gebhart/patrepeval huggingface dataset:
Microvasculature Can Be Selectively Damaged Using Dye Lasers: A Basic Theory and Experimental Evidence in Human Skin (1981)

Basic theoretical considerations of the optical and thermal transfer processes that govern the thermal damage induced in tissue by lasers are discussed. An approximate, predictive model and data are proposed for the purpose of selecting a laser that maximizes damage to cutaneous blood vessels and minimizes damage to the surrounding connective tissue and the overlying epidermis. The variables of wavelength, exposure duration, and incident energy density are modeled, and a flashlamp-pumped dye laser operating at or near the 577 nm absorption band of HbO2, with a pulse width (0.3 microsecond) less than the estimated, approximately 1 millisecond, thermal relaxation times for microvessels is chosen for experimental exposures of normal Caucasian skin. Highly specific laser-induced damage to blood vessels is demonstrated both clinically and histologically. This is in striking contrast to the previously reported widespread, diffuse necrosis caused by other lasers. The incident energy and preliminary observations of wavelength and temperature dependence for vascular damage thresholds are consistent with theoretical predictions. Whereas typically 20 joules/cm2 of argon laser irradiation (514 and 488 nm, approximately 100 msec) is required to induce widespread thermal damage, the pulsed dye laser requires only about 2 joules/cm2 to induce highly specific vascular damage. The potential usefulness of dye laser-induced selective vascular damage as a treatment modality for portwine stain hemangiomas and other vascular lesions is discussed. In addition to possible treatment applications, the dye laser or other sources meeting the requirements for producing such damage may also offer a useful experimental tool for inducing predictable damage to microvasculature. Histopathologic and clinical studies related to these possibilities are in progress.
Assembly of a Chromosomal Replication Machine: Two DNA Polymerases, a Clamp Loader, and Sliding Clamps in One Holoenzyme Particle. (1995)

The nine-subunit DNA polymerase (Pol) III* coupled to its beta sliding clamp is a rapid and highly processive replicating machine. The multiple subunits are needed for the complicated task of duplicating the Escherichia coli chromosome. In this report, Pol III* was constituted from individual pure proteins, and its structure was studied. Constitution of the Pol III* particle requires an ordered addition of the subunits, and the final structure contains 14 polypeptides in the ratio alpha 2 epsilon 2 theta 2 tau 2 gamma 2 delta 1 delta' 1 chi 1 psi 1. The structure can be summarized as being composed of two core polymerases (alpha epsilon theta) held together by a dimer of tau and one gamma complex clamp loader (gamma 2 delta 1 delta' 1 chi 1 psi 1) for loading beta onto DNA. At the center of the structure, the related tau and gamma subunits form a heterotetramer upon which the two core polymerases and clamp loader proteins assemble. The single copy nature of the delta, delta', chi, and psi subunits confers a structural asymmetry with respect to the two polymerases, presumably for the different functions of replicating the leading and lagging strands.
YTHDC1 mediates nuclear export of N6-methyladenosine methylated mRNAs (2017)

<i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most abundant internal modification of eukaryotic messenger RNA (mRNA) and plays critical roles in RNA biology. The function of this modification is mediated by m<sup>6</sup>A-selective 'reader' proteins of the YTH family, which incorporate m<sup>6</sup>A-modified mRNAs into pathways of RNA metabolism. Here, we show that the m<sup>6</sup>A-binding protein YTHDC1 mediates export of methylated mRNA from the nucleus to the cytoplasm in HeLa cells. Knockdown of YTHDC1 results in an extended residence time for nuclear m<sup>6</sup>A-containing mRNA, with an accumulation of transcripts in the nucleus and accompanying depletion within the cytoplasm. YTHDC1 interacts with the splicing factor and nuclear export adaptor protein SRSF3, and facilitates RNA binding to both SRSF3 and NXF1. This role for YTHDC1 expands the potential utility of chemical modification of mRNA, and supports an emerging paradigm of m<sup>6</sup>A as a distinct biochemical entity for selective processing and metabolism of mammalian mRNAs.
Maternal Phenylketonuria and Hyperphenylalaninemia (1980)

Since many women with phenylketonuria (PKU) will have children of their own, we were interested in ascertaining the effect of maternal PKU and hyperphenylalaninemia on the offspring of such women. We reviewed the literature on this subject and obtained additional unpublished data through an international survey. Data were collected on 524 pregnancies in 155 women; in 34 pregnancies a low-phenylalanine diet was begun after or shortly before pregnancy was established. Among untreated pregnancies, the frequencies of mental retardation, microcephaly, and congenital heart disease were greatly increased over those in the normal population, and these increases correlated with the mother's blood levels of phenylalanine. Ninety-five per cent of mothers with blood phenylalanine concentrations of 20 mg per deciliter or higher had at least one mentally retarded child. Bias introduced by case-finding methods cannot explain these results. It is not clear from our review whether dietary treatment begun after conception is helpful, but treatment begun before conception should be evaluated.
<title>Microfabricated plastic chips by hot embossing methods and their applications for DNA separation and detection</title> (2000)

Design and fabrication of microfluidic devices on polymethylmethacrylate (PMMA) substrates using novel microfabrication methods are described. The image of microfluidic devices is transferred from quartz master templates possessing inverse image of the devices to plastic plates by using hot embossing method. The micro channels on master templates are formed by the combination of metal etch mask and wet chemical etching. The micromachined quartz templates can be used repeatedly to fabricate cheap and disposable plastic devices. The reproducibility of the hot embossing method is evaluated after using 10 channels on different plastics. The relative standard deviation of the plastic channel profile from ones on quartz templates is less than 1%. In this study, the PMMA chips have been demonstrated as a micro capillary electrophoresis ((mu) -CE) device for DNA separation and detection. The capability of the fabricated chip for electrophoretic injection and separation is characterized via the analysis of DNA fragments (phi) X174. Results indicate that all of the 11 DNA fragments of the size marker could be identified in less than 3 minutes with relative standard deviations less than 0.4% and 8% for migration time and peak area, respectively. Moreover, with the use of near IR dye, fluorescence signals of the higher molecular weight fragments ($GTR 603 bp in length) could be detected at total DNA concentrations as low as 0.1 (mu) g/mL. In addition to DNA fragments (phi) X174, DNA sizing of hepatitis C viral (HCV) amplicon is also achieved using microchip electrophoresis fabricated on PMMA substrate.
Induction of Neutralizing Antibodies and Th1-Polarized and CD4-Independent CD8+T-Cell Responses following Delivery of Human Immunodeficiency Virus Type 1 Tat Protein by Recombinant Adenylate Cyclase ofBordetella pertussis (2005)

ABSTRACT HIV-Tat, a conserved protein playing a key role in the early life cycle of the human immunodeficiency virus (HIV) has been proposed as a potential AIDS vaccine. An HIV-Tat-based vaccine should elicit a broad, long-lasting, and neutralizing immune response. We have previously demonstrated that the adenylate cyclase (CyaA) from Bordetella pertussis targets dendritic cells and delivers CD8 + and CD4 + T-cell epitopes into the major histocompatibility complex class I and class II presentation pathways. We have also showed that CyaA induced specific and protective cytotoxic T cell responses in vivo. Here, we designed a prototype vaccine based on the HIV type 1 Tat delivered by CyaA (CyaA-E5-Tat) and tested its capacity to induce HIV-Tat-specific cellular as well as antibody responses. We showed that immunization of mice by CyaA-E5-Tat in the absence of adjuvant elicited strong and long-lasting neutralizing anti-Tat antibody responses more efficient than those obtained after immunization with Tat toxoid in aluminum hydroxide adjuvant. Analyses of the anti-Tat immunoglobulin G isotypes and the cytokine pattern showed that CyaA-E5-Tat induced a Th1-polarized immune response in contrast to the Th2-polarized immune responses obtained with the Tat toxoid. In addition, our data demonstrated that HIV-Tat-specific gamma interferon-producing CD8 + T cells were generated after vaccination with CyaA-E5-Tat in a CD4 + T-cell-independent manner. Based on these findings, CyaA-E5-Tat represents an attractive vaccine candidate for both preventive and therapeutic vaccination involving CyaA as an efficient nonreplicative vector for protein delivery.
Growth Regulation of Cultured Human Pituitary Cells by Steroidal and Nonsteroidal Compounds in Defined Medium (1979)

Human pituitary tumor tissue has been used to derive a cell line from which a subline (18–54SF) has been continuously propagated for over 50 passages in serum-free medium without supplements. These cells grow with a generation time of 30–40 h in serum-free medium and excrete two functional products, a growth factor and PRL, into the conditioned medium. We have also found that the growth of 18–54SF cells may be inhibited by specific additions of steroidal and nonsteroidal compounds. The steroids progesterone, 17β-estradiol, and estrone inhibit 18–54,SF cell growth approximately 75% at concentrations of 3.2 × 10-6, 1.8 × 10-6, and 3 × 10-6M, respectively. Other progestin metabolites do not have any effect on growth at concentrations up to 1.7 × 10-5M. The nonsteroidal progestin analogs 17α-hydroxy-6α-methyl-A4-pregnen-3,20-dione, norethynodrel (17α-ethynyl-17beta;-hydroxy-5(10)-estren-3-one) and norethindrone (17-hydroxy-19-nor-17α-pregn-4-en-20yn-3-one) inhibited cell growth as well as or better than progesterone. Norethindrone was the most effective nonsteroidal progestin tested, inhibiting cell growth about 90% at addition of concentrations of 1.6 × 10-6M to serum-free medium. The nonsteroidal estrogen diethylstilbestrol inhibited 18–54,SF cell growth about 75% after 10 days of incubation at 1.85 × 10-7M in serum-free medium. Another nonsteroidal estrogen, ethynyl estradiol, was much less effective than diethylstilbestrol. None of the androgens tested affected the growth of these cells. The antiestrogens clomiphene citrate and MER-25 were also investigated. Clomiphene citrate and ethamoxytriphetol (MER-25) inhibited 18-54,SF cell growth about 50% at concentrations of 2-3 × 10-8 and 2–3 × 10-8M, respectively. At concentrations of 2 × 10-7 and 10-6 M or higher, clomiphene citrate and MER-25, respectively, caused extensive cell detachment from the dishes within 3–4 days and eventual cell death. The 18–54SF cultured human pituitary cell system should prove to be useful for analyzing specific factors that may affect the growth of human pituitary tumors.
The electronic states of polyfluorene copolymers with alternating donor-acceptor units (2004)

We calculate the electronic states of the low bandgap polyfluorene-based copolymer DiO-PFDTBT, which consists of alternating 9,9-dioctyl-9H-fluorene and 4,7-di-thiophen-2-ylbenzo[1,2,5]thiadiazole (TBT) units, and compare with the steady-state absorption, emission, and excitation spectrum. Using the semiempirical quantum-chemical (ZINDO) method we can assign the characteristic bands of the "camel-back" absorption spectrum to one charge transfer state at lower energy localized on the TBT unit, and one delocalized excitonic state at higher energy corresponding to the pi-conjugated electron system. Additional "dark" charge transfer states in the gap between these bands have been revealed. Calculations are also made on the red light emitting polyfluorene-based copolymer poly(fluorene-co-benzothiadiazole) (F8BT), which contains benzo[1,2,5]thiadiazole instead of TBT. The nature of the electronic states in F8BT and DiO-PFDTBT are found to be qualitatively the same.
Treatment of Parkinson’s disease in the advanced stage (2013)

Levodopa/Carbidopa, respectively, Levodopa/Benserazide is the most effective treatment for Parkinson's disease and during the progress of the disease, patients will inevitably need to be treated with it. Nonetheless, after a certain time period most of the patients experience side effects. Mainly disturbing are motor and non-motor fluctuations and dyskinesia. Numerous options from changing the medication regimen, to continuos dopaminergic drug delivery via apomorphine or Duodopa pumps and stereotactical interventions are available. The physician's responsibility is to choose the right therapeutic procedure for each timepoint of the patient's disease. In this review, we provide an up to date overview of the available strategies.
Inhibition of TGF- Signaling for the Treatment of Tumor Metastasis and Fibrotic Diseases (2011)

Transforming growth factor-β (TGF-β) is a cytokine involved in cell proliferation, apoptosis, differentiation, angiogenesis, cell adhesion, migration, extracellular matrix deposition, wound healing and immune regulation. The cellular response to TGF-β depends on the cell type and cell microenvironment. TGF-β supresses tumor growth in the early phase of neoplasia, while promotes tumor progression and metastasis in later phases. Thus, many malignant cells produce large amounts of TGF-β, but are resistant to its growth inhibitory effects. TGF-β produced by tumors depresses antitumor immune responses and diminishes cancer immunotherapy. TGF-β initiates the epithelial-to-mesenchymal transition (EMT) associated specifically with tumor invasiveness and metastasis and also with the generation of fibroblasts associated with accumulation of extracellular matrix in chronic fibrotic disorders. There are several possibilities for the disruption of TGF-β signaling: 1) targeting the expression and function of TGF-β by a small interfering RNA strategy, by a neutralizing TGF-β monoclonal antibody or by decreasing the enzymatic activity of furin, a TGF-β activating protease, 2) inhibiting TGF-β receptor kinase 1, named also activin receptor-like kinase (ALK5), activity by pyridinylimidazoles (SB- 431542, SB-505124, SB-525334, A-83-01), by 2,4-disubstituted pteridine (SD-208) or by a quinazoline-derived inhibitor (SD-093) which all interact with the ATP-binding site of ALK5; 3) inhibiting of Smad 2 and Smad 3 signaling by overexpression of their physiological inhibitor (Smad 7) or by using thioredoxin as an Smad anchor disambling Smad from activation; 4) inducing an immune response by administration of TGF-β-resistant cytotoxic T-lymphocytes or by the treatment with a small-molecule ALK5 inhibitor. Keywords: Inhibitory Smad, receptor-regulated Smads, small interfering RNA, TGF-β monoclonal antibody, TGF-β receptor kinase 1 inhibitors, TGF-β signaling, transforming growth factor-β, epithelial, –, to-mesenchymal transition (EMT), Smad1, Smad2, Smad3, Smad5, Smad4, C.elegans, Drosophila melanogaster, Xenopus, bone morphogenetic protein (BMP), Smad8, TRI, ALK5, ALK1, phosphatidylinositol-3 kinase/ Akt /protein kinase B, chromosome 10, Hedgehog, Notch, polyethylenimine, Cy-clodextrin nanoparticles, adeno-associated virus (AAV), lentiviral vectors, SNALPs, TGFDE, TGFSCR, scleroderma, trabeculectomy, GC-1008 (Fresolimumab), MDA-MB-231 tumors, MCF7 breast cancer, P144, P17, doxorubicin, urokinase-type plasminogen activator receptor, A549 alveolar epithelial and T98G glioblas-toma cell lines, furin-like protease (FLP), Decorin, Fetuin, hepatic stellate cells, PDGF, SalI restriction, 3 NotI restriction site, pEAG347, SV40, pSV2, pAA002, Chinese hamster ovary cells, A-Sepharose, TRII:Fc, FKHRL1 Forkhead, p38, SB-431542, ALK4-, ALK2, ALK3, ALK6-, NMuMG, Mv1Lu, EMT, Halofuginone, Tempostatin, RU 19110, simvastatin
Evolution of indocyanine green dye choroidal angiography (1995)

During the past three years, indocyanine green (ICG) fluorescence angiography has enjoyed an increasing popularity, especially among clinicians who treat age-related macular degeneration. Although the basic methodology for performing ICG angiography was developed and demonstrated in the early 1970s, nearly 20 years passed before the technology became commercialized for widespread clinical use. The developmental evolution of ICG choroidal angiography and its future clinical uses are discussed.
The importance of the anode field in controlling the generation rate of the donor states at the Si–SiO2 interface (1984)

The generation of positive charge at the Si–SiO2 interface during constant current electron injection has been investigated at low (Avalanche) and high (Fowler–Nordheim) fields at 295 and 77 K on several differently processed metal-oxide–semiconductor capacitors. It was found that the rate at which the charge is generated increases exponentially with the field at the anode for both polarities and independently of processing variables. It follows that water-related and other electron traps have the sole effect of enhancing the generation rate by increasing this field. The role of hot-electron energy losses at the SiO2-anode interface is also discussed.
Monocytes Are Major Players in the Prognosis and Risk of Infection After Acute Stroke (2009)

In human stroke, poor outcome is associated to innate responses mediated by Toll-like receptor-4 in monocytes. SAI may result from the immunosuppressive and antiinflammatory effects of corticoids, catecholamines, IL-10, and deactivated monocytes. Early treated SAI does not contribute significantly to additional brain damage. These findings encourage the exploration of strategies aimed to inhibit Toll-like receptor-4 signaling in acute stroke.
Decreased Hepatic Insulin-Like Growth Factor (IGF)-I and Increased IGF Binding Protein-1 and -2 Gene Expression in Experimental Uremia (1997)

The imbalance between normal insulin-like growth factor-I (IGF-I) and markedly increased IGF binding protein (IGFBP) plasma levels plays a pathogenic role for growth retardation and catabolism in children with chronic renal failure. To investigate the mechanism of these alterations, experiments were performed in an experimental model of uremia in rats (5/6 nephrectomy) and in pair-fed and ad libitum-fed sham-operated controls Using a specific solution hybridization/RNase protection assay, we observed a marked reduction of hepatic IGF-I messenger RNA (mRNA) abundance at steady state in uremic animals (37 +/- 5% of control) compared both with pair-fed (65 +/- 10%) and ad libitum-fed controls (100 +/- 11%) (P < 0.001). Reduced IGF-I gene expression was clearly organ-specific; it was most pronounced in liver (significant vs., pair-fed controls) and lung and muscle tissue (significant vs., ad libitum-fed controls); no change was observed in kidney and heart tissue. To determine a potential mechanism of reduced hepatic IGF-I gene expression in uremia, the hepatic GH receptor gene expression in the same experimental animals was analyzed by specific solution hybridization/RNase protection assay. Uremic animals had a 20-30% reduction of hepatic GH receptor mRNA abundance compared with controls. Hepatic GHBP expression in uremia was decreased in parallel. Despite the reduction of hepatic IGF-I mRNA abundance, plasma IGF-I levels in uremia were not different from ad libitum-fed controls. This discrepancy is explained by an increased concentration of IGFBPs in uremic plasma. By RIA, plasma IGFBP-1 levels in uremia were increased 4-fold; by Western immunoblot, plasma IGFBP-2 levels were increased 7-fold and plasma IGFBP-4 levels were increased 2-fold compared with both control groups. Intact IGFBP-3 (M(r), approximately 48 kDa) and low molecular IGFBP-3 fragments were not significantly different among the three groups. By Northern blot analysis, hepatic IGFBP-1 mRNA levels in uremia were 2-fold higher than in controls. IGFBP-2 mRNA abundance in liver tissue was increased 4-fold, whereas in kidney there was a significant reduction of IGFBP-2 mRNA (30% of control). IGFBP-4 mRNA was increased by 50% in kidney but not in liver. Plasma insulin and corticosterone levels were not different among the groups. Our study shows that hepatic IGF-I gene expression was specifically reduced in uremia, partially as the consequence of a reduced hepatic GH receptor gene expression. One of the mechanisms contributing to increased IGFBP levels in uremia is increased hepatic gene expression of IGFBP-1 and IGFBP-2. The imbalance between reduced hepatic IGF-I production and increased hepatic IGFBP-1 and 2 production is likely to play a pathogenic role for catabolism and growth failure in CRF.
‘Molten‐globule state’: a compact form of globular proteins with mobile side‐chains (1983)

Side chain mobility of protein
Leaky ryanodine receptors in β-sarcoglycan deficient mice: a potential common defect in muscular dystrophy (2012)

Our data suggest that leaky RyR1 channels may underlie multiple forms of muscular dystrophy linked to mutations in genes encoding components of the dystrophin-glycoprotein complex. A common underlying abnormality in calcium handling indicates that pharmacological targeting of dysfunctional RyR1 could be a novel therapeutic approach to improve muscle function in Limb-Girdle and Duchenne muscular dystrophies.