gebhart/patrepeval huggingface dataset:
Expression of difficult‐to‐remove host cell protein impurities during extended Chinese hamster ovary cell culture and their impact on continuous bioprocessing (2014)

During biopharmaceutical manufacturing, Chinese hamster ovary (CHO) cells produce hundreds of extracellular host cell protein (HCP) impurities, which must be removed from the therapeutic product by downstream purification operations to ensure patient safety. A subset of 118 of these HCPs have been reported as exceptionally difficult to remove during downstream purification because they co-purify due to retention characteristics on chromatographic media and/or product-association through strongly attractive interactions to the therapeutic protein. As the biopharmaceutical industry moves towards continuous bioprocessing, it is important to consider the impact of extended culture of CHO cells on the expression of extracellular HCP impurities, especially those HCPs known to challenge downstream purification. Two complementary proteomic techniques, two-dimensional electrophoresis (2DE) and shotgun, were applied to detect variations in the extracellular CHO HCP profile over 500 days of culture. In total, 92 HCPs exhibited up to 48-fold changes in expression, with 34 of these HCPs previously reported as difficult to purify. Each proteomic technique detected differential expression by a distinct set of HCPs, with 10 proteins exhibiting significant variable expression by both methods. This study presents the impact of cell age on the extracellular CHO HCP impurity profile and identifies HCPs with variable expression levels, which warrant further investigation to facilitate their clearance in downstream purification.
Effects of Incremental Infusions of Arginine Vasopressin on Adrenocorticotropin and Cortisol Secretion in Man* (1988)

Arginine vasopressin (AVP) regulates ACTH release under certain conditions, and exogenously administered AVP is used clinically to stimulate ACTH secretion. We attempted to determine at what plasma concentration AVP can stimulate ACTH release. Six normal men were given infusions of AVP (Ferring) or vehicle between 1600 and 1700 h on five occasions: 1) saline (30 mL/h); 2) 10 ng AVP/min; 3) 30 ng AVP/min; 4) 100 ng AVP/min; and 5) 300 ng AVP/min. Plasma AVP, ACTH, and cortisol concentrations were measured every 10 min during the infusions. Basal plasma AVP levels were less than 1 ng/L (less than 0.92 pmol/L). The lowest AVP dose raised plasma AVP into the range found in fluid-deprived subjects (7-8 ng/L;6.5-7.3 pmol/L), but had no effect on plasma ACTH concentrations. AVP in a dose of 30 ng/min also had no effect. The 100 ng AVP/min dose raised plasma AVP concentrations to 51.4-65.5 ng/L (46-60 pmol/L). This increase led to a transient insignificant increase in plasma ACTH from 13.9 +/- 1.2 (+/- SEM) ng/L (3.1 +/- 0.3 pmol/L) to 20.0 +/- 1.4 ng/L (4.4 +/- 0.3 pmol/L), while plasma cortisol rose significantly from 146 +/- 10 to 209 +/- 19 nmol/L (P less than 0.01) after 60 min of infusion. The 300 ng AVP/min dose raised plasma AVP levels to about 260 ng/L (239 pmol/L); the maximal plasma ACTH and cortisol levels were 39.5 +/- 5.0 ng/L (8.7 +/- 1.1 pmol/L; P less than 0.01) and 348 nmol/L (P less than 0.01), respectively. Thus, peripheral plasma AVP levels have to be raised high above the physiological range before ACTH release is stimulated. We conclude that any AVP reaching the adenohypophysis through the peripheral circulation is of much less importance for the regulation of ACTH secretion than is AVP derived from the pituitary portal circulation.
Infrared Absorbing Croconaine Dyes:  Synthesis and Metal Ion Binding Properties (2007)

Quinaldine-based croconaine dyes synthesized by the condensation reaction between croconic acid and the respective quinaldinium salts are described. These dyes exhibit absorption maximum in the infrared region (840-870 nm) with high molar extinction coefficients (1-5 x 10(5) M(-1) cm(-1)) and have very low fluorescence quantum yields. Upon binding to divalent metal ions, these dyes were found to form complexes with a 2:1 stoichiometry having high association constants of the order of 10(11)-10(14) M(-2), while the monovalent metal ions showed negligible affinity. The binding of the croconaine dye 3d with divalent metal ions especially Zn(2+), Pb(2+), and Cd(2+) led to significant chelation-enhanced fluorescence emission. The broadening of the aromatic signals, vinylic and N-methyl protons and the negligible changes at the aliphatic region of the dye 3d in the (1)H NMR spectrum in the presence of Zn(2+), indicate that the binding occurs at the carbonyl groups of the croconyl ring. The shift in the croconyl carbonyl stretching frequency in the [3d-Zn(2+)] complex analyzed through FT-IR analysis further confirms the involvement of two electron-rich carbonyl groups of the croconyl moiety in the complexation. These results demonstrate that the binding of the divalent metal ions at the carbonyl oxygens of these infrared absorbing dyes can be favorably utilized for the development of potential sensors for the detection of metal ions and further can be exploited as sensitizers for photodynamic therapeutic applications.
Some Effects of Lumbar Support Contour on Driver Seated Posture (1995)

&lt;div class="htmlview paragraph"&gt;An appropriately contoured lumbar support is widely regarded as an essential component of a comfortable auto seat. A frequently stated objective for a lumbar support is to maintain the sitter's lumbar spine in a slightly extended, or lordotic, posture. Although sitters have been observed to sit with substantial lordosis in some short-duration testing, long-term postural interaction with a lumbar support has not been documented quantitatively in the automotive environment. A laboratory study was conducted to investigate driver posture with three seatback contours. Subjects&lt;span class="xref"&gt;†&lt;/span&gt; from four anthropometric groups operated an interactive laboratory driving simulator for one-hour trials. Posture data were collected by means of a sonic digitizing system. The data identify driver-selected postures over time for three lumbar support contours. An increase of 25 mm in the lumbar support prominence from a flat contour did not substantially change lumbar spine posture.&lt;/div&gt;
Effects of smoking on healing response to non‐surgical periodontal therapy: a multilevel modelling analysis (2009)

Multilevel analysis was applied on periodontal treatment response data. Smokers showed less favourable PPD reduction at deep sites after non-surgical periodontal therapy.
A personalized Web search engine using fuzzy concept network with link structure (2002)

There has been much research on link-based search engines such as google and clever. They use link structure to find precision result. Usually, a link-based search engine produces higher-quality results than a text-based search engine. However, they have difficulty in producing the result fit to a specific user's preference. Personalization is required to support a more appropriate result. Among many techniques, the fuzzy concept network based on a user profile can represent a user's subjective interest properly. The paper presents another search engine that uses the fuzzy concept network to personalize the results from a link-based search method. The fuzzy concept network based on a user profile reorders five results of the link-based search engine, and the system provides a personalized high-quality result. Experimental results with three subjects indicate that the system developed searches not only relevant but also personalized Web pages on a user's preference.
Proton binding by linear, branched, and hyperbranched polyelectrolytes (2010)

This article reviews our understanding of ionization processes of weak polyelectrolytes. The emphasis is put on a general introduction to site binding models, which are able to account for many experimental features of linear and branched polyelectrolytes, including dendrimers. These models are fully compatible with the classical description of acid–base equilibria. The review further discusses the nature of the site–site interaction and role of conformational equilibria. Experimental charging data of numerous weak polyelectrolytes are discussed in terms of these models in detail.
Thermal Studies of In-Vivo Vascular Tissue Fusion by Argon Laser (1988)

There are conflicting opinions regarding the mechanism of welding or fusion of vascular tissue by lasers. In this study, we measured the effects of saline irrigation on tissue temperature and fusion produced by argon laser welding of eight femoral and four carotid arteriovenous fistulas. Temperatures were continuously recorded using a digital thermographic camera. Forty 1-cm. welds were performed using powers of 0.50 (n = 24), 0.75 (n = 8), and 1.00 (n = 8) watt (W), with an energy fluence of 1100 J/cm2 per 1 cm segment, and cooling of the anastomotic site by saline irrigation (3 ml/minute). The "success" of fusions was determined by testing integrity of the repairs by exposure to blood flow. At 0.50 and 0.75 W, successful welds were formed when the temperatures were 44.2 +/- 1.6 (n = 28) and 55.0 +/- 3.6 degrees C (n = 20), with maximum temperatures of 47.9 and 59.9 degrees C respectively. At 1 W, the tissue was desiccated and the welds disrupted when exposed to blood flow with temperatures measured at 63.7 +/- 10.0 degrees C (n = 22) and maximum of 88.0 degrees C. Eight welds were also attempted without saline irrigation at 0.25 (n = 4) and 0.50 W (n = 4). At 0.25 W, tissue fusion was achieved but disrupted when exposed to intraluminal pressures with temperatures 50.3 +/- 2.0 degrees C (n = 10) and maximum of 52.6 degrees C. At 0.50 W, the fusion failed after only minimal exposure to the laser energy because of tissue drying and retraction with temperatures measured at greater than 125 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Proliferation of Pulmonary Interstitial Fibroblasts Is Mediated by Transforming Growth Factor-β1-induced Release of Extracellular Fibroblast Growth Factor-2 and Phosphorylation of p38 MAPK and JNK (2005)

Idiopathic pulmonary fibrosis (IPF; a progressive lung disease) is characterized by parenchymal remodeling with enlarged air spaces called honeycomb cysts and palisades of fibroblasts called fibroblast foci. In IPF, lung epithelial cells covering honeycomb cysts and fibroblast foci aberrantly express the active conformation of the potent fibrogenic cytokine transforming growth factor-beta1 (TGF-beta1). Using explanted rat lung slices, we transfected alveolar epithelial cells with the retrovirus pMX containing a site-directed mutation in which Cys223 and Cys225 were substituted with serines, resulting in release of biologically active TGF-beta1 and fibroblast proliferation and remodeling that resembled IPF. Fibroblasts obtained from transfected explants and in culture for 6 weeks incorporated 6.59 +/- 1.55-fold more [3H]thymidine compared with control fibroblasts without transfection or fibroblasts obtained from transfected explants cultured with antibody to fibroblast growth factor-2 (FGF-2). Primary lung fibroblasts obtained from normal rat lungs cultured with TGF-beta1 expressed increased levels of phosphorylated p38 MAPK and JNK, but not ERK1/2. The presence of TGF-beta1 caused an immediate release of extracellular FGF-2 from primary pulmonary fibroblasts; and in the presence of anti-FGF-2 antibody, phosphorylated p38 MAPK and JNK were abrogated. TGF-beta inhibits cell proliferation by suppression of c-Myc and induction of p15INK46, p21CIP1, or p27KIP. Fibroblasts cultured with TGF-beta1 showed no regulation of c-Myc or induction of p15INK46, p21CIP1,or p27KIP. These findings suggest that pulmonary fibroblasts may not respond to the anti-proliferative effects of TGF-beta1, but proliferate in response to TGF-beta1 indirectly by the release of FGF-2, which induces phosphorylation of p38 MAPK and JNK.
Thrombopoietin, but not erythropoietin promotes viability and inhibits apoptosis of multipotent murine hematopoietic progenitor cells in vitro (1996)

The recently cloned c-mpl ligand, thrombopoietin (Tpo), has been extensively characterized with regard to its ability to stimulate the growth, development, and ploidy of megakaryocyte progenitor cells and platelet production in vitro and in vivo. Primitive hematopoietic progenitors have been shown to express c-mpl, the receptor for Tpo. In the present study, we show that Tpo efficiently promotes the viability of a subpopulation of Lin-Sca-1+ bone marrow progenitor cells. The ability of Tpo to maintain viable Lin-Sca-1+ progenitors was comparable to that of granulocyte colony-stimulating factor and interleukin-1, whereas stem cell factor (SCF) promoted the viability of a higher number of Lin-Sca-1+ progenitor cells when incubated for 40 hours. However, after prolonged (> 40 hours) preincubation, the viability-promoting effect of Tpo was similar to that of SCF. An increased number of progenitors surviving in response to Tpo had megakaryocyte potential (37%), although almost all of the progenitors produced other myeloid cell lineages as well, suggesting that Tpo acts to promote the viability of multipotent progenitors. The ability of Tpo to promote viability of Lin-Sca-1+ progenitor cells was observed when cells were plated at a concentration of 1 cell per well in fetal calf serum-supplemented and serum-depleted medium. Finally, the DNA strand breakage elongation assay showed that Tpo inhibits apoptosis of Lin-Sca-1+ bone marrow cells. Thus, Tpo has a potent ability to promote the viability and suppress apoptosis of primitive multipotent progenitor cells.
Vascular Endothelial Growth Factor-Related Pathways in Hemato-Lymphoid Malignancies (2010)

Angiogenesis is essential for malignant tumor growth. This has been documented for solid tumors, and there is an emerging evidence suggesting that tumor progression of hematolymphoid malignancies also depends on the induction of new blood vessel formation. The most important proangiogenic agent is vascular endothelial growth factor (VEGF), activating VEGF receptors 1 and 2. The available data on angiogenesis in hemato-lymphoid malignancies, such as acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, multiple myeloma, and lymphomas, point towards the significance of autocrine and paracrine VEGF-mediated effects for proliferation and survival of leukemia/lymphoma cells in addition to tumor vascularization. Antiangiogenic strategies have become an important therapeutic modality for solid tumors. Several antiangiogenic agents targeting VEGF-related pathways are also being utilized in clinical trials for the treatment of hemato-lymphoid malignancies, and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hemato-lymphoid malignancies and the translation of such basic findings into clinical studies.
Factor IX Activation by Factor XIa Proceeds without Release of a Free Intermediate (1997)

Factor IX activation by factor XIa is thought to proceed through the singly-cleaved free intermediate, factor IX alpha. However, we observed no intermediate development during factor IX activation by factor XIa when using a low substrate to enzyme ratio (44:1 mol/mol). This result can be explained by one of two mechanisms: (1) factor XIa-catalyzed activation proceeds via a singly-cleaved free intermediate with a much higher efficiency of cleavage than factor IX zymogen, or (2) the reaction occurs without free intermediate generation, whereby factor XIa makes both proteolytic cleavages in a single substrate molecule before releasing the final product (processive mechanism). We compared the factor XIa cleavage rates of free factor IX alpha and factor IXa alpha with that of factor IX zymogen. In contrast to the requirements of mechanism (1), the cleavage rate constants of factor IX zymogen, factor IX alpha, and factor IXa alpha were similar: 0.38 +/- 0.02 s(-1), 0.34 +/- 0.05 s(-1), and 0.27 +/- 0.01 s(-1), respectively. It seems likely that factor XIa-generated intermediates observed under some reaction conditions are produced through the occasional failure of a processive mechanism. Indeed, in reactions using a high substrate to enzyme ratio (1900:1 mol/mol), we observed some factor IX alpha development; however, the pattern of intermediate and product development over time was inconsistent with a mechanism involving an obligate intermediate. Rather, it corresponded to behavior expected from a processive mechanism undergoing a consistent low failure. We conclude that factor XIa-catalyzed activation of factor IX proceeds via a processive mechanism without release of a free intermediate.
On the Action of Methotrexate and 6-Mercaptopurine on M. avium Subspecies paratuberculosis (2007)

We show that methotrexate and 6-MP inhibit MAP growth in vitro. Each of the four isolates manifests different % -DeltacGI. These data are compatible with the hypothesis that the clinical improvement in patients with IBD treated with methotrexate and 6-MP could be due to treating a MAP infection. The decrease in pro-inflammatory cytokines, thought to be the primary mechanism of action, may simply be a normal, secondary, physiological response. We conclude that henceforth, in clinical studies that evaluate the effect of anti-MAP agents in IBD, the use of methotrexate and 6-MP should be excluded from any control groups.
56‐1: Invited Paper: Research on Commercial Foldable AMOLED and Relevant Technologies (2020)

In this work, a commercial foldable display of 8.0‐inch 2K AMOLED(Active Matrix Organic Light‐emitting Diode) was developed for foldable smart phones. By considering commercial requirements for a brand new product, fundamental performances are introduced. By new design concepts, display and touch performances are guaranteed, while the foldable reliabilities are also achieved to a commercial goal. Not only how to improve the bending abilities, but also the mechanical abilities of foldable display module are discussed. In bending performance, the endurance of dynamic folding and static folding are treated by different ways. The materials and layer stacks optimization are discussed. The root causes of the deformation in foldable display are analyzed. Solutions for the out‐folding display is suggested.
Multi-Object Auctions: Sequential vs. Simultaneous Sales (1986)

Would a seller prefer to sell multiple objects through sequential or simultaneous auctions? Sequential auctions with bids announced between sales seem preferable because the bids may convey information about the value of objects to be sold later. The auction literature shows that this information effect increases the seller’s expected revenue. However, there is also a deception effect which develops in the sequential sales. If a bidder knows that his current bid will reveal information about later objects then he has an incentive to underbid. These two opposing effects are studied in a two-signal model. The results show that either effect may dominate the other, leading the seller to sometimes prefer simultaneous sales and to sometimes prefer sequential sales. The winner's curse can explain this ordering.
Synaptic Dysfunction in Depression: Potential Therapeutic Targets (2012)

Basic and clinical studies demonstrate that depression is associated with reduced size of brain regions that regulate mood and cognition, including the prefrontal cortex and the hippocampus, and decreased neuronal synapses in these areas. Antidepressants can block or reverse these neuronal deficits, although typical antidepressants have limited efficacy and delayed response times of weeks to months. A notable recent discovery shows that ketamine, a N-methyl-D-aspartate receptor antagonist, produces rapid (within hours) antidepressant responses in patients who are resistant to typical antidepressants. Basic studies show that ketamine rapidly induces synaptogenesis and reverses the synaptic deficits caused by chronic stress. These findings highlight the central importance of homeostatic control of mood circuit connections and form the basis of a synaptogenic hypothesis of depression and treatment response.
Simple model of optical amplifier chains to evaluate penalties in WDM systems (1998)

A simple model to evaluate the penalty due to amplifier gainshape in a wavelength division multiplexing (WDM) optical system is proposed. The model requires only knowledge of the overall gain of the amplifier chain for all channels and provides signal-to-noise ratio (SNR) penalties for given launched powers. It also provides the input power distribution required for SNR equalization, and the associated SNR penalty, by solving an eigenvalue/eigenvector problem. The penalty predicted by the model agrees well with recent field measurements on a transoceanic cable. The model can also be applied to predict the gainshape of the amplifier chain from a measurement of the output noise spectrum with no input signal. The capacity of a long amplifier chain can thereby be determined from the receiving terminal only.
Metabolism and pharmacokinetics of N1,N11-diethylnorspermine in a Cebus apella primate model. (2000)

The tissue distribution, metabolic profile, and pharmacokinetic parameters of i.v.-administered N1,N11-diethylnorspermine (DENSPM) are evaluated in Cebus apella primates, and the results are compared with data gathered from canine and human studies. Although the metabolic processing of DENSPM (i.e., deethylation and deaminopropylation) in dogs and primates is very similar, there are some significant differences in tissue distribution of the parent drug. In dogs, the organ concentration of DENSPM follows the order kidney >> liver approximately = lung > spleen. In the primate, the order is liver >> kidney approximately = spleen > lung. The difference in pharmacokinetic parameters between the species is profound with (area under the time-concentration curve)primate << (area under the time-concentration curve)dog; (terminal elimination half-life)primate << (terminal elimination half-life)dog; and (mean residence time)primate << (mean residence time)dog. The most notable difference between dogs and primates is seen in the fraction of parent drug excreted unchanged in the urine, 50% in the dog and < 1% in the primate. However, the pharmacokinetic parameters and urinary drug clearance in C. apella primates are remarkably similar to those in humans. Thus, C. apella is established as an excellent model for assessing the metabolism, tissue distribution, and pharmacokinetic properties of polyamine analogues.
Temporal decorrelation of short laser pulses (1998)

We describe a unique approach for extracting the temporal profile of ultrashort laser pulses from typical autocorrelation measurements. The use of the constraint that intensity is a nonnegative quantity enables an iterative numerical algorithm to reconstruct pulse shapes in a one-dimensional procedure. With the reconstruction of the intensity profile, the Gerchberg–Saxton algorithm can be used to retrieve the phase of the electric field from a spectral measurement. Because these procedures are carried out in one dimension, they are numerically much faster than two-dimensional techniques such as frequency-resolved optical gating. Their high computational efficiency can save substantial time by constructing good trial solutions for the more accurate but slower procedure of frequency-resolved optical gating.