gebhart/patrepeval huggingface dataset:
Carbohydrate Structures of Human Tissue Plasminogen Activator Expressed in Chinese Hamster Ovary Cells (1989)

Recombinant human tissue plasminogen activator (rt-PA), produced by expression in Chinese hamster ovary cells, is a fibrin-specific plasminogen activator which has been approved for clinical use in the treatment of myocardial infarction. In this study, the structures of the Asn-linked oligosaccharides of Chinese hamster ovary-expressed rt-PA have been elucidated. High mannose and hybrid oligosaccharides were released from the protein by endoglycosidase H digestion, whereas N-acetyllactosamine-type ("complex") oligosaccharides were released by peptide:N-glycosidase F digestion. The oligosaccharides were fractionated by gel permeation chromatography and anion exchange high performance liquid chromatography (HPLC), and their structures were analyzed by composition and methylation analysis, high pH anion exchange chromatography, fast atom bombardment-mass spectrometry (FAB-MS), and 500-MHz 1H NMR spectroscopy. High mannose oligosaccharides were found to account for 38% of the total carbohydrate content of rt-PA and consisted of Man5GlcNAc2, Man6GlcNAc2, and Man7GlcNAc2 in the ratio 1.8:1.7:1. Two hybrid oligosaccharides were identified and accounted for 3% of the carbohydrate of rt-PA. The N-acetyllactosamine-type oligosaccharides were found to comprise diantennary (34% of total carbohydrate), 2,4-branched triantennary (11%), 2,6-branched triantennary (9%), and tetraantennary (5%) structures. Sialylation of these oligosaccharides was by alpha (2----3) linkages to galactose. Most (greater than 90%) of the N-acetyllactosamine-type structures contained fucose alpha (1----6) linked to the Asn-linked N-acetylglucosamine residue. The distribution of oligosaccharide structures at individual glycosylation sites (Asn residues 117, 184, and 448) was also determined. rt-PA exists as two variants that differ by the presence (type I) or absence (type II) of carbohydrate at Asn-184. Tryptic glycopeptides were isolated by reversed phase high performance liquid chromatography and treated with peptide:N-glycosidase F. The oligosaccharides released from each glycosylation site were analyzed by high pH anion exchange chromatography. By this analysis, Asn-117 was demonstrated to carry exclusively high mannose oligosaccharides. When glycosylated, Asn-184 carried diantennary, 2,4-branched triantennary, 2,6-branched triantennary, and tetraantennary N- acetyllactosamine oligosaccharides in the ratio 9.0:4.5:1.4:1. Asn- 448 carried the same types of oligosaccharides, but in the ratio 7.5:1.6:2.1:1. The distributions of Asn-linked oligosaccharides at positions 117 and 448 were found not to be affected by the presence or absence of carbohydrate at position 184. The relevance of the
The endothelium: a new target for therapy (2000)

At one time considered merely a monolayer of cells lining the vascular conduit, the endothelium has emerged recently as an organ with functions as complex as any in the body. A highly active regulatory organ, the endothelium senses and assesses the hemodynamic, humoral, and inflammatory signals to which it is constantly exposed by the blood and responds by secreting factors that affect vessel tone and structure. These interactions are not merely of academic interest. It has been increasingly recognized that endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis and coronary artery disease.
Screening for Adenylosuccinate Lyase Deficiency: Clinical, Biochemical and Molecular Findings in Four Patients (2002)

Adenylosuccinate lyase deficiency is an autosomal recessive defect of purine metabolism. Succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr) are the disease marker metabolites in physiological fluids. The Bratton-Marshall test for detection of SAICAr in urine has been added to the selective screening for inborn errors of metabolism that is carried out in our lab. During the last three years, around 2,000 patients have been screened by this method, resulting in the detection of four new cases with this disease. They all presented with severe psychomotor delay, hypotonia and refractory epilepsy since the neonatal period. The S-Ado/SAICAr ratio in cerebrospinal fluid was below 2, indicating that they correspond to the most severe form of the disease. New missense mutations were found in a heterozygous fashion in three patients. The study of purines in all patients with neurological disease of unknown etiology is highly recommended.
N′-Substituted-2′-O,3′-N-carbonimidoyl Bridged Macrolides: Novel Anti-inflammatory Macrolides without Antimicrobial Activity (2012)

Macrolide antibiotics, like erythromycin, clarithromycin, and azithromycin, possess anti-inflammatory properties. These properties are considered fundamental to the efficacy of these three macrolides in the treatment of chronic inflammatory diseases like diffuse panbronchiolitis and cystic fibrosis. However, long-term treatment with macrolide antibiotics presents a considerable risk for promotion of bacterial resistance. We have examined antibacterial and anti-inflammatory effects of a novel macrolide class: N'-substituted 2'-O,3'-N-carbonimidoyl bridged erythromycin-derived 14- and 15-membered macrolides. A small focused library was prepared, and compounds without antimicrobial activity, which inhibited IL-6 production, were selected. Data analysis led to a statistical model that could be used for the design of novel anti-inflammatory macrolides. The most promising compound from this library retained the anti-inflammatory activity observed with azithromycin in lipopolysaccharide-induced pulmonary neutrophilia in vivo. Importantly, this study strongly suggests that antimicrobial and anti-inflammatory activities of macrolides are independent and can be separated, which raises development plausibility of novel anti-inflammatory therapeutics.
Integrated chemical systems: photocatalysis at titanium dioxide incorporated into Nafion and clay (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntegrated chemical systems: photocatalysis at titanium dioxide incorporated into Nafion and clayFu Ren F. Fan, Hsue Yang Liu, and Allen J. BardCite this: J. Phys. Chem. 1985, 89, 21, 4418–4420Publication Date (Print):October 1, 1985Publication History Published online1 May 2002Published inissue 1 October 1985https://pubs.acs.org/doi/10.1021/j100267a003https://doi.org/10.1021/j100267a003research-articleACS PublicationsRequest reuse permissionsArticle Views282Altmetric-Citations60LEARN 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 options Get e-Alerts
Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer (2009)

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2-6.0; P=0.01). Analyses of approximately 1000 stage I-III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC.
Patterns of three-dimensional growth in vitro in collagen-coated cellulose sponge: carcinomas and embryonic tissues. (1968)

Summary Several transplantable tumors and chick embryonic tissues were cultured in collagen-coated cellulose sponge. The growth obtained in this matrix was compared with that obtained in cellulose sponge alone and in collagen sponge alone. The tumors included a mouse mammary adenocarcinoma (C3HBA), a squamous cell carcinoma of the mouse cervix (D-98), a mouse ascites hepatoma (Sato A H #134), a rat ascites hepatoma (Yoshida #7974), and a human adenocarcinoma of the colon (H.Ad.-1). The embryonic tissues were intestine, lung, and heart. All the sponges were examined in histologic section. The best patterns of migratory outgrowth were seen in collagen-coated cellulose sponge. Conventional histologic criteria were used to identify the cellular components of the newly formed tissues.
Primate motor cortex and free arm movements to visual targets in three- dimensional space. I. Relations between single cell discharge and direction of movement (1988)

We describe the relations between the neuronal activity in primate motor cortex and the direction of arm movement in three-dimensional (3-D) space. The electrical signs of discharge of 568 cells were recorded while monkeys made movements of equal amplitude from the same starting position to 8 visual targets in a reaction time task. The layout of the targets in 3-D space was such that the direction of the movement ranged over the whole 3-D directional continuum in approximately equal angular intervals. We found that the discharge rate of 475/568 (83.6%) cells varied in an orderly fashion with the direction of movement: discharge rate was highest with movements in a certain direction (the cell's "preferred direction") and decreased progressively with movements in other directions, as a function of the cosine of the angle formed by the direction of the movement and the cell's preferred direction. The preferred directions of different cells were distributed throughout 3-D space. These findings generalize to 3-D space previous results obtained in 2-D space (Georgopoulos et al., 1982) and suggest that the motor cortex is a nodal point in the construction of patterns of output signals specifying the direction of arm movement in extrapersonal space.
Early relapse after rituximab chemoimmunotherapy (2007)

In relapsed/refractory childhood acute lymphoblastic leukemia (ALL) of the B-cell lineage rituximab, a monoclonal anti-CD20 antibody was used successfully in some cases. We report on a 15-year-old female with relapsed CD20-positive B-cell progenitor ALL treated with rituximab because of positive minimal residual disease signals after chemotherapy, as checked by flow cytometry and real time quantitative-PCR. Rituximab eliminated the CD20-positive subpopulation, but not the more immature leukemic cells. The patient died with fulminant aspergillosis before hematopoietic stem cell transplantation could be performed.
Light-trap catches of moths within and above the canopy of a northeastern forest (1996)

(Uploaded by Plazi from the Biodiversity Heritage Library) No abstract provided.
FMRI: Use in Early Alzheimer‘s Disease and in Clinical Trials (2008)

The pathophysiological process of Alzheimer’s disease (AD) begins years, even decades, prior to the time a clinical diagnosis can be established. This long asymptomatic or minimally symptomatic phase of AD provides a potential period for early therapeutic interventions to slow and perhaps ultimately prevent the progression to clinical dementia. Functional MRI (fMRI) provides an in vivo means to investigate alterations in brain function related to the earliest symptoms of AD, possibly before development of significant irreversible structural damage. fMRI during tasks probing episodic memory, which is the cognitive function most characteristically impaired in early AD, are of particular interest. In this paper, we review the current knowledge of the pathophysiological fMRI correlates of AD and of at-risk states for AD, such as presence of mild cognitive impairment or the apolipoprotein E ε4 allele. We will summarize previous studies demonstrating changes in task-related fMRI activity, primarily focusing on memory tasks, as well as studies investigating resting-state fMRI findings in clinical AD patients and at-risk subjects compared with healthy elderly individuals. We will also discuss the potential use of fMRI in clinical trials of AD therapeutic agents, as well as the limitations of this promising imaging technique.
Complement System in Lung Disease (2014)

In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions.
Vertical leaping mechanics of the Lesser Egyptian Jerboa reveal specialization for maneuverability rather than elastic energy storage (2017)

The limited use of tendon elastic energy storage in the jerboa parallels the morphologically similar heteromyid kangaroo rat, <i>Dipodomys spectabilis</i>. When compared to larger saltatory kangaroos and wallabies that sustain hopping over longer periods of time, these small saltatory rodents store and recover less elastic strain energy in their tendons. The large contribution of muscle work, rather than elastic strain energy, to the vertical leap suggests that the fitness benefit of rapid acceleration for predator avoidance dominated over the need to enhance locomotor economy in the evolutionary history of jerboas.
The molecular basis of lung cancer: molecular abnormalities and therapeutic implications (2003)

Lung cancer is the number one cause of cancer-related death in the western world. Its incidence is highly correlated with cigarette smoking, and about 10% of long-term smokers will eventually be diagnosed with lung cancer, underscoring the need for strengthened anti-tobacco policies. Among the 10% of patients who develop lung cancer without a smoking history, the environmental or inherited causes of lung cancer are usually unclear. There is no validated screening method for lung cancer even in high-risk populations and the overall five-year survival has not changed significantly in the last 20 years. However, major progress has been made in the understanding of the disease and we are beginning to see this knowledge translated into the clinic. In this review, we will summarize the current state of knowledge regarding the cascade of events associated with lung cancer development. From subclinical DNA damage to overt invasive disease, the mechanisms leading to clinically and molecularly heterogeneous tumors are being unraveled. These lesions allow cells to escape the normal regulation of cell division, apoptosis and invasion. While all subtypes of non-small cell lung cancer have historically been treated the same, stage-for-stage, recent technological advances have allowed a better understanding of the molecular classification of the disease and provide hypotheses for molecular early detection and targeted therapeutic strategies.
Deep-ultraviolet lasing at 243 nm from photo-pumped AlGaN/AlN heterostructure on AlN substrate (2013)

Deep-ultraviolet lasing was achieved at 243.5 nm from an AlxGa1−xN-based multi-quantum-well structure using a pulsed excimer laser for optical pumping. The threshold pump power density at room-temperature was 427 kW/cm2 with transverse electric (TE)-polarization-dominant emission. The structure was epitaxially grown by metalorganic chemical vapor deposition on an Al-polar free-standing AlN (0001) substrate. Stimulated emission is achieved by design of the active region, optimizing the growth, and the reduction in defect density afforded by homoepitaxial growth of AlN buffer layers on AlN substrates, demonstrating the feasibility of deep-ultraviolet diode lasers on free-standing AlN.
Mouse model for Chagas disease: immunohistochemical distribution of different stages of Trypanosoma cruzi in tissues throughout infection. (2001)

Different stages of Trypanosoma cruzi are seen during mammalian infection. Histologic sections of infected hearts have shown amastigotes and, when using immunohistochemistry (IHC), parasite antigens; however, demonstration of trypomastigotes in these tissues has proven elusive. Using a mouse strain that develops chagasic cardiomyopathy (histologically similar to human infection) 70 days after injecting T. cruzi-Brazil strain, we studied the distribution of parasite stages and the extent of inflammation. All organs had varying amounts of mononuclear inflammation by day 10, which peaked between day 20 and day 30, and decreased by day 50. Amastigotes were detected in myocytes, histiocytes, acinar pancreatic cells, astrocytes and ependymal cells by day 10, and the number of amastigotes peaked on day 30. Immunohistochemistry demonstrated trypomastigotes in sinusoids, vessels and interstitial tissues of several organs between day 15 and 50. Abundant parasite antigens (granular staining) were detected in connective tissues throughout the infection. The burden of amastigotes and trypomastigotes during the acute phase seems to correlate with the degree of inflammation and granular staining in the chronic stage.
alpha-difluoromethylornithine induces apoptosis as well as anti-angiogenesis in the inhibition of tumor growth and metastasis in a human gastric cancer model. (2000)

Polyamines are essential in various biological systems such as cellular proliferation including tumor growth, differentiation and neoplastic transformation including carcinogenesis. alpha-Difluoromethylornithine (DFMO) is a specific irreversible inhibitor of ornithine decarboxylase, a key enzyme in polyamine biosynthesis, and has been used for clinical chemotherapy and chemoprevention trials against several tumors with various effects. The cellular mechanisms of DFMO action are unclear. Because our hypothesis with regard to polyamine-directed chemoprevention includes anti-angiogenesis and apoptosis as essential parts of the cellular mechanism of action of DFMO, we examined these effects in our human gastric cancer model. In our initial experiments, DFMO inhibited the growth of both human umbilical vein endothelial cells (HUVEC), angio-endothelial cells in vitro, and KKLS, a gastric cancer cell line, in culture, and also the growth of KKLS cells transplanted into nude mice. DFMO also inhibited liver metastasis of KKLS orthotransplanted in the stomach of nude mice. The vessel density of DFMO-treated tumors was significantly lower than that of non-treated tumors. The apoptotic index was significantly greater in DFMO-treated tumors than in non-treated tumors. These results suggest that anti-angiogenesis and apoptosis play significant roles in the DFMO inhibition of the growth and metastasis in this human gastric cancer model and provide evidence that DFMO induces apoptosis.
Vertebrate Sprouty genes are induced by FGF signaling and can cause chondrodysplasia when overexpressed (1999)

The Drosophila sprouty gene encodes an antagonist of FGF and EGF signaling whose expression is induced by the signaling pathways that it inhibits. Here we describe a family of vertebrate Sprouty homologs and demonstrate that the regulatory relationship with FGF pathways has been conserved. In both mouse and chick embryos, Sprouty genes are expressed in intimate association with FGF signaling centers. Gain- and loss-of-function experiments demonstrate that FGF signaling induces Sprouty gene expression in various tissues. Sprouty overexpression obtained by infecting the prospective wing territory of the chick embryo with a retrovirus containing a mouse Sprouty gene causes a reduction in limb bud outgrowth and other effects consistent with reduced FGF signaling from the apical ectodermal ridge. At later stages of development in the infected limbs there was a dramatic reduction in skeletal element length due to an inhibition of chondrocyte differentiation. The results provide evidence that vertebrate Sprouty proteins function as FGF-induced feedback inhibitors, and suggest a possible role for Sprouty genes in the pathogenesis of specific human chondrodysplasias caused by activating mutations in Fgfr3.
Antibacterial Effect of Human Mesenchymal Stem Cells Is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37 (2010)

Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E. coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/ LL-37.