gebhart/patrepeval huggingface dataset:
Folding and assembly of newly synthesized thyroglobulin occurs in a pre-Golgi compartment (1991)

We have investigated the kinetics of folding and dimerization of newly synthesized thyroglobulin (Tg), the precursor protein in the manufacture of thyroid hormone. From the examination of lysates of pulse-labeled cultured thyrocytes by denaturing and nondenaturing gel electrophoresis, we have found that the earliest detectable form of nascent Tg is a transient aggregate, whose dissolution in vitro requires the addition of a reducing agent. In vivo, aggregate dissolution occurs with a t1/2 approximately 10 min at 37 degrees C. By 10 min after synthesis, monomeric Tg is first detectable in a conformationally unstable form. Dimeric Tg is formed thereafter (t1/2 approximately 30 min), but well before arrival of the protein in the medial Golgi (t1/2 approximately 2 h). Certain metabolic inhibitors permit dimerization yet block transport of the dimer to the Golgi. Thus, Tg dimerization occurs in a pre-Golgi compartment, and other steps after dimerization are likely to be important in the process of exit from the endoplasmic reticulum (ER). Further, aggregate dissolution, as well as dimerization, are inhibited significantly at 15 degrees C, indicating thermal sensitivity of Tg folding over and above effects on vesicular transport. Inhibitors of Tg iodination have no effect on Tg dimerization or Golgi arrival. Pretreatment of thyrocytes with thyroid-stimulating hormone substantially accelerates Tg flux through the ER, by increasing the amount, as well as the rate, of Tg transport, possibly at the expense of a small fraction of Tg that appears refractory to dimerization. Inhibition of N-linked glycosylation by tunicamycin causes a complete block in intracellular Tg transport by inducing the formation of biologically irreversible aggregates, suggesting that glycosylation of Tg serves to prevent denaturation of the secretory protein within the ER lumen.
Practical and Useful Methods for the Enantioselective Reduction of Unsymmetrical Ketones (1992)

Enantioselective reduction of unsymmetrical ketones to optically active alcohols is very important in organic synthesis. Catalytic methods have been developed for this process and have not been reviewed previously. In this article the recently developed oxazaborolidine catalyzed reduction along with other useful reagents will be discussed. 1. Introduction 2. Oxazaborolidines 3. B-3-pinanyl-9-borabicyclo[3.3.1]nonane 4. Chlorodiisopinocampheylborane 5. 2,5-Dimethylborolane 6. BINAL-H 7. BINAP-Ru Complex 8. Conclusion
Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract (2016)

The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue penetration and retention.
CD20 is a molecular target for scFvFc:zeta receptor redirected T cells: Implications for cellular immunotherapy of CD20+ malignancy (1998)

The CD20 molecule was evaluated as a B-cell lymphoma target epitope for T cells expressing a CD20-specific single-chain FvFc-zeta (scFvFc:zeta) chimeric receptor. A cDNA construct consisting of a murine kappa leader sequence, CD20-specific scFv, human immunoglobulin (Ig) G1 hinge-C(H)2-C(H)3, the human CD4 transmembrane, and the intracellular signaling domain of the human CD3 complex's zeta chain was synthesized by polymerase chain reaction splice-overlap extension. The human CD4+ Jurkat cell line was electroporated with the CD20-specific scFvFc:zeta construct cloned into the mammalian expression vector pcDNAneo. Western blot analysis of transfectant whole cell lysate with an anti-zeta antibody demonstrated the expression of both endogenous zeta and the chimeric receptor protein, with a mobility consistent with the expected molecular weight of 66 kD under reducing conditions; nonreduced lysate revealed a chimeric receptor complex of approximately 132 kD. The scFvFc:zeta receptor was present on the cell surface as detected by flow cytometry of T-cell transfectants stained with an anti-mouse Fab-specific antibody and anti-human Fc gamma-specific monoclonal antibody. Coculture of Jurkat transfectants with CD20+ lymphoma cells resulted in the accumulation of interleukin (IL)-2 in culture supernatants as detected by ELISA. IL-2 production was triggered by the specific interaction between the CD20 molecule and the scFvFc:zeta as IL-2 was not detected in cultures with mock transfected Jurkat cells or CD20- stimulator cells. Furthermore, IL-2 production was inhibited by the addition of a soluble anti-CD20 monoclonal antibody to cocultured Jurkat transfectants and CD20+ stimulator cells. The capacity of CD20 to trigger the lytic machinery of scFvFc:zeta-expressing cytotoxic T lymphocytes (CTLs) was assessed using the murine allo-specific CD8+ CTL clone 2c. CD20-specific redirected cytolytic activity against human lymphoma targets was observed with 2c transfectants in a 4-hour chromium release assay. These results demonstrate that CD20 can serve as a target epitope for scFvFc:zeta receptor-expressing T cells.
Bacterial Biofilms: Development, Dispersal, and Therapeutic Strategies in the Dawn of the Postantibiotic Era (2013)

Biofilm formation constitutes an alternative lifestyle in which microorganisms adopt a multicellular behavior that facilitates and/or prolongs survival in diverse environmental niches. Biofilms form on biotic and abiotic surfaces both in the environment and in the healthcare setting. In hospital wards, the formation of biofilms on vents and medical equipment enables pathogens to persist as reservoirs that can readily spread to patients. Inside the host, biofilms allow pathogens to subvert innate immune defenses and are thus associated with long-term persistence. Here we provide a general review of the steps leading to biofilm formation on surfaces and within eukaryotic cells, highlighting several medically important pathogens, and discuss recent advances on novel strategies aimed at biofilm prevention and/or dissolution.
Investigations on Pantothenic Acid and Its Related Compounds: IX. Biochemical Studies (4).* Separation and Substrate Specificity of Pantothenate Kinase and Phosphopantothenoylcysteine Synthetase** (1967)

1. To investigate the pathway of biosynthesis of Co A in rat liver, pantothenate kinase [EC 2.7.1.33] and phosphopantothenoylcysteine synthetase [EC 6.3.2.5] have been completely separated from each other. 2. Based on the specificity of these two separate enzymes, it was suggested that pantothenate was first phosphorylated and then condensed with cysteine to form phosphopantothenoylcysteine in the course of CoA biosynthesis in rat liver. 3. It has been shown that rat-liver pantothenate kinase catalyzes the phosphorylation not only of pantothenate and panteth(e)ine but also of pantothenoylcyst(e)ine.
DHE in the Pharmacotherapy of Migraine: Potential for a Larger Role (2006)

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms.
Cytosolic Phospholipase A2: Targeting Cancer through the Tumor Vasculature (2009)

These findings identify cPLA2 as a novel molecular target for tumor sensitization to radiation therapy through the tumor vasculature.
Image segmentation on spiral architecture (2001)

Spiral Architecture is a relatively new and powerful approach to general purpose machine vision system. It contains very useful geometric and algebraic properties. Two algebraic operations, Spiral Addition and Spiral Multiplication, have been defined on it. This paper presents a way to segment the object(s) in an image uniformly by Spiral Multiplication. Namely, a number of analogous small copies of the original object(s) are made during segmentation. An algorithm is also developed in this paper to compute the scaling factor or the number of the small copies, so image segmentation can be done flexibly and quantitatively according to the specific application. The research results are very beneficial to image segmentation in parallel image processing and distributed image processing.
Three dimensional interconnects with high aspect ratio TSVs and fine pitch solder microbumps (2009)

High density three dimensional (3D) interconnects formed by high aspect ratio through silicon vias (TSVs) and fine pitch solder microbumps are presented in this paper. The aspect ratio of the TSV is larger than 10 and filled with Cu without voids; there are electrical nickel and immersion gold (ENIG) pads on top of the TSV as under bump metallurgy (UBM) layer. On the Si chip, Cu/Sn solder microbumps with 16µm in diameter and 25µm in pitch are fabricated. After singulating the Si chip and the Si carrier, there are joined together and the interconnection is formed between them through the solder micro bumps and the TSV.
Antibiotic bead production. (2000)

We are reporting a practical technique for the production of antibiotic beads for use in combating musculoskeletal infections. The technique utilizes bead molds with tobramycin powder mixed with polymethylmethacrylate on twisted wire strands to produce strands of 25 beads of various sizes. These beads are gas sterilized and available for use "off the shelf" in a manner that is much more efficient than traditional production by hand on the back table in the operating room. Our technique was also utilized at a second institution to demonstrate its efficacy at another site.
Singularity-Free Fully-Isotropic Translational Parallel Mechanisms (2002)

Parallel mechanisms show desirable characteristics such as a large payload to robot weight ratio, considerable stiffness, low inertia and high dynamic performances. In particular, parallel manipulators with fewer than six degrees of freedom have recently attracted researchers' attention, as their employ may prove valuable in those applications in which a higher mobility is uncalled-for. The attention of this paper is focused on translational parallel mechanisms (TPMs), that is on parallel mechanisms whose output link (platform) is provided with a pure translational motion with respect to the frame. It deals with the general problem of the topological synthesis and classification of TPMs and it investigates both their constraint and direct singularities. In particular, it identifies for the first time special families of fully-isotropic mechanisms. Such manipulators exhibit outstanding properties, as they are free from singularities and show a constant orthogonal Jacobian matrix throughout their workspace. As a consequence, both the direct and the inverse position problems are linear and the kinematic analysis proves straightforward.
Quantitation of Hydroxyl Radicals Produced by Radiation and Copper-Linked Oxidation of Ascorbate by 2-Deoxy-d-Ribose Method (1997)

We have established controlled conditions for studying the reaction of chemically and radiolytically produced hydroxyl radical (.OH) with 2-deoxy-D-ribose (2-DR). Ascorbate (ASC) or dithiothreitol (DTT) and cuprous or cupric ions were used to generate the OH-radical. The OH-radical was detected using the classical method of measuring the amount of thiobarbituric acid reactive products (TBARP) formed by .OH-mediated 2-DR degradation, but using sensitive fluorescent detection of the TBARP production to quantify the OH-radical. All experiments were performed with adequate O(2) concentrations. The copper reaction with ASC consumes O(2) in a manner that is strongly dependent on copper concentration, and less dependent on ascorbate concentration. For an independent check of the Cu2+ catalyzed ASC oxidation kinetics, the decay of ASC absorbency at 265 nm, as well as the increase of H(2)O(2) absorbency at approximately 240 nm, were also monitored. These spectral changes agree well with the O(2) consumption data. TBARP production from 2-DR incubated with a Cu2+-ASC mixture or gamma-irradiated were also compared. gamma-Irradiation of 2-DR solutions shows a dose and 2-DR concentration dependent increase of TBARP generation. Other electron donors, such as DTT, are more complicated in their mechanism of OH-radical production. Incubation of 2-DR with Cu2+-DTT mixtures shows a delay (approximately 50 min) before OH-radical generation is detected. Our results suggest that the Cu2+-ASC reaction can be used to mimic the effects of ionizing radiation with respect to OH-radical generation. The good reproducibility and relative simplicity of the 2-DR method with fluorescence detection indicates its usefulness for the quantitation of the OH-radical generated radiolytically or chemically in carefully controlled model systems.
Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury (2000)

The data are consistent with an acute inflammatory component of TBI in children and suggest an association between cerebrospinal fluid IL-8 and outcome after TBI. IL-8 may represent a potential target for anti-inflammatory therapy.
Probing the Limits of Aptamer Affinity with a Microfluidic SELEX Platform (2011)

Nucleic acid-based aptamers offer many potential advantages relative to antibodies and other protein-based affinity reagents, including facile chemical synthesis, reversible folding, improved thermal stability and lower cost. However, their selection requires significant time and resources and selections often fail to yield molecules with affinities sufficient for molecular diagnostics or therapeutics. Toward a selection technique that can efficiently and reproducibly generate high performance aptamers, we have developed a microfluidic selection process (M-SELEX) that can be used to obtain high affinity aptamers against diverse protein targets. Here, we isolated DNA aptamers against three protein targets with different isoelectric points (pI) using a common protocol. After only three rounds of selection, we discovered novel aptamer sequences that bind to platelet derived growth factor B (PDGF-BB; pI = 9.3) and thrombin (pI = 8.3) with respective dissociation constants (K(d)) of 0.028 nM and 0.33 nM, which are both superior to previously reported aptamers against these targets. In parallel, we discovered a new aptamer that binds to apolipoprotein E3 (ApoE; pI = 5.3) with a K(d) of 3.1 nM. Furthermore, we observe that the net protein charge may exert influence on the affinity of the selected aptamers. To further explore this relationship, we performed selections against PDGF-BB under different pH conditions using the same selection protocol, and report an inverse correlation between protein charge and aptamer K(d).
Seroepidemiological study of relationships between Epstein-Barr virus and rheumatoid arthritis. (1981)

To elucidate the relationship between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA), we measured antibodies to RA-associated nuclear antigen (anti-RANA) and three other EBV-related antigens in the sera of RA patients and controls. Our study groups consisted of 89 patients with definite or classical RA, mean age 56, male/female ratio 47:42; and 53 normal and osteoarthritis controls, mean age 51, male/female ratio 25:28. In addition to anti-RANA, we measured antibodies to viral capsid antigen (anti-VCA), early antigen (anti-EA) and EBV-associated nuclear antigen (anti-EBNA). Anti-RANA was detected in 71% of RA patients but in only 6% of controls. Elevated anti-VCA titers (greater than 1:160) were more common in RA patients than controls, 31% compared with 15%. The geometric mean titer of anti-VCA was significantly higher iun the RA group, 133 compared with 58. Anti-EA was present in 53% of RA patients but only 19% of controls. Anti-EA in elevated titers (greater than 1:20) was present in 26% of RA patients but only 7% of controls. Characterization of the anti-EA antibodies revealed that the RA patients reacted primarily with the diffuse component, whereas the majority of the controls reacted with the restricted component of the EA complex. In contrast, the frequencies, distributions, and geometric mean titers of anti-EBNA were not significantly different between the two groups. Correlative analysis of these antibodies showed highly significant relationships between anti-VCA and anti-EA, and anti-RANA and anti-EBNA in the RA group. These data are compatible with the interpretation that RA patients have either more active EBV infections than controls or an altered regulation of their immune response to this infectious agent.
Unesterified Cholesterol Accumulation in Late Endosomes/Lysosomes Causes Neurodegeneration and Is Prevented by Driving Cholesterol Export from This Compartment (2011)

While unesterified cholesterol (C) is essential for remodeling neuronal plasma membranes, its role in certain neurodegenerative disorders remains poorly defined. Uptake of sterol from pericellular fluid requires processing that involves two lysosomal proteins, lysosomal acid lipase, which hydrolyzes C esters, and NPC1 (Niemann-Pick type C1). In systemic tissues, inactivation of either protein led to sterol accumulation and cell death, but in the brain, inactivation of only NPC1 caused C sequestration and neurodegeneration. When injected into the CNS of the npc1(-/-) mouse, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), a compound known to prevent this C accumulation, diffused throughout the brain and was excreted with a t(&frac12;) of 6.5 h. This agent caused suppression of C synthesis, elevation of C esters, suppression of sterol regulatory-binding protein 2 (SREBP2) target genes, and activation of liver X receptor-controlled genes. These findings indicated that HP-β-CD promoted movement of the sequestered C from lysosomes to the metabolically active pool of C in the cytosolic compartment of cells in the CNS. The ED(50) for this agent in the brain was ∼0.5 mg/kg, and the therapeutic effect lasted >7 d. Continuous infusion of HP-β-CD into the ventricular system of npc1(-/-) animals between 3 and 7 weeks of age normalized the biochemical abnormalities and completely prevented the expected neurodegeneration. These studies support the concept that neurons continuously acquire C from interstitial fluid to permit plasma membrane turnover and remodeling. Inactivation of NPC1 leads to lysosomal C sequestration and neurodegeneration, but this is prevented by the continuous, direct administration of HP-β-CD into the CNS.
Design and experiments with a 30 DOF robot (2002)

A 30 degree-of-freedom (DOF) planar hyper-redundant manipulator is constructed in order to validate and demonstrate the authors' previous work on a framework for hyper-redundant robot kinematic analysis and algorithm development. The implementation of this robot is reviewed, and experimental work in hyper-redundant manipulation, obstacle avoidance, and locomotion is summarized. Potential benefits of high-DOF manipulators include superior obstacle avoidance ability, increased robustness with respect to mechanical failure, and the ability to perform new forms of robot locomotion and grasping.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Autoimmunity and Immunotherapy for Cancer (2006)

Adjuvant treatment for patients after resection of high-risk and regionally metastatic melanoma remains suboptimal. Despite the Food and Drug Administration's approval of high-dose interferon alfa-2b, the substantial toxicity of the therapy and the fact that its benefit is limited to 20 to 30 percent of patients at risk have hindered its general acceptance.Attempts to identify patients who benefit from adjuvant treatment with interferon alfa-2b have been disappointing to date. Although analyses of individual studies suggest that the benefit of high-dose interferon alfa-2b might be restricted to certain subgroups of patients, on the basis of the number of melanoma-involved lymph . . .
Evaluation of lipid extraction and fatty acid composition of human plasma (2010)

AIM: The objective of this study was to compare the efficiency of lipid extraction and to evaluate the fatty-acid composition in total lipids from human plasma, using a new technique and the established Folch, Lees and Stanley (FLS), Bligh and Dyer (BD), Rose-Gottlieb (RG), and Gerber (GM) methods. METHOD: A new technique, the alternative method, to extract total lipids using a microwave was proposed and evaluated. RESULTS: The total lipids extracted from human plasma varied between 0.19% and 0.41%; the highest total lipid extracted were obtained by the Folch, Lees and Stanley (0.41%), alternative method (0.37%) and Rose-Gottlieb (0.36%) methods. The Gerber method was ineffective to extract total lipids from human plasma. A total of 24 fatty-acid species were quantified by gas chromatography. Of the methods studied, the highest concentrations were found using the Folch, Lees and Stanley method (p < 0.05). CONCLUSION: The alternative method is a fast lipid-extraction technique that can be used for the identification of human plasma fatty acids, but it is not suitable for their measurement.
CCL17 and CCL22 attenuate CCL5‐induced mast cell migration (2005)

These results suggest that CCL5-induced migration of MCs via CCR4 can be regulated by the natural agonists CCL17 and CCL22, which are up-regulated at sites of allergic inflammation.
miRNAs as molecular biomarkers of cancer (2010)

miRNAs are noncoding RNAs that regulate gene expression. The advent of high-throughput techniques has revealed that miRNA expression is deregulated in almost all human tumors (both solid and hematologic) with respect to the normal tissue counterpart. These differences frequently recur in tumor-specific miRNA signatures, which are very helpful to diagnose the tissue of origin of the neoplasia, and sometimes also specific tumor subtypes. Increasing evidence also supports a role for miRNAs as prognostic biomarkers of human cancers. Finally, miRNAs are differentially expressed in the blood of cancer patients versus healthy donors, providing a rationale for the detection of miRNAs and diagnostic and prognostic circulating biomarkers.