second-generation analog, (Z)-9-[[2,2-bis-(hydroxymethyl)cyclopropylidene]methyl]guanine (ZSM-I-62, cyclopropavir [CPV]), has particularly good activity against murine and human cytomegaloviruses (MCMV and HCMV) in vitro. To determine the oral activity of this compound in vivo, BALB/c or severe combined immunodeficient (SCID) mice infected with MCMV and two models using SCID mice implanted with human fetal tissue and subsequently infected with HCMV were used. In MCMV-infected normal mice, CPV at 10 mg/kg of body weight was highly effective in preventing mortality when administered at 24, 48, or 72 h post-viral inoculation and reduced titers of virus in tissues of SCID mice by 2 to 5 log10. In one HCMV model, human fetal retinal tissue was implanted into the anterior chamber of the mouse eye and inoculated with the Toledo strain of HCMV, and in the second, human fetal thymus and liver tissues were implanted under the kidney capsule of mice and then inoculated with HCMV. In general, replication of HCMV in both types of implant tissue increased from 7 through 21 to 28 days and then gradually decreased to undetectable levels by 8 weeks postinfection. Oral treatment with 45 or 15 mg of CPV/kg initiated 24 h after infection was highly effective in reducing replication to undetectable levels in both models and was generally more effective than ganciclovir. These data indicate that the methylenecyclopropane analog, CPV, was highly efficacious in these four animal models and should be evaluated for use in HCMV infections in humans.
Assessment of β-adrenergic receptor blockade after isamoltane, a 5-HT1-receptor active compound, in healthy volunteers (1993)

This study investigated the effects of isamoltane on the changes induced by cumulative doses of inhaled albuterol (salbutamol) on bronchomotor tone, skeletal muscle, circulatory system, and metabolism after single (day 1) and multiple dosing (day 7) in 15 healthy subjects. The volunteers were given placebo, 4 mg isamoltane, 10 mg isamoltane, or 20 mg propranolol over a 7-day period in a randomized, double-blind, crossover design. The greatest attenuation in albuterol-induced beta-adrenergic receptor responses occurred with propranolol. The median provocative dose of albuterol causing a 50% increase in specific airway conductance was 337 and 315 micrograms (day 1 and day 7, respectively) for placebo, 336 and 322 micrograms for 4 mg isamoltane, 344 and 389 micrograms for 10 mg isamoltane, and 667 and 652 micrograms for propranolol. The provocative dose of albuterol producing a 35% increase in tremor was 464 and 539 micrograms (day 1 and day 7, respectively) for placebo, 1122 and 1270 micrograms for 4 mg isamoltane, 1612 and > 1612 micrograms for 10 mg isamoltane, and > 1612 and > 1612 micrograms for propranolol. On day 5 of each period an exercise test was performed. Propranolol reduced exercise heart rate by 11% (compared with placebo), 10 mg isamoltane reduced heart rate by 5%, and 4 mg isamoltane reduced heart rate by 1%. In conclusion, low-dose isamoltane caused measurable systemic effects on both beta 2- and beta 1-adrenergic receptors, and the dose-dependent blockade on beta 2-receptors of skeletal muscle was more clear than the attenuation of exercise heart rate.
Potent siRNA Inhibitors of Ribonucleotide Reductase Subunit RRM2 Reduce Cell Proliferation In vitro and In vivo (2007)

An anti-RRM2 siRNA duplex is identified that exhibits significant antiproliferative activity in cancer cells of varying human type and species (mouse, rat, monkey); these findings suggest that this duplex is a promising candidate for therapeutic development.
Resonant optical modulators beyond conventional energy-efficiency and modulation frequency limitations (2010)

Modulator designs are proposed that can employ arbitrarily high-Q resonators to simultaneously achieve high energy efficiency and distortionless modulation at all (low/high) frequencies by completely decoupling optical cavity dynamics from the modulation frequency response.
Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism (2009)

Hydrogen sulfide (H(2)S) is one of three endogenous gases, along with carbon monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular actions in vivo. Although it has been demonstrated that CO or NO can trigger the development of a preconditioned phenotype in postischemic tissues, it is unclear whether H(2)S may also induce protection in organs subsequently exposed to ischemia-reperfusion (I/R). In light of these observations, we postulated that preconditioning with the exogenous H(2)S donor sodium hydrosulfide (NaHS-PC) would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h, before I/R causes postcapillary venules to shift to an anti-inflammatory phenotype in wild-type (WT) mice such that these vessels fail to support LR and LA during reperfusion. The protective effect of NaHS-PC on LR was largely abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT animals and was absent in endothelial NOS-deficient (eNOS(-/-)) mice. A similar pattern of response was noted in WT mice treated concomitantly with NaHS plus p38 mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002). Whereas the reduction in LA induced by antecedent NaHS was attenuated by pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect of NaHS was still evident in eNOS(-/-) mice. Thus NaHS-PC prevents LR and LA by triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However, the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than its effect to reduce LR.
In situ transformations of Pd/NHC complexes with N-heterocyclic carbene ligands of different nature into colloidal Pd nanoparticles (2018)

A series of Pd/NHC species undergoes R–NHC coupling reaction forming catalytically active NHC-free complexes and/or colloidal Pd nanoparticles.
Antennapedia and HIV Transactivator of Transcription (TAT) “Protein Transduction Domains” Promote Endocytosis of High Molecular Weight Cargo upon Binding to Cell Surface Glycosaminoglycans (2003)

Protein transduction domains (PTDs) are short basic peptide sequences present in many cellular and viral proteins that mediate translocation across cellular membranes. PTDs have become widely used as tools for the delivery of high Mr polypeptides, polynucleotides, or nanoparticles to cells in culture; and even the transfer of cargo molecules to the tissue of live animals has been reported. These cell-permeable peptides are functional when fused in-frame to recombinant polypeptides or when chemically coupled to their cargo. The mechanism responsible for PTD-mediated membrane translocation is controversially discussed and may vary among the various PTDs reported in the literature. Thus direct physical interaction with membrane lipids resulting in vectorial delivery to cells has been proposed for the Antennapedia (Antp) PTD, whereas uptake by the retroviral TAT (transactivator of transcription) protein PTD seems to require cell surface-expressed glycosaminoglycans. The view that PTD-mediated cellular uptake is energy-independent has been dismissed recently as an artifact resulting from fixation of cells. The data reported here agree with and further extend this work. They support the idea that certain PTDs promote cellular uptake via endocytosis and require the expression of negatively charged glycosaminoglycans on the surface of the target cells. Uptake of Antp PTD conjugates or peptide-derivatized liposomes was blocked by heparan sulfate proteoglycans, whereas TAT-mediated uptake was inhibited by both heparin and dextran sulfate. Mutant cells defective for glycosaminoglycan synthesis showed dramatically reduced Antp- or TAT-mediated transmembrane transport confirming the role of these complex polysaccharides in PTD-mediated cellular uptake. The fact that PTDs selectively interact with distinct glycosaminoglycan species has implications for therapeutic applications and may allow targeting of selective tissues that differ in their surface-expressed glycosaminoglycan patterns.
Example-based chat-oriented dialogue system with personalized long-term memory (2015)

This study introduces an example-based chat-oriented dialogue system with personalization framework using long-term memory. Previous representative chat-bots use simple keyword and pattern matching methodologies. To maintain the quality of systems, generating numerous heuristic rules with human labour is inevitable. The language expert knowledge is also necessary to build those rules and matching patterns. To avoid high annotation cost, example-based dialogue management is adopted for building chat-oriented dialogue system. We also propose three features: POS-tagged tokens for sentence matching, using NE types and values for searching proper responses, and using back-off responses for unmatched user utterances. Also, our system automatically collects user-related facts from user input sentences and stores the facts into a long-term memory. System responses can be modified by applying user-related facts in the long-term memory. A relevance score of a system response is proposed to select responses that include user-related fact, or frequently used responses. In several experiments, we have found that our proposed features contribute to improve the performance and our system shows competitive performance to ALICE system with the same training corpus.
p‐quinone mediates 6‐hydroxydopamine‐induced dopaminergic neuronal death and ferrous iron accelerates the conversion of p‐quinone into melanin extracellularly (2005)

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). 6-Hydroxydopamine (6-OHDA), a dopaminergic neurotoxin, is detected in human brains and the urine of PD patients. Using SH-SY5Y, a human neuroblastoma cell line, we demonstrated that 6-OHDA toxicity was determined by the amount of p-quinone produced in 6-OHDA auto-oxidation rather than by reactive oxygen species (ROS). Glutathione (GSH), which conjugated with p-quinone, provided significant protection whereas catalase, which detoxified hydrogen peroxide and superoxide anions, failed to block cell death caused by 6-OHDA. Although iron accumulated in the SN of patients with PD can cause dopaminergic neuronal degeneration by enhancing oxidative stress, we found that extracellular ferrous iron promoted the formation of melanin and reduced the amount of p-quinone. The addition of ferrous iron to the culture medium inhibited caspase-3 activation and apoptotic nuclear morphologic changes and blocked 6-OHDA-induced cytotoxicity in SH-SY5Y cells and primary cultured mesencephalic dopaminergic neurons. These data suggested that generation of p-quinone played a pivotal role in 6-OHDA-induced toxicity and extracellular iron in contrast to intracellular iron was protective rather than harmful because it accelerated the conversion of p-quinone into melanin.
Deep tissue targeted near-infrared optogenetic stimulation using fully implantable upconverting light bulbs (2015)

We demonstrate for the first time, the possibility of targeted optogenetic stimulation of neurons deep into brain tissue (>2 mm) in a minimally-invasive way by sending near-infrared light through tissue to excite passive lanthanide-doped blue-emitting upconverting nanocrystals (UCNPs) encapsulated in Parylene C microstructure light bulbs that emit visible (blue) light and locally excite opsins with high spatial resolution.
Comparison of the ability of lactate dehydrogenase-elevating virus and its virion RNA to infect murine leukemia virus-infected or -uninfected cell lines (1993)

Lactate dehydrogenase-elevating virus (LDV) has a strict species specificity. Cells or cell lines other than a particular subset of mouse primary macrophages which can support LDV replication in vitro have not been identified. LDV induces neurological disorders in old C58 or AKR strains, in which the involvement of multiple copies of the endogenous N-tropic murine leukemia virus (MuLV) genome and the Fv-1 locus of the mouse has been implicated. Our previous studies have demonstrated that LDV could infect and replicate in cell lines of the mouse or other species in vitro when they were infected with MuLV. The significance of and the precise mechanism underlying this phenomenon, however, remain unclear. We demonstrated in this study the efficient infection and replication of the virus in vitro by inoculation of its RNA mixed with liposome. No significant difference either in the efficiency of RNA transfection or in the ability to support its replication was observed among the various species' cell lines examined. In addition, by RNA transfection the virus replicated with equal efficiency in MuLV-infected and -uninfected cells or in macrophages derived from mice irrespective of their age. In contrast, the pattern of the infection by virus particles was quite different; LDV replication was observed only in macrophages (particularly from newborn mice) and MuLV-infected cells. By using various LDV isolates, it was demonstrated that the capability of replication between neurovirulent, LDV type C, and the other avirulent strains was almost the same in mouse cell lines when their RNA was introduced into the cells. Higher infectivity of LDV-C to MuLV-infected cells may be due to its efficient incorporation of the particles into MuLV-infected cells.
Cutting Edge: CpG DNA Inhibits Dendritic Cell Apoptosis by Up-Regulating Cellular Inhibitor of Apoptosis Proteins Through the Phosphatidylinositide-3′-OH Kinase Pathway (2002)

CpG DNA has been recognized as a powerful stimulant of dendritic cells (DCs). In this study, we demonstrate that CpG DNA inhibits spontaneous apoptosis of DCs. CpG DNA up-regulated cellular inhibitor of apoptosis proteins (cIAPs) as well as Bcl-2 and Bcl-x(L), but down-regulated active caspase-3. Although CpG DNA activated p38 mitogen-activated protein kinase, extracellular signal-related kinase, and phosphatidylinositide-3'-OH kinase (PI3K), only the blocking of PI3K inhibited the CpG DNA-induced DC survival. Moreover, while the expression of Bcl-2 and Bcl-x(L) depends on both PI3K and p38 mitogen-activated protein kinase, the up-regulation of cIAPs and the down-regulation of active caspase-3 by CpG DNA require PI3K activation, suggesting PI3K-dependent up-regulation of cIAPs in the antiapoptotic activity of CpG DNA in DCs. This study indicates that CpG DNA provides a survival signal to DCs, which might be one of mechanisms by which bacterial DNA stimulates and maintains the innate immune responses.