gebhart/patrepeval huggingface dataset:
Speech Intelligibility in Severe Adductor Spasmodic Dysphonia (2004)

This study compared speech intelligibility in nondisabled speakers and speakers with adductor spasmodic dysphonia (ADSD) before and after botulinum toxin (Botox) injection. Standard speech samples were obtained from 10 speakers diagnosed with severe ADSD prior to and 1 month following Botox injection, as well as from 10 age- and gender-matched healthy adults. This yielded 3 speaking conditions: pre-Botox injection, post-Botox injection, and normal control. Thirty phrases were extracted from the speech samples and arranged in a counterbalanced listening experiment. Thirty students, reporting little experience with distorted speech, served as listeners. Each listener's response was scored for words correctly identified using a liberal scoring criterion yielding a percentage of words correctly identified for each speaker. The results indicated that the speakers with ADSD were significantly more intelligible in the post-Botox condition than in the pre-Botox condition. The results also indicated that healthy speakers were significantly more intelligible than the speakers in both the pre- and post-Botox conditions. In general, these results indicated that intelligibility is affected in severe ADSD and that the use of Botox injection in ADSD improves intelligibility scores. However, the results also indicated that the use of Botox injection does not result in speech intelligibility similar to that of normal, non-ADSD speakers.
Optical Scanner for Immunoassays With Up-Converting Phosphorescent Labels (2008)

A 2-D optical scanner was developed for the imaging and quantification of up-converting phosphor (UCP) labels in immunoassays. With resolution better than 500 microm, a scan rate of 0.4 mm/s, and a 1-2% coefficient of variation for repeatability, this scanner achieved a detection limit of fewer than 100 UCP particles in an 8.8. x 10(4) microm(2) area and a dynamic range that covered more than three orders of magnitude. Utilizing this scanner, a microfluidic chip immunoassay for the cytokine interferon-gamma (IFN-gamma) was developed: concentrations as low as 3 pM (50 pg/mL) were detected from 100 microL samples with a total assay time of under an hour, including the 8 min readout. For this UCP-based assay, 2-D images of the capture antibody lines were scanned, image processing techniques were employed to extract the UCP emission signals, a response curve that spanned 3-600 pM IFN-gamma was generated, and a five-parameter logistic mathematical model was fitted to the data for determination of unknown IFN-gamma concentrations. Relative to common single-point or 1-D scanning optical measurements, our results suggest that a simple 2-D imaging system can speed assay development, reduce errors, and improve accuracy by characterizing the spatial distribution and uniformity of surface-captured optical labels as a function of assay conditions and device parameters.
Ligand Specific Efficiency (LSE) Index for PET Tracer Optimization (2016)

Ligand efficiency indices are widely used to guide chemical optimization in drug discovery, due to their predictive value in the early steps of optimization. At later stages, however, as more complex properties become critical for success, indices relying on calculated, rather than experimental, parameters become less informative. This problem is particularly acute when developing positron emission tomography (PET) imaging agents, for which nonspecific binding (NSB) to membranes and non-target proteins is a frequent cause of failure. NSB cannot be predicted using in silico parameters. To address this gap, we explored the use of the experimentally determined chromatographic hydrophobicity index on immobilized artificial membranes, CHI(IAM), to guide the optimization of NSB. The ligand specific efficiency (LSE) index was defined as the ratio between affinity (pIC50 or pKd ) and the logarithmic value of CHI(IAM). It allows for quantification of binding affinity to the target of interest, relative to NSB. Its use was illustrated by the optimization of PET tracer candidates for the prostacyclin receptor.
Synthesis of Thieno[2,3-d]pyrimidine Analogues of the Potent Antitumor Agent N-{4-[2-(2-Amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic Acid (LY231514) (1996)

Several thieno[2,3-dlpyrimidine analogues of the potent antitumor agent N-{4-[2-(2-amino-4(3~-oxo-7&pyrrolo[2,3-~pyrimidin-5-yl)e~yl]benzoylj-L-glutamic acid (LY231514,7) have been prepared by two different strategies.The fust involved S-alkylation of the 6-mercaptopyrimidines ( 13) and ( 14) with the a-haloketone (12), followed by cyclization to the thieno-
Antigen presentation and tumor cytotoxicity by interferon‐γ‐treated microglial cells (1987)

In this study microglial cells isolated from brain cell cultures of newborn mice were characterized and investigated for morphology, their responses to growth factors and their functional properties. The microglial cells were phagocytic, contained nonspecific esterase activity and expressed Fc (IgG1/2b) and type-3 complement receptors. Scanning electron microscopy revealed that in analogy to brain tissue two types of microglial cells are present in the cultures: the ameboid and the ramified type which both display similar appearance by transmission electron microscopy. Interleukin 3 and the granulocyte-macrophage colony-stimulating factor were potent growth factors for the cultured microglial cells. The cells were negative for class II antigens (Ia) of the major histocompatibility antigen complex. However, upon treatment with interferon-gamma (IFN-gamma) microglial cells became Ia+ and functioned as antigen-presenting cells when tested on ovalbumin-specific Ia-restricted helper T cells. Furthermore, microglial cells exposed to IFN-gamma and endotoxin developed tumor cell cytotoxicity and produced tumor necrosis factor alpha. Taken together, microglial cells share the characteristics of cells of the macrophage lineage.
17α-Hydroxylase/17,20 lyase inhibitor VN/124-1 inhibits growth of androgen-independent prostate cancer cells via induction of the endoplasmic reticulum stress response (2008)

Inhibitors of the enzyme 17alpha-hydroxylase/17,20 lyase are a new class of anti-prostate cancer agents currently undergoing preclinical and clinical development. We have previously reported the superior anticancer activity of our novel 17alpha-hydroxylase/17,20 lyase inhibitor, VN/124-1, against androgen-dependent cancer models. Here, we examined the effect of VN/124-1 on the growth of the androgen-independent cell lines PC-3 and DU-145 and found that the compound inhibits their growth in a dose-dependent manner in vitro (GI50, 7.82 micromol/L and 7.55 micromol/L, respectively). We explored the mechanism of action of VN/124-1 in PC-3 cells through microarray analysis and found that VN/124-1 up-regulated genes involved in stress response and protein metabolism, as well as down-regulated genes involved in cell cycle progression. Follow-up real-time PCR and Western blot analyses revealed that VN/124-1 induces the endoplasmic reticulum stress response resulting in down-regulation of cyclin D1 protein expression and cyclin E2 mRNA. Cell cycle analysis confirmed G1-G0 phase arrest. Measurements of intracellular calcium levels ([Ca2+]i) showed that 20 micromol/L VN/124-1 caused a release of Ca2+ from endoplasmic reticulum stores resulting in a sustained increase in [Ca2+]i. Finally, cotreatment of PC-3 cells with 5, 10, and 20 micromol/L VN/124-1 with 10 nmol/L thapsigargin revealed a synergistic relationship between the compounds in inhibiting PC-3 cell growth. Taken together, these findings show VN/124-1 is endowed with multiple anticancer properties that may contribute to its utility as a prostate cancer therapeutic.
Heat shock proteins and cell proliferation (1991)

Heat shock proteins (Hsps) carry out a number of essential functions in the cell. These functions could be utilized, in a developmentally regulated manner, to affect proteins necessary for cell growth and proliferation. Data showing Hsp involvement in cell proliferation under non-stress conditions are perhaps not altogether surprising in view of the important roles of Hsps in cell metabolism. In a number of cases stress can facilitate cell proliferation in cells which could otherwise not be amenable to this developmental pathway. It is proposed that Hsps could play an essential helper role in initiating this process.
Amplified Expression of Fructose 1,6-Bisphosphatase in Corynebacterium glutamicum Increases In Vivo Flux through the Pentose Phosphate Pathway and Lysine Production on Different Carbon Sources (2005)

The overexpression of fructose 1,6-bisphosphatase (FBPase) in Corynebacterium glutamicum leads to significant improvement of lysine production on different sugars. Amplified expression of FBPase via the promoter of the gene encoding elongation factor TU (EFTU) increased the lysine yield in the feedback-deregulated lysine-producing strain C. glutamicum lysCfbr by 40% on glucose and 30% on fructose or sucrose. Additionally formation of the by-products glycerol and dihydroxyacetone was significantly reduced in the PEFTUfbp mutant. As revealed by 13C metabolic flux analysis on glucose the overexpression of FBPase causes a redirection of carbon flux from glycolysis toward the pentose phosphate pathway (PPP) and thus leads to increased NADPH supply. Normalized to an uptake flux of glucose of 100%, the relative flux into the PPP was 56% for C. glutamicum lysCfbr PEFTUfbp and 46% for C. glutamicum lysCfbr. The flux for NADPH supply was 180% in the PEFTUfbp strain and only 146% in the parent strain. Amplification of FBPase increases the production of lysine via an increased supply of NADPH. Comparative studies with another mutant containing the sod promoter upstream of the fbp gene indicate that the expression level of FBPase relates to the extent of the metabolic effects. The overexpression of FBPase seems useful for starch- and molasses-based industrial lysine production with C. glutamicum. The redirection of flux toward the PPP should also be interesting for the production of other NADPH-demanding compounds as well as for products directly stemming from the PPP.
2.1 Å Crystal Structure of Human PXR in Complex with the St. John's Wort Compound Hyperforin, (2003)

The nuclear xenobiotic receptor PXR is activated by a wide variety of clinically used drugs and serves as a master regulator of drug metabolism and excretion gene expression in mammals. St. John's wort is used widely in Europe and the United States to treat depression. This unregulated herbal remedy leads to dangerous drug-drug interactions, however, in patients taking oral contraceptives, antivirals, or immunosuppressants. Such interactions are caused by the activation of the human PXR by hyperforin, the psychoactive agent in St. John's wort. In this study, we show that hyperforin induces the expression of numerous drug metabolism and excretion genes in primary human hepatocytes. We present the 2.1 A crystal structure of hyperforin in complex with the ligand binding domain of human PXR. Hyperforin induces conformational changes in PXR's ligand binding pocket relative to structures of human PXR elucidated previously and increases the size of the pocket by 250 A(3). We find that the mutation of individual aromatic residues within the ligand binding cavity changes PXR's response to particular ligands. Taken together, these results demonstrate that PXR employs structural flexibility to expand the chemical space it samples and that the mutation of specific residues within the ligand binding pocket of PXR tunes the receptor's response to ligands.
Selective Inhibition of Human Brain Tumor Cells through Multifunctional Quantum‐Dot‐Based siRNA Delivery (2009)

More than one job: Quantum dots (QDs) conjugated with thiol-modified small interfering RNA (siRNA) were functionalized with thiol-modified RGD and HIV-Tat peptides. These multifunctional QDs were used for the targeted delivery and tracking of siRNA molecules for the knockdown of the EGFRvIII gene, which led to the down-regulation of the PI3K-Akt signaling pathway and the apoptosis of malignant brain cancer cells.
Trauma-induced tumorigenesis of cells implanted into the rat spinal cord (2003)

Object. Findings in several clinical cases have suggested a correlation between tumor formation and previous injury to the central nervous system (CNS); however, the relationship between trauma and tumorigenesis has not been investigated well experimentally. In this study the authors provide evidence correlating tumorigenesis with trauma in the rat spinal cord. Methods. A glial cell line, C6R-G/H, which expresses green fluorescent protein (GFP) and hygromycin phosphotransferase (HPT), was implanted into normal and injured rat spinal cords. In all rats in which the cells were implanted into an injured site, locomotor function deteriorated and histological analysis demonstrated glioblastoma multiforme by 6 weeks; tumorigenesis was correlated with a loss of both GFP expression and resistance to hygromycin treatment. In contrast, no evidence of tumor formation was found at 6 weeks in rats in which the cells were implanted into healthy tissue. When C6R-G/H cells were treated with contused spinal cord extract in culture before implantation, they lost GFP expression and hygromycin resistance, and later formed tumors after implantation into normal spinal cord. Conclusions. The findings of this study indicate that trauma can induce tumorigenesis. Implantation of C6R-G/H cells into traumatized spinal cords resulted in their transformation, which was signaled by loss of GFP expression and hygromycin resistance accompanied by tumor formation. Exposure to extracts derived from injured spinal cord produced similar transformation and gene expression changes, as well as tumor formation after such cells were implanted into normal cords. Care, therefore, should be taken when cells are implanted into an injured CNS because of potential mutagenesis due to trauma-induced factors.
Lentiviral Vectors for the Delivery of DNA into Mammalian Cells (2004)

Vectors derived from oncoretroviruses, represented by the prototype Moloney murine leukemia virus (MMLV), are powerful tools for gene transfer into mammalian cells. Vectors derived from such viruses are able to carry an insert of up to 6.5 kb. Because Retroviridae and derived vectors insert their genome into the host chromosome, the transgene delivered by these viruses are stably expressed in the infected cells. From a safety standpoint, the vectors are designed to eliminate any need to carry viral genes or associated toxicities into the host cell. This also substantially reduces their potential immunogenicity. Finally, the titers achieved with these vectors can be very high, yielding efficient infection in a broad range of cell types.
A roll-to-roll process to flexible polymer solar cells: model studies, manufacture and operational stability studies (2009)

An inverted polymer solar cell geometry comprising a total of five layers was optimized using laboratory scale cells and the operational stability was studied under model atmospheres. The device geometry was substrate-ITO-ZnO-(active layer)-PEDOT:PSS-silver with P3HT-PCBM as the active layer. The inverted devices were compared to model devices with a normal geometry where the order of the layers was substrate-ITO-PEDOT:PSS-(active layer)-aluminium. In both cases illumination was through the substrate which requires that it is transparent. Both device types were optimized to a power conversion efficiency of 2.7% (1000 W m−2, AM1.5G, 72 ± 2 °C). The devices were operated under illumination while being subjected to different atmospheres to identify the dominant modes of degradation. Dry nitrogen (99.999%), dry oxygen (99.5%), humid nitrogen (90 ± 5% relative humidity) and ambient atmosphere (20% oxygen, 20 ± 5% relative humidity) were employed and both device types were found to be stable in a nitrogen atmosphere during the test period of 200 hours. The devices with a normal geometry where an aluminium electrode is employed gave stable operation in dry oxygen but did not give stable device operation in the presence of humidity. The inverted devices behaved oppositely where the less reactive silver electrode gave stable operation in the presence of humidity but poor stability in the presence of oxygen. The inverted model device was then used to develop a new process giving access to fully roll-to-roll (R2R) processed polymer solar cells entirely by solution processing starting from a polyethyleneterephthalate (PET) substrate with a layer of indium-tin-oxide (ITO). All processing was performed in air without vacuum coating steps and modules comprising eight serially connected cells gave power conversion efficiencies as high as 2.1% for the full module with 120 cm2 active area (AM1.5G, 393 W m−2) and up to 2.3% for modules with 4.8 cm2 active area (AM1.5G, 1000 W m−2).
Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma (2003)

Dihydrodiol dehydrogenase (DDH) is one of the major enzymes catabolizing polycyclic aromatic hydrocarbons in the liver. Although four DDH isoforms have been detected in the normal liver, only DDH1 and DDH2 have been detected in cancer cells of lung and esophagus. Moreover, the available information about hepatic pathophysiological regulation of DDH expression is limited. Therefore we addressed the question of DDH expression in patients with liver disorders, in particular, patients with hepatocellular carcinoma (HCC). Expression of DDH1/2 was determined by immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR) in 52 patients with resected HCC. DDH1/2 expression was detected in 31 (59.6%) of 52 pathological sections. Frequency of DDH1/2 expression was significantly higher in patients with tumor size >2 cm, and in those who had early local recurrence. In addition to the tumor size and frequency of local recurrence, our results further indicated that expression of DDH1/2 was correlated with those of cyclooxygenase 2 (COX-2), interleukin-6 (IL-6), microsomal epoxide hydrolase (mEpH) and soluble epoxide hydrolase (sEpH) in HCC patients. Interestingly, the expression of DDH1/2 was found inversely correlated with that of glutathione S-transferase (GST) and NADPH p450 reductase (NPR). In conclusion, these results indicate that DDH expression was significantly decreased in about 40% of HCC patients. However, in the bordering non-neoplastic region of liver DDH1/2 expression increased, and the increased DDH1/2 expression correlated with tumor size and the disease progression.
Direct alteration of a gene in the human genome (1986)

Direct alteration of a gene in the human genome requires an understanding of the role of the gene in metabolism. A gene may need to be introduced into a specific tissue or alternatively it may be possible to use accessible tissue such as bone marrow. The level of gene expression required also needs to be known as does the position in the genome into which the gene is to be inserted. Insertion of DNA needs to be of high efficiency and accuracy. Various methods are available including virus, the use of inert adjuvant, microinjection and electroporation. The procedure with the most potential for accuracy is the use of specially designed plasmids. The example of the use of such a plasmid in achieving target modification of the beta-globin gene is given. The method has high accuracy but low efficiency.
The Site of Action of Neurotensin in the Rat Pancreas (1991)

The tridecapeptide neurotensin, present in endocrine cells of the ileal mucosa and in nerve bodies of cerebral nuclei, may play a role in the physiology of exocrine pancreatic regulation. This assumption is based on two observations: Neurotensin appears in the blood stream after a fatty meal and neurotensin stimulates exocrine pancreatic secretion. There has, however, been controversy on the site of action of this peptide since some investigators did not observe an effect on the pancreas in vitro and suggested, therefore, an indirect, perhaps neural or even central site of action. In the present investigation, we compared the action of neurotensin on the exocrine pancreas in vivo in the anesthetized rat after intracerebroventricular (i.c.v.) injection and after i.v. infusion and in vitro after incubation of the pancreas in three different preparations: isolated dispersed acini, isolated lobuli, and isolated total pancreas. We found that i.c.v. application of neurotensin stimulated exocrine pancreatic secretion only when doses were applied that led to elevated peripheral plasma neurotensin levels. In vitro, the action of neurotensin was very weak and the optimal dose was integrity dependent; e.g., a concentration of 10(-4) and 10(-5) M neurotensin was necessary to stimulate amylase release from isolated acini, 10(-8) M neurotensin induced amylase release from isolates lobuli, and 10(-9) M neurotensin released amylase from the intact pancreas. Intravenously, neurotensin resulted in a greater amylase release over basal than in any of the in vitro experiments. We conclude that neurotensin acts directly on the pancreatic acini but that the sensitivity of the pancreas is greatly enhanced when the organ is intact and has normal neural and vascular communications.(ABSTRACT TRUNCATED AT 250 WORDS)
Silicone Resin Applications for Ceramic Precursors and Composites (2010)

This article reviews the applications of silicone resins as ceramic precursors. The historical background of silicone synthesis chemistry is introduced to explain the production costs and supply availability of various silicones. Thermal degradation processes of silicones are classified in terms of the main chain structure and cyclic oligomer expulsion process, which determine the resulting ceramic yield and the chemical composition. The high temperature decomposition of Si-O-C beyond 1,400 °C in an inert atmosphere and formation of a protective silica layer on material surfaces beyond 1,200 °C in an oxidative atmosphere are discussed from the viewpoints of the wide chemical composition of the Si-O-C materials. Applications of the resins for binding agents, as starting materials for porous ceramics, matrix sources with impregnation, fiber spinning and ceramic adhesions are introduced. The recent development of the process of filler or cross-linking agent additions to resin compounds is also introduced. Such resin compounds are useful for obtaining thick coatings, MEMS parts and bulk ceramics, which are difficult to obtain by pyrolysis of simple organometallic precursors without additives.
Lipoteichoic acid (LTA) from Staphylococcus aureus stimulates human neutrophil cytokine release by a CD14-dependent, Toll-like-receptor-independent mechanism: Autocrine role of tumor necrosis factor-α in mediating LTA-induced interleukin-8 generation (2006)

The LTA challenge provoked a dramatic release of cytokines, with an early appearance of TNF-alpha and IL-1beta and a delayed liberation of IL-8. The first phase of IL-8 production was induced directly by LTA, whereas the second phase was endogenously mediated by TNF-alpha, as it was largely abrogated by neutralizing anti-TNF-alpha antibodies. In contrast, IL1-beta was not involved in LTA-induced IL-8 generation. Interestingly, the late phase of IL-8 generation could also be attenuated by exogenous IL-10, probably as a consequence of its downregulatory effects on TNF-alpha generation. When investigating the mechanism of LTA-induced cellular activation, activity-neutralizing antibodies demonstrated that CD14 was involved in LTA-mediated neutrophil cytokine generation. Using antibodies that neutralize the activity of Toll-like receptor 2 (TLR2) or 4 (TLR4), we also show that CD14-dependent, LTA-induced neutrophil activation did not proceed via TLR2- or TLR4-mediated pathways. In conclusion, LTA is a potent activator of human neutrophil cytokine generation, with the synthesis of the chemokine IL-8 being largely dependent on TNF-alpha generation in an autocrine fashion. This LTA-induced effect was inhibited by IL-10, dependent on CD14, and independent of TLR 2 or 4.