gebhart/patrepeval huggingface dataset:
Akt Is a Key Modulator of Endothelial Progenitor Cell Trafficking in Ischemic Muscle (2007)

Trafficking of transplanted endothelial progenitor cells (EPCs) to ischemic tissue is enhanced by stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF). However, it has not been studied how these cytokines modulate the local milieu to entrap EPCs. This study was performed to elucidate a molecular pathway of trafficking EPCs through Akt and to test its application as an adjuvant modality to increase EPC homing. In a mouse hind limb ischemia model, systemically administered 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled mouse EPCs showed three stages of homing to ischemic limb: adhesion to endothelial cells (ECs), incorporation to capillary, and transendothelial migration into extravascular space. As an underlying mechanism to control adhesion of EPCs to ECs, we found that Akt was activated in ECs of ischemic muscle by ischemia-induced VEGF and SDF-1. In vitro and in vivo experiments using adenoviral vector for constitutively active or dominant-negative Akt genes showed that activated Akt enhanced intercellular adhesion molecule 1 (ICAM-1) expression on ECs. Akt activation in ECs also enhanced EPC incorporation to ECs and transendothelial migration in vitro experiments. Activated Akt was sufficient for induction of EPC homing even in normal hind limb, where VEGF or SDF-1 was not increased. Finally, local Akt gene transfer to ischemic limb significantly enhanced homing of systemically administered EPCs, new vessel formation, blood flow recovery, and tissue healing. Akt plays a key role in EPC homing to ischemic limb by controlling ICAM-1 and transendothelial migration. Modulation of Akt in the target tissue may be an adjunctive measure to enhance homing of systemically administered stem cells, suggesting a possibility of cell-and-gene hybrid therapy. Disclosure of potential conflicts of interest is found at the end of this article.
Isolation and Characterization of an Extracellular Lipase from the Conidia of Neurospora cvassa (1987)

A triacylglycerol lipase (EC 3.1.1.3) from the conidia of Neurospora crassa was purified and characterized. The enzyme was purified by Sephadex G-100 column chromatography. Homogeneity was checked by PAGE, and isoelectric focusing gave a single band corresponding to a pI of 6.4. The enzyme had an apparent Mr 54000 +/- 1000 as determined by gel filtration. SDS-PAGE gave a single band of Mr 27000, suggesting the presence of two identical subunits. This lipase preferred triglycerides with C16- and C18-fatty acyl chains. It cleaved only the primary groups of triglycerides. The lipase also exhibited a marked preference for substrates containing endogenously occurring fatty acids and so may prove useful in detailed studies on the physiological relevance of fatty acyl specificity of lipases. The enzyme was not affected by detergents, or thiol-binding agents. Modification of free amino groups caused 90% inhibition, suggesting a role of these groups in the maintenance of lipase activity.
The Importance of Being Tyrosine: Lessons in Molecular Recognition from Minimalist Synthetic Binding Proteins (2009)

Combinatorial libraries built with severely restricted chemical diversity have yielded highly functional synthetic binding proteins. Structural analyses of these minimalist binding sites have revealed the dominant role of large tyrosine residues for mediating molecular contacts and of small serine/glycine residues for providing space and flexibility. The concept of using limited residue types to construct optimized binding proteins mirrors findings in the field of small molecule drug development, where it has been proposed that most drugs are built from a limited set of side chains presented by diverse frameworks. The physicochemical properties of tyrosine make it the amino acid that is most effective for mediating molecular recognition, and protein engineers have taken advantage of these characteristics to build tyrosine-rich protein binding sites that outperform natural proteins in terms of affinity and specificity. Knowledge from preceding studies can be used to improve current designs, and thus synthetic protein libraries will continue to evolve and improve. In the near future, it seems likely that synthetic binding proteins will supersede natural antibodies for most purposes, and moreover, synthetic proteins will enable many new applications beyond the scope of natural proteins.
High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission (1996)

We report the results of a study in previously untreated advanced stage patients with follicular lymphoma (FL) who underwent uniform induction chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) followed by myeloablative therapy and anti-B-cell monoclonal antibody purged autologous bone marrow transplantation (ABMT). Eighty-three patients with previously untreated, low-grade FL were enrolled. After CHOP induction, only 36% achieved complete remission (CR) and 77 patients underwent ABMT. Before BM harvest, 70 patients had a known t(14;18), as determined by polymerase chain reaction (PCR), and all remained PCR positive in the BM at harvest. After ABMT, the disease-free survival (DFS) and overall survival are estimated to be 63% and 89% at 3 years, respectively, with a median follow-up of 45 months. Patients whose BM was PCR negative after purging experienced significantly longer freedom from recurrence (FFR) than those whose BM remained PCR positive (P = .0006). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued CR. This study suggests that a subset of patients with advanced FL may experience prolonged clinical and molecular remissions following high-dose ablative therapy, although longer follow-up will be necessary to determine potential impact on overall survival.
New strategy for the synthesis of oligodeoxynucleotides bearing adducts at exocyclic amino sites of purine nucleosides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew strategy for the synthesis of oligodeoxynucleotides bearing adducts at exocyclic amino sites of purine nucleosidesConstance M. Harris, Liang Zhou, Eric A. Strand, and Thomas M. HarrisCite this: J. Am. Chem. Soc. 1991, 113, 11, 4328–4329Publication Date (Print):May 1, 1991Publication History Published online1 May 2002Published inissue 1 May 1991https://pubs.acs.org/doi/10.1021/ja00011a044https://doi.org/10.1021/ja00011a044research-articleACS PublicationsRequest reuse permissionsArticle Views516Altmetric-Citations89LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Rate of Ovalbumin Messenger Ribonucleic Acid Synthesis in the Oviduct of Estrogen-primed Chicks (1973)

Abstract The concentration of translatable ovalbumin messenger RNA in the tubular gland cells of the chicken oviduct was determined from estimates of relative rate of ovalbumin synthesis, polysome concentration, size of ovalbumin-synthesizing polysomes, DNA concentration, and percentage of tubular gland cells in the oviduct. During secondary stimulation with estrogen, the concentration of ovalbumin messenger RNA rose from undetectable levels to approximately 70,000 molecules per tubular gland cell after 5 days when a steady state was reached. The initial rate of ovalbumin messenger RNA accumulation was about 22 molecules per min per tubular gland cell. Nearly all the translatable ovalbumin messenger RNA was localized in polysomes, even at very early times after hormonal stimulation, suggesting that there is no free pool of untranslated messenger. The half-life of ovalbumin messenger RNA was estimated to be about 24 hours by labeling the RNA in vivo followed by subsequent purification and determination of its specific activity. Two other potential approaches for determining messenger half-life were shown to be unsuitable. Using the half-life value of 24 hours, the steady state rate of ovalbumin messenger RNA synthesis was about 34 molecules per min per tubular gland cell. Based on theoretical values for the maximum rate of messenger RNA transcription in eukaryotes, one ovalbumin gene per haploid genome is sufficient to maintain the observed rate of ovalbumin messenger RNA synthesis.
Characteristics of the hematopoietic stem cell compartment in adult mice (1992)

Mouse hematopoietic stem cells can be enriched from adult bone marrow by a number of methods. The resulting cell populations are heterogeneous in function, suggesting a complex organizational structure within the stem cell compartment. Several assays can be applied to the study of early stages of hematopoiesis; however clonal assays for long-term repopulation, the most critical operational definition of hematopoietic stem cells, are lacking. Further complicating the prospect of understanding early hematopoiesis is the finding that genetic variations among laboratory strains of mice lead to major differences in phenotypic and functional characteristics of hematopoietic stem cells. Application to the human situation of the methodology developed for stem cell isolation and characterization in the mouse will be hampered by the possibility of genetic variations among human subjects and the lack of a well-characterized assay system to detect and quantify cells capable of long-term repopulation of irradiated recipients.
Study of the strata formation during the explosion of a wire in vacuum (2008)

The formation of strata during fast electrical explosions of aluminum wires at current densities of (1–1.4)×108 A/cm2 has been studied experimentally. To observe the strata, the soft x radiation generated at the hot point of an x-pinch was used. It has been revealed that strata are formed before the voltage collapse, that is, at the stage of heating of the wire metal. Two wire explosion modes were realized: with and without cutoff of the current carried by the exploding wire. Analysis of the experimental results shows that the stratification is most probably due to the thermal instability that develops as a consequence of the increase in metal resistivity with temperature.
The renormalization group: Critical phenomena and the Kondo problem (1975)

This review covers several topics involving renormalization group ideas. The solution of the $s$-wave Kondo Hamiltonian, describing a single magnetic impurity in a nonmagnetic metal, is explained in detail. See Secs. VII-IX. "Block spin" methods, applied to the two dimensional Ising model, are explained in Sec. VI. The first three sections give a relatively short review of basic renormalization group ideas, mainly in the context of critical phenomena. The relationship of the modern renormalization group to the older problems of divergences in statistical mechanics and field theory and field theoretic renormalization is discussed in Sec. IV. In Sec. V the special case of "marginal variables" is discussed in detail, along with the relationship of the modern renormalization group to its original formulation by Gell-Mann and Low and others.
A Family History of NIDDM Is Associated With Decreased Aortic Distensibility in Normal Healthy Young Adult Subjects (1996)

A positive family history of NIDDM is associated with decreased aortic distensibility in early adult life. The relevance of these observations to future cardiovascular events merits further investigation.
KRAS gene amplification in colorectal cancer and impact on response to EGFR‐targeted therapy (2013)

KRAS mutations are the most common oncogenic event in colorectal cancer (CRC) progression and their occurrence is associated with lack of response to anti epidermal growth factor receptor (EGFR) targeted therapies. Using preclinical models and patients' samples we recently reported that the emergence of KRAS mutations but also KRAS amplification is associated with acquired resistance to the EGFR inhibitors cetuximab or panitumumab. We reasoned that KRAS amplification may also be responsible for primary resistance to these agents. Furthermore, while the prevalence of KRAS mutations has been well established in CRC, little is known about the frequency of KRAS amplification in large CRC series. We performed a screening of 1,039 CRC samples to assess the prevalence of KRAS amplification in this tumor type and further evaluated the role of this genetic alteration on the sensitivity to anti EGFR therapies. We detected KRAS amplification in 7/1,039 (0.67%) and 1/102 evaluable CRC specimens and cell lines, respectively. KRAS amplification was mutually exclusive with KRAS mutations. Tumors or cell lines harboring this genetic lesion are not responsive to anti-EGFR inhibitors. Although KRAS amplification is an infrequent event in CRC, it might be responsible for precluding response to anti-EGFR treatment in a small proportion of patients.
Depression of B-Lymphocytes by Mastitis and Treatment with Levamisole (1983)

Proportion of B-lymphocytes in milk and blood decreased simultaneously with development of mastitis induced with endotoxin and recovered with disappearance of clinical signs. However, the change in T-lymphocytes was slight. The reduced percentage of B-lymphocytes was caused by reduction in absolute number of such cells. When used orally, levamisole increased the proportion B-lymphocytes of milk to the same as or more than that of similar cells in peripheral blood. This compound may enhance activity of the bovine mammary immune system and be of value for control of bovine mastitis.
Amphipathic DNA Polymers are Candidate Vaginal Microbicides and Block Herpes Simplex Virus Binding, Entry and Viral Gene Expression (2007)

REP 9 and REP 9C represent a novel class of antiviral agents that act by multiple mechanisms. These compounds warrant further development for systemic or topical delivery for the prevention and treatment of HIV and HSV.
Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy (2007)

Nanocurcumin provides an opportunity to expand the clinical repertoire of this efficacious agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin are warranted in pre-clinical in vivo models of cancer and other diseases that might benefit from the effects of curcumin.
<title>Characterization of a full-field digital mammography detector based on direct x-ray conversion in selenium</title> (2002)

We describe a high-resolution digital x-ray detector suitable for producing high quality mammographic images. The detector consists of an array of 3584 by 4096 pixels on 70 micrometer centers covering an area of 25 cm by 29 cm. The conversion layer of the detector is 250 micrometer thick amorphous selenium. Each pixel of the array consists of a storage capacitor for collecting x-ray signals and an amorphous silicon switching transistor. The signal is read out by custom high-speed, low-noise electronics. The integration of this detector with a mammographic x-ray system and acquisition console is described, as well as algorithms for calibration of the full system. We review characterization of the imaging performance of our system based on quantitative analyses of MTF and DQE data, and compare experimental results with theoretical calculations. We compare the performance of our direct conversion system with that of screen/film analog systems and indirect conversion digital detectors, such as LORAD's CsI/CCD detector, operated under similar conditions. MTF degradation mechanisms and system noise sources and their effect on DQE are discussed. We review qualitative aspects of image quality from our detector and present preliminary observer performance characteristics on clinical studies run with our system.
Studies on the presence of magnesium in visceral amyloid. (1994)

The Magneson and Titan yellow tests were used to detect Mg in amyloid deposits in primary and secondary amyloidosis, in a pituitary tumour and in a case of equine cutaneous amyloidosis. Especially vascular amyloid deposits turned out to contain high levels of Mg. The significance of these findings remains unclear at present. Competition between Mg and Ca, the relationship between Mg in elastic fibres and amyloid P-component, and the high water content of amyloid along with the interaction of Mg with water are discussed.
Evaluation of central serotonergic function in affective and related disorders by the fenfluramine challenge test: a critical review (1998)

Plasma prolactin levels following oral administration of the serotonin (5-HT) releasing agent, fenfluramine hydrochloride, have been extensively used to evaluate central serotonergic function in affective and related disorders. Cortisol responses to fenfluramine have generally been a less informative measure. In healthy subjects, prolactin release by fenfluramine is dose-dependent, blocked by antagonists of serotonin receptors of the 5-HT-2a/2c type, negatively correlated with age and increased in young females. In major depression, a preponderance of studies have found blunted prolactin responses compared to matched normal controls. Although a significant minority of studies have not found blunting, increased prolactin release has not been observed. The blunted prolactin release is not due to a deficient secretory capacity of pituitary lactotrophs and is congruent with other evidence for reduced central serotonergic function in major depression. Blunting of the prolactin response may be associated with severity of depression and with elevated baseline cortisol levels. Treatment with antidepressant drugs and electroconvulsive therapy has been reported to increase the prolactin response but this has not been replicated in all studies. Blunted prolactin responses to fenfluramine have been fairly consistently associated with impulsive aggression in different personality disorders and with severity of suicide attempts in depressed patients. A number of studies employing the fenfluramine challenge test (FCT) have been conducted in obsessive compulsive disorder but their results have been variable. Prolactin responses to fenfluramine may be enhanced in panic disorder and chronic fatigue syndrome but the number of studies in these conditions is small as is the case for seasonal affective disorder. Since the therapeutic administration of fenfluramine as an appetite suppressant has been suspended because of reports of cardiac complications, further use of this compound as a challenge agent is not anticipated. Future studies are likely to employ agents acting on specific serotonin receptors and should apply methodological insights from the use of the FCT, which are considered in this review. Use of concomitant brain imaging to evaluate the central effects of challenge agents directly is likely to become more prevalent and may supplant neuroendocrine challenge paradigms such as the FCT which have been remarkably heuristic but are limited in scope and methodologically complex.
Emerging targets in human lymphoma: targeting the MYD88 mutation (2013)

Abstract: B cell neoplasms co-opt the molecular machinery of normal B cells for their survival. Technological advances in cancer genomics has significantly contributed to uncovering the root cause of aggressive lymphomas, revealing a previously unknown link between TLR signaling and B cell neoplasm. Recurrent oncogenic mutations in MYD88 have been found in 39% of the activated B cell-like subtype of diffuse large B cell lymphoma (ABC DLBCL). Interestingly, 29% of ABC DLBCL have a single amino acid substitution of proline for the leucine at position 265 (L265P), and the exact same variant has also been identified in a number of lymphoid malignancies. The MYD88 L265P variant was recently identified in 90% of Wadenstrom's macroglobulinemia patients. These recent developments warrant the need for novel diagnostic tools as well as targeted therapeutics. In this review, we discuss the physiological functions of MYD88 and focus on its role in B cell lymphomas, evaluating the potential for targeting oncogenic MYD88 in lymphoma. Keywords: MYD88, L265P mutation, lymphoma, targeted therapy
Enzymatic Hydrolysis of Wheat Arabinoxylan by a Recombinant “Minimal” Enzyme Cocktail Containing β‐Xylosidase and Novel endo ‐1,4‐β‐Xylanase and α‐ l ‐Arabinofuranosidase Activities (2007)

This study describes the identification of the key enzyme activities required in a "minimal" enzyme cocktail able to catalyze hydrolysis of water-soluble and water-insoluble wheat arabinoxylan and whole vinasse, a fermentation effluent resulting from industrial ethanol manufacture from wheat. The optimal arabinose-releasing and xylan-depolymerizing enzyme activities were identified from data obtained when selected, recombinant enzymes were systematically supplemented to the different arabinoxylan substrates in mixtures; this examination revealed three novel alpha-l-arabinofuranosidase activities: (i) one GH51 enzyme from Meripilus giganteus and (ii) one GH51 enzyme from Humicola insolens, both able to catalyze arabinose release from singly substituted xylose; and (iii) one GH43 enzyme from H. insolens able to catalyze the release of arabinose from doubly substituted xylose. Treatment of water-soluble and water-insoluble wheat arabinoxylan with an enzyme cocktail containing a 20%:20%:20%:40% mixture and a 25%:25%:25%:25% mixture, respectively, of the GH43 alpha-l-arabinofuranosidase from H. insolens (Abf II), the GH51 alpha-l-arabinofuranosidase from M. giganteus (Abf III), a GH10 endo-1,4-beta-xylanase from H. insolens (Xyl III), and a GH3 beta-xylosidase from Trichoderma reesei (beta-xyl) released 322 mg of arabinose and 512 mg of xylose per gram of water-soluble wheat arabinoxylan dry matter and 150 mg of arabinose and 266 mg of xylose per gram of water-insoluble wheat arabinoxylan dry matter after 24 h at pH 5, 50 degrees C. A 10%:40%:50% mixture of Abf II, Abf III, and beta-xyl released 56 mg of arabinose and 91 mg of xylose per gram of vinasse dry matter after 24 h at pH 5, 50 degrees C. The optimal dosages of the "minimal" enzyme cocktails were determined to be 0.4, 0.3, and 0.2 g enzyme protein per kilogram of substrate dry matter for the water-soluble wheat arabinoxylan, the water-insoluble wheat arabinoxylan, and the vinasse, respectively. These enzyme protein dosage levels were approximately 14, approximately 18, and approximately 27 times lower than the dosages used previously, when the same wheat arabinoxylan substrates were hydrolyzed with a combination of Ultraflo L and Celluclast 1.5 L, two commercially available enzyme preparations produced by H. insolens and T. reesei.
The Unanticipated Difficult Intubation in Obstetrics (2011)

In this focused review, we discuss an algorithm specifically for the unanticipated difficult intubation in obstetrics. This generic algorithm emphasizes a standardized and prespecified sequence of interventions to provide safe, efficient, and effective airway management for the emergency obstetric surgical patient. Individual institutions and anesthesia providers are encouraged to use this framework to select specific pieces of equipment for each step, and to create regular opportunities for all obstetric anesthesia providers to become facile with each airway device and to integrate the algorithm under simulated conditions.