gebhart/patrepeval huggingface dataset:
Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA. Implications for the treatment of Parkinson's disease. (1995)

The hypothesis that L-DOPA therapy in Parkinson's disease may augment neuronal damage and thus accelerate the progression of the disease remains controversial. In this study, we demonstrate that L-DOPA induces death of catecholaminergic cells in vitro via an active program of apoptosis. Treatment of PC12 cells with clinically applicable concentrations of L-DOPA (25-100 microM) induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation, membrane blebbing, and internucleosomal DNA fragmentation. L-DOPA-induced apoptosis was cell and drug-type specific. Toxicity is an intrinsic property of the drug molecule since it was not suppressed by inhibiting conversion of L-DOPA to dopamine. However, L-DOPA toxicity was inhibited by antioxidants, suggesting that activation of apoptosis is mediated by oxygen radicals. Our finding that L-DOPA-induced cell death in vitro occurs via apoptosis explains the lack of evidence supporting its toxicity in vivo, since apoptotic neurons are rapidly phagocytosed in vivo without causing damage to surrounding tissue. Furthermore, since apoptosis is an active cellular program which can be modulated, we suggest clinical approaches for decreasing L-DOPA toxicity, thus preventing acceleration of neuronal damage in Parkinson's disease.
The B7-H1 (PD-L1) T Lymphocyte-Inhibitory Molecule Is Expressed in Breast Cancer Patients with Infiltrating Ductal Carcinoma: Correlation with Important High-Risk Prognostic Factors (2006)

B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.
Mechanisms of buffer therapy resistance (2014)

Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit.
Portable radiation spectrometer using low power digital pulse processing (2003)

A portable radiation spectrometer was developed based on real time digital signal processing. A single chip, low power digital pulse processor incorporates the trapezoidal pulse shaper, a fast discriminator, base-line restorer, peak detector, pile-up rejector and the data acquisition circuitry. The processor operates at 25 MHz clock speed and has active power consumption of less than 600 mW. The front-end electronics provide analog signal conditioning and data conversion with power consumption of less than 600 mW. The spectrometer is powered by a single battery, exploits a USB interface and fits in a small package with dimensions 15/spl times/18/spl times/3.8 cm.
3D Image Sensors, an Overview (2008)

We briefly introduce the current state in the most widely used 3D image sensors in computer vision today. Passive and active sensing methods are discussed, with highlight on difficult computer vision problems that can be avoided by using active methods. Active optoelectronic imaging methods like time of flight, interferometry and triangulation are presented. The 3D image processing applications included in this issue are reviewed and some conclusions drown.
Behavioral pharmacology of N-methyl-d-aspartate antagonists: Implications for the study and pharmacology of anxiety and schizophrenia. (1997)

N-Methyl-D-aspartate (NMDA) antagonists have behavioral effects in animals that may have implications for treatment or understanding of anxiety and schizophrenia. Whereas the anxiolytic effects of NMDA antagonists in animal screening procedures may have direct therapeutic applications for the pharmacotherapy of anxiety disorders, the effects of these drugs in startle and drug discrimination procedures have indirect implications for the study of schizophrenia. For example, investigation of the interaction and shared activity of NMDA antagonists and dopamine agonists may aid in understanding the interaction of dopamine and glutamate systems in schizophrenia. In addition, this type of study may result in development of screening procedures for atypical antipsychotics useful in the treatment of schizophrenia resistant to pharmacotherapy with traditional antipsychotics. Finally, examination of the discriminative stimulus effects of NMDA antagonists may allow prediction of adverse subjective effects of potential medications of this class.
Highly efficient, thermally and chemically stable nonlinear optical chromophores based on the α-perfluoroaryldicyanovinyl electron acceptors (1999)

A series of highly efficient, chemically and thermally stable (>310 °C) nonlinear optical chromophores were prepared through the replacement of the most reactive CN group in tricyanovinylthiophene derivatives with perfluoroaryl units.
A Convolutional Encoder Model for Neural Machine Translation (2017)

The prevalent approach to neural machine translation relies on bi-directional LSTMs to encode the source sentence. We present a faster and simpler architecture based on a succession of convolutional layers. This allows to encode the source sentence simultaneously compared to recurrent networks for which computation is constrained by temporal dependencies. On WMT'16 English-Romanian translation we achieve competitive accuracy to the state-of-the-art and on WMT'15 English-German we outperform several recently published results. Our models obtain almost the same accuracy as a very deep LSTM setup on WMT'14 English-French translation. We speed up CPU decoding by more than two times at the same or higher accuracy as a strong bidirectional LSTM. 1
Fabrication of periodic domain inversion in an x-cut LiTaO3 (1993)

We report on the fabrication of periodic domain inversion on the x face of LiTaO3 by selective proton exchange and quick heat treatment. Observation of domain formation in –c-cut LiTaO3 indicates an inside field model where electric field caused by proton diffusion reverses the orientation of domains. Based on this model, it has been found that an effective inside field to form domain inversion is also induced in x-cut LiTaO3 by using selective proton exchange. Accordingly, periodic domain inversion at 10 μm intervals has been successfully formed on the x face of LiTaO3.
Stable suppression of gene expression by RNAi in mammalian cells (2002)

In a diverse group of organisms including plants, Caenorhabditis elegans, Drosophila, and trypanosomes, double-stranded RNA (dsRNA) is a potent trigger of gene silencing. In several model systems, this natural response has been developed into a powerful tool for the investigation of gene function. Use of RNA interference (RNAi) as a genetic tool has recently been extended to mammalian cells, being inducible by treatment with small, approximately 22-nt RNAs that mimic those produced in the first step of the silencing process. Here, we show that some cultured murine cells specifically silence gene expression upon treatment with long dsRNAs (approximately 500 nt). This response shows hallmarks of conventional RNAi including silencing at the posttranscriptional level and the endogenous production of approximately 22-nt small RNAs. Furthermore, enforced expression of long, hairpin dsRNAs induced stable gene silencing. The ability to create stable "knock-down" cell lines expands the utility of RNAi in mammalian cells by enabling examination of phenotypes that develop over long time periods and lays the groundwork for by using RNAi in phenotype-based, forward genetic selections.
Identifying the amylome, proteins capable of forming amyloid-like fibrils (2010)

The amylome is the universe of proteins that are capable of forming amyloid-like fibrils. Here we investigate the factors that enable a protein to belong to the amylome. A major factor is the presence in the protein of a segment that can form a tightly complementary interface with an identical segment, which permits the formation of a steric zipper-two self-complementary beta sheets that form the spine of an amyloid fibril. Another factor is sufficient conformational freedom of the self-complementary segment to interact with other molecules. Using RNase A as a model system, we validate our fibrillogenic predictions by the 3D profile method based on the crystal structure of NNQQNY and demonstrate that a specific residue order is required for fiber formation. Our genome-wide analysis revealed that self-complementary segments are found in almost all proteins, yet not all proteins form amyloids. The implication is that chaperoning effects have evolved to constrain self-complementary segments from interaction with each other.
Microbial Cellulose Utilization: Fundamentals and Biotechnology (2002)

Fundamental features of microbial cellulose utilization are examined at successively higher levels of aggregation encompassing the structure and composition of cellulosic biomass, taxonomic diversity, cellulase enzyme systems, molecular biology of cellulase enzymes, physiology of cellulolytic microorganisms, ecological aspects of cellulase-degrading communities, and rate-limiting factors in nature. The methodological basis for studying microbial cellulose utilization is considered relative to quantification of cells and enzymes in the presence of solid substrates as well as apparatus and analysis for cellulose-grown continuous cultures. Quantitative description of cellulose hydrolysis is addressed with respect to adsorption of cellulase enzymes, rates of enzymatic hydrolysis, bioenergetics of microbial cellulose utilization, kinetics of microbial cellulose utilization, and contrasting features compared to soluble substrate kinetics. A biological perspective on processing cellulosic biomass is presented, including features of pretreated substrates and alternative process configurations. Organism development is considered for "consolidated bioprocessing" (CBP), in which the production of cellulolytic enzymes, hydrolysis of biomass, and fermentation of resulting sugars to desired products occur in one step. Two organism development strategies for CBP are examined: (i) improve product yield and tolerance in microorganisms able to utilize cellulose, or (ii) express a heterologous system for cellulose hydrolysis and utilization in microorganisms that exhibit high product yield and tolerance. A concluding discussion identifies unresolved issues pertaining to microbial cellulose utilization, suggests approaches by which such issues might be resolved, and contrasts a microbially oriented cellulose hydrolysis paradigm to the more conventional enzymatically oriented paradigm in both fundamental and applied contexts.
Effect of food coadministration on 5-aminosalicylic acid oral suspension bioavailability (1990)

Single doses of 1 gm 5-aminosalicylic acid (5-ASA) suspension was administered to 24 healthy volunteers during both fasting and fed conditions. For subjects in a fasting state, plasma 5-ASA and acetyl 5-ASA concentrations peaked rapidly 1 hour after dosing to 14.72 micrograms/ml and 11.4 micrograms/ml, respectively. The elimination half-life of 5-ASA was 51.9 minutes, whereas the acetyl 5-ASA half-life could not be determined. A mean of 78.3% of the dose was excreted in the urine, with 5-ASA accounting for 21.2% of the dose and acetyl 5-ASA accounting for the balance. Only 11.3% of the dose was eliminated in the feces, consisting mostly of acetyl 5-ASA. Food coadministration reduced 5-ASA and acetyl 5-ASA systemic relative bioavailability to 44% and 76%, respectively, compared with the fasting treatment. Urinary excretion of the salicylates was reduced to 46.8%, and fecal salicylate elimination increased almost 100%--to 24.2% of the total dose.
Tissue factor and its extracellular soluble domain: the relationship between intermolecular association with factor VIIa and enzymic activity of the complex (1992)

We find that the isolated, extracellular domain of tissue factor (TF1-218; sTF) exhibits only 4% of the activity of wild-type transmembrane TF (TF1-263) in an assay that measures the conversion of factor X to Xa by the TF:VIIa complex. Further, the activity of sTF is manifest only when vesicles consisting of phosphatidylserine and phosphatidylcholine (30/70 w/w) are present. To determine whether the decreased activity results from weakened affinity of sTF for VIIa, we studied their interaction using equilibrium ultracentrifugation, fluorescence anisotropy, and an activity titration. Ultracentrifugation of the sTF:VIIa complex established a stoichiometry of 1:1 and an upper limit of 1 nM for the equilibrium dissociation constant (Kd). This value is in agreement with titrations of dansyl-D-Phe-L-Phe-Arg chloromethyl ketone active site labeled VIIa (DF-VIIa) with sTF using dansyl fluorescence anisotropy as the observable. Pressure dissociation experiments were used to obtain quantitative values for the binding interaction. These experiments indicate that the Kd for the interaction of sTF with DF-VIIa is 0.59 nM (25 degrees C). This value may be compared to a Kd of 7.3 pM obtained by the same method for the interaction of DF-VIIa with TF1-263 reconstituted into phosphatidylcholine vesicles. The molar volume change of association was found to be 63 and 117 mL mol-1 for the interaction of DF-VIIa with sTF and TF1-263, respectively. These binding data show that the sTF:VIIa complex is quantitatively and qualitatively different from the complex formed by TF1-263 and VIIa.
Pharmacokinetics of rolipram in the rhesus and cynomolgus monkeys, the rat and the rabbit. Studies on species differences (1988)

1. The pharmacokinetics of rolipram were studied in rat, rabbit, rhesus monkey and cynomolgus monkey using 14C- or 3H-labelled rolipram and a radioimmunoassay for measurement of unchanged drug. 2. Rolipram was rapidly and completely absorbed after oral doses of up to 50 mg/kg. Bioavailability was 0.1% in rhesus monkey, 3.7% in cynomolgus monkey, 3.6% in rabbit, 35% in rat, and 75% in man. 3. Rolipram was able to pass the blood-brain barrier achieving concentrations in brain twice those in plasma. 4. Plasma levels of the unchanged drug declined with a similar half-life of 1-3 h in all species investigated. In the rat, there were indications for a different clearance of the two rolipram enantiomers. 5. Labelled rolipram was excreted rapidly and completely. The main route of elimination was via the urine.
Human T‐cell recognition of epstein‐barr virus‐induced replication antigen complexes (1991)

Cellular immune responses to Epstein-Barr Virus (EBV)-associated antigens play an important role in the control of EBV-immortalized B lymphocytes. The nature of the antigens that serve as targets for these responses remains largely unknown. The purpose of the experiments reported here was to determine if virus-replication-associated antigens might function as targets for T-cell immunity with the emphasis on EBV-induced early antigen (EA) complex. Activated T-cell populations directed against this group of antigens would theoretically be effective in controlling the production of new virus progeny. Our results demonstrate that polypeptides associated with the EA complex do, in fact, induce the proliferation of memory T-cells from EBV-infected individuals irrespective of their serological status to the EA complex. The major polypeptide associated with the diffuse component of EA (EA-D) was notably effective in inducing a strong proliferative T-cell response. Cell lines established from EBV-infected individuals following continuous exposure to either p17 or p50 components of the EA complex over a 10- to 12-week period were composed primarily of CD4-positive T-cells, although CD8-positive cells also persisted for up to 9 weeks in culture. The data suggest that components of the EA complex might function as important target antigens in the immunosurveillance of EBV-infected cells.
Potential Therapeutic Agents for COVID-19 Based on the Analysis of Protease and RNA Polymerase Docking (2020)

The outbreak of novel coronavirus (COVID-19) infections occurring in 2019 is in dire need of finding potential therapeutic agents. In this study, we used molecular docking strategies to repurpose HIV protease inhibitors and nucleotide analogues for COVID-19. The evaluation was made on docking scores calculated by AutoDock Vina and RosettaCommons. Preliminary results suggested that Indinavir and Remdesivir have the best docking scores and the comparison of the docking sites of these two drugs shows a near perfect dock in the overlap region of the protein pocket. However, the active sites inferred from the proteins of SARS coronavirus are not compatible with the docking site of COVID-19, which may give rise to concern in the efficacy of drugs.
Implantable helical coil microwave antenna for interstitial hyperthermia (1988)

An implantable helical coil microwave antenna has been developed for improved localization and control of interstitial hyperthermia for deep-seated tumours. A helical coil structure was employed as an extension of the inner conductor at the terminal portion of a miniature semi-rigid coaxial cable. The antennas were constructed with three different connection configurations of the helical coil to the feedline, and with several coil turn densities during the optimization of heating characteristics. In order to compare relative antenna heating performance, a set of quantitative parameters was introduced. Power deposition profiles of 2450 MHz helical coil antennas were studied in both phantom models and muscle tissue in vivo, and compared to those of commonly used dipole antennas. Optimal antenna performance was obtained with a 10-turn per 1 cm helical coil connected to the inner conductor at the tip and separated from the outer conductor by a 0.1 cm gap (HCS-10). These antennas produced a well-localized heating pattern with a sharp falloff of temperature in both directions axially from the coil element. For half-wavelength insertion depths, the effective heating length (50 per cent of maximum SAR) of HCS-10 antennas matched that of standard dipole antennas, but was shifted down towards the tip. For shorter and deeper antenna insertion depths the HCS-10 heating pattern remained similarly localized to the region surrounding the helical coil with minimal cold zone at the tip. In contrast, the dipole antenna heating pattern changed significantly depending on insertion depth, with an unavoidable 0.2-0.7 cm cold region at the antenna tip and elevated surface temperatures for short insertion depths.
Transcranial magnetic stimulation (1996)

Transcranial magnetic stimulation (TMS) was used to investigate the delays in visual processing time produced by changes in luminance. By administering a magnetic pulse over the occipital pole 80-140 ms after the onset of visual stimuli, we could suppress perception of a four-digit number within a 30 ms time window. Commensurate with previous studies of visual processing latencies, a drop in luminance from 3.52 logTd to 2.61 logTd delayed the peak of the suppression window by 8.9 ms, while a further drop from 2.61 logTD to 1.75 logTd delayed the peak by an additional 15.4 ms. This study validates the use of TMS as a psychophysical tool.
Wnt Signaling Stimulates Osteoblastogenesis of Mesenchymal Precursors by Suppressing CCAAT/Enhancer-binding Protein α and Peroxisome Proliferator-activated Receptor γ (2007)

Mesenchymal precursor cells have the potential to differentiate into several cell types, including adipocytes and osteoblasts. Activation of Wnt/beta-catenin signaling shifts mesenchymal cell fate toward osteoblastogenesis at the expense of adipogenesis; however, molecular mechanisms by which Wnt signaling alters mesenchymal cell fate have not been fully investigated. Our prior work indicates that multipotent precursors express adipogenic and osteoblastogenic transcription factors at physiological levels and that ectopic expression of Wnt10b in bipotential ST2 cells suppresses expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) and increases expression of Runx2, Dlx5, and osterix. Here, we demonstrate that transient activation of Wnt/beta-catenin signaling rapidly suppresses C/EBPalpha and PPARgamma, followed by activation of osteoblastogenic transcription factors. Enforced expression of C/EBPalpha or PPARgamma partially rescues lipid accumulation and decreases mineralization in ST2 cells expressing Wnt10b, suggesting that suppression of C/EBPalpha and PPARgamma is required for Wnt/beta-catenin to alter cell fate. Furthermore, knocking down expression of C/EBPalpha, PPARgamma, or both greatly reduces adipogenic potential and causes spontaneous osteoblastogenesis in ST2 cells and mouse embryonic fibroblasts, suggesting that Wnt signaling alters the fate of mesenchymal precursor cells primarily by suppressing C/EBPalpha and PPARgamma.
Evaluation of a new enzyme‐linked immunosorbent assay for detection of Chagas antibody in US blood donors (2006)

These studies indicate that the prototype ELISA has excellent sensitivity and specificity for detection of antibodies to T. cruzi in donors. Moreover, among donations from a geographically selected collection region of the United States, observed seroprevalence was 0.03 percent.