gebhart/patrepeval huggingface dataset:
Catalog-Library Approach for the Rapid and Sensitive Structural Elucidation of Oligosaccharides (1999)

We obtained the nearly complete structural elucidation of oligosaccharide components, including sequence, linkage, and even stereochemistry in the picomolar levels. The "catalog-library" approach is used for elucidating the structures of minor components in a mixture of oligosaccharides. Oligosaccharides released from a family of glycoproteins are often composed of a small finite set of monosaccharides. In this regard, the numerous oligosaccharide species are analogous to the products found in syntheses involving combinatorial libraries. The great structural diversity in the library is the result of the nearly infinite combinations in which even a small number of monosaccharides can be arranged. Fortunately, structural similarities exist between different oligosaccharides, as specific substructural motifs are preserved among different compounds. We propose that a catalog of substructural motifs can be identified and characterized by collision-induced dissociation mass spectrometry. The catalog is constructed from a set of known compounds that have been fully structurally elucidated by, for example, nuclear magnetic resonance. The catalog consists of the characteristic fragmentation patterns belonging to a set of specific substructural motifs. Collision-induced dissociation is used to determine the presence of these motifs and reconstruct the structures of less abundant components.
ErbB receptors: from oncogenes to targeted cancer therapies (2007)

Understanding the genetic origin of cancer at the molecular level has facilitated the development of novel targeted therapies. Aberrant activation of the ErbB family of receptors is implicated in many human cancers and is already the target of several anticancer therapeutics. The use of mAbs specific for the extracellular domain of ErbB receptors was the first implementation of rational targeted therapy. The cytoplasmic tyrosine kinase domain is also a preferred target for small compounds that inhibit the kinase activity of these receptors. However, current therapy has not yet been optimized, allowing for opportunities for optimization of the next generation of targeted therapy, particularly with regards to inhibiting heteromeric ErbB family receptor complexes.
Stability of nizatidine in extemporaneous oral liquid preparations (1990)

The stability of nizatidine in extemporaneous oral liquid preparations stored at room and refrigerated temperatures was studied. Preparations containing nizatidine in a final concentration of approximately 2.5 mg/mL were made by mixing the contents of a 300-mg nizatidine capsule with commercial juices (Gatorade, Stokely-Van Camp; Cran-Grape, Ocean Spray; apple juice, Sundor Brands; and V8 vegetable juice, Campbell Soup) and with aluminum hydroxide-magnesium hydroxide suspension (Maalox, Rorer). A control solution was prepared in water. Samples of each preparation were stored at 15-30°C and at 5°C. Initially and after 4, 8, 24, and 48 hours of storage, the samples were visually inspected, tested for pH, and analyzed in triplicate by high-performance liquid chromatography for nizatidine content. No appreciable changes in appearance or pH occurred. The only extemporaneous preparations with greater than 10% loss of nizatidine potency at 48 hours were the Cran-Grape and V8 preparations at room temperature. There was no correlation between pH of the preparations and changes in drug concentration. In the Maalox and V8 preparations, the drug powder did not dissolve uniformly. In all the preparations tested, nizatidine was stable for at least eight hours at refrigerated and room temperatures. In all except the Cran-Grape and V8 preparations, the drug was stable for 48 hours under both storage conditions.
Organoboron Compounds. II. Preparation and Properties of Some Trialkylboroxines1—3 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganoboron Compounds. II. Preparation and Properties of Some Trialkylboroxines1—3Patrick A. McCusker, Eugene C. Ashby, and Henry S. MakowskiCite this: J. Am. Chem. Soc. 1957, 79, 19, 5179–5181Publication Date (Print):October 1, 1957Publication History Published online1 May 2002Published inissue 1 October 1957https://pubs.acs.org/doi/10.1021/ja01576a026https://doi.org/10.1021/ja01576a026research-articleACS PublicationsRequest reuse permissionsArticle Views916Altmetric-Citations27LEARN 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-Alertsclose Get e-Alerts
MCP-1-mediated chemotaxis requires activation of non-overlapping signal transduction pathways (1997)

Monocyte chemoattractant protein-1 (MCP-1) is a CC chemokine that attracts monocytes and T lymphocytes. Its receptor (CCR2) is a heptahelical G-protein-coupled receptor (GPCR) whose signal transduction pathways for chemotaxis have not been completely defined. Because other GPCRs stimulate the mitogen-activated protein kinase (MAPK) cascade, we examined this pathway's activity in response to MCP-1. MCP-1 induced rapid and transient activation of MAPK in human monocytes and in Chinese hamster ovary cells expressing CCR2B. This effect was largely insensitive to pertussis toxin and wortmannin, and was protein kinase C-dependent and protein tyrosine kinase-independent. PD 098059, an inhibitor of MEK activation, not only prevented MAPK activation but also inhibited MCP-1-induced chemotaxis. Because pertussis toxin and wortmannin also efficiently inhibit chemotaxis but do not completely inhibit MAPK activation, these data may define non-overlapping signal transduction pathways that all must be activated to produce chemokine-mediated chemotaxis.
Mitochondrial transcription factor A regulates mtDNA copy number in mammals (2004)

Mitochondrial DNA (mtDNA) copy number regulation is altered in several human mtDNA-mutation diseases and it is also important in a variety of normal physiological processes. Mitochondrial transcription factor A (TFAM) is essential for human mtDNA transcription and we demonstrate here that it is also a key regulator of mtDNA copy number. We initially performed in vitro transcription studies and determined that the human TFAM protein is a poor activator of mouse mtDNA transcription, despite its high capacity for unspecific DNA binding. Next, we generated P1 artificial chromosome (PAC) transgenic mice ubiquitously expressing human TFAM. The introduced human TFAM gene was regulated in a similar fashion as the endogenous mouse Tfam gene and expression of the human TFAM protein in the mouse did not result in down-regulation of the endogenous expression. The PAC-TFAM mice thus had a net overexpression of TFAM protein and this resulted in a general increase of mtDNA copy number. We used a combination of mice with TFAM overexpression and TFAM knockout and demonstrated that mtDNA copy number is directly proportional to the total TFAM protein levels also in mouse embryos. Interestingly, the expression of human TFAM in the mouse results in up-regulation of mtDNA copy number without increasing respiratory chain capacity or mitochondrial mass. It is thus possible to experimentally dissociate mtDNA copy number regulation from mtDNA expression and mitochondrial biogenesis in mammals in vivo. In conclusion, our results provide genetic evidence for a novel role for TFAM in direct regulation of mtDNA copy number in mammals.
Solvent/detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma (1992)

Fresh frozen plasma (FFP) is prepared in blood banks world-wide as a by-product of red blood cell concentrate preparation. Appropriate clinical use is for coagulation factor disorders where appropriate concentrates are unavailable and when multiple coagulation factor deficits occur such as in surgery. Viral safety depends on donor selection and screening; thus, there continues to be a small but defined risk of viral transmission comparable with that exhibited by whole blood. We have prepared a virus sterilized FFP (S/D-FFP) by treatment of FFP with 1% tri(n-butyl)phosphate (TNBP) and 1% Triton X-100 at 30 degrees C for 4 hours. Added reagents are removed by extraction with soybean oil and chromatography on insolubilized C18 resin. Treatment results in the rapid and complete inactivation of greater than or equal to 10(7.5) infectious doses (ID50) of vesicular stomatitis virus (VSV) and greater than or equal to 10(6.9) ID50 of sindbis virus (used as marker viruses), greater than or equal to 10(6.2) ID50 of human immunodeficiency virus (HIV), greater than or equal to 10(6) chimp infectious doses (CID50) of hepatitis B virus (HBV), and greater than or equal to 10(5) CID50 of hepatitis C virus (HCV). Immunization of rabbits with S/D-FFP and subsequent adsorption of elicited antibodies with untreated FFP confirmed the absence of neoimmungen formation. Coagulation factor content was comparable with that found in FFP. Based on these laboratory and animal studies, together with the extensive history of the successful use of S/D-treated coagulation factor concentrates, we conclude that replacement of FFP with S/D-FFP, prepared in a manufacturing facility, will result in improved virus safety and product uniformity with no loss of efficacy.
On using numerical algebraic geometry to find Lyapunov functions of polynomial dynamical systems (2010)

Lyapunov functions are useful in analyzing the phase plane of dynamical systems. In this paper, we explore the use of techniques from numerical algebraic geometry to find a Lyapunov function of a polynomial dynamical system with a stable fixed point at the origin.
Airway wall remodelling: the influence of corticosteroids (2005)

Further longitudinal interventional studies are required, with multiple airway sampling times, to fully elucidate the full potential for corticosteroids to benefit remodelling of the airways in chronic inflammatory diseases. There needs to be more attention to pathophysiological and clinical correlations in such studies. It is likely that even when used optimally corticosteroids will have limited efficacy overall in this aspect of asthma pathogenesis. The search is on for newer and better treatments.
Role of interleukin-22 in inflammatory bowel disease (2014)

Inflammatory bowel disease (IBD) is a chronic inflammatory disease thought to be mediated by the microbiota of the intestinal lumen and inappropriate immune responses. Aberrant immune responses can cause secretion of harmful cytokines that destroy the epithelium of the gastrointestinal tract, leading to further inflammation. Interleukin (IL)-22 is a member of the IL-10 family of cytokines that was recently discovered to be mainly produced by both adaptive and innate immune cells. Several cytokines and many of the transcriptional factors and T regulatory cells are known to regulate IL-22 expression through activation of signal transducer and activator of transcription 3 signaling cascades. This cytokine induces antimicrobial molecules and proliferative and antiapoptotic pathways, which help prevent tissue damage and aid in its repair. All of these processes play a beneficial role in IBD by enhancing intestinal barrier integrity and epithelial innate immunity. In this review, we discuss recent progress in the involvement of IL-22 in the pathogenesis of IBD, as well as its therapeutic potential.
Does early nutrition in infants born before term programme later blood pressure? (1994)

Extremes of nutritional intake and growth performance in preterm infants do not programme later blood pressure at 7.5-8 years of age. These findings do not support the hypothesis that high blood pressure has early nutritional origins. We suggest that the long term rise in blood pressure reported in individuals who had low birthweight (at full term) is not, as previously speculated, due to poor fetal nutrition or growth as such.
Generation of Induced Pluripotent Stem Cells by Efficient Reprogramming of Adult Bone Marrow Cells (2009)

Reprogramming of somatic cells provides potential for the generation of specific cell types, which could be a key step in the study and treatment of human diseases. In vitro reprogramming of somatic cells into a pluripotent embryonic stem (ES) cell-like state has been reported by retroviral transduction of murine fibroblasts using four embryonic transcription factors or through cell fusion of somatic and pluripotent stem cells. Here we show that mouse adult bone marrow mononuclear cells (BM MNCs) are competent as donor cells and can be reprogrammed into pluripotent ES cell-like cells. We isolated BM MNCs and mouse embryonic fibroblasts (MEFs) from Oct4-GFP transgenic mice, fused them with ES cells, or infected them with retroviruses expressing Oct4, Sox2, Klf4, and c-Myc. Fused BM MNCs formed more ES-like colonies than did MEFs. Infected BM MNCs gave rise to induced pluripotent stem (iPS) cells, although transduction efficiencies were not high. It was more efficient to pick up iPS colonies as compared with MEFs. BM-derived iPS (BM iPS) cells expressed ES cell markers, formed teratomas, and contributed to chimera mice with germ line development. Clonal analysis revealed that BM iPS clones had diversity, although some clones were found to be genetically identical with different phenotypes. Our findings imply that BM MNCs have potential advantages to generate iPS cells for the clinical application.
Infusion of Human Umbilical Cord Blood Cells in a Rat Model of Stroke Dose-Dependently Rescues Behavioral Deficits and Reduces Infarct Volume (2004)

These results extend previous observations of HUCBC infusion in the MCAO rat stroke model by demonstrating a dose relationship between HUCBC, behavioral improvement, and neuronal sparing.
Correction of β-thalassemia mutant by base editor in human embryos (2017)

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
Neurodegeneration (2004)

This chapter contains sections titled: What Is Neuroprotection? Outcome Measures in Clinical Studies Specific Diseases Wilson's Disease Parkinson's Disease DATATOP Study Dopamine Agonists Anti-Excitotoxic Treatment Neurotrophins MAP Kinase Inhibitors Transplantation Deep Brain Stimulation Coenzyme Q10 Multiple System Atrophy and Progressive Supranuclear Palsy Alzheimer's Disease Symptomatic Treatment Antioxidants Anti-inflammatory Approaches Estrogen Replacement NMDA Receptor Antagonists Experimental Therapies Immunization Cholesterol-lowering Therapy Huntington's Disease Why Do So Many Clinical Studies Fail? What Do We Need? References
Electrospun Collagen: A Tissue Engineering Scaffold with Unique Functional Properties in a Wide Variety of Applications (2011)

Type I collagen and gelatin, a derivative of Type I collagen that has been denatured, can each be electrospun into tissue engineering scaffolds composed of nano- to micron-scale diameter fibers. We characterize the biological activity of these materials in a variety of tissue engineering applications, including endothelial cell-scaffold interactions, the onset of bone mineralization, dermal reconstruction, and the fabrication of skeletal muscle prosthetics. Electrospun collgen (esC) consistently exhibited unique biological properties in these functional assays. Even though gelatin can be spun into fibrillar scaffolds that resemble scaffolds of esC, our assays reveal that electrospun gelatin (esG) lacks intact α chains and is composed of proinflammatory peptide fragments. In contrast, esC retains intact α chains and is enriched in the α 2(I) subunit. The distinct fundamental properties of the constituent subunits that make up esC and esG appear to define their biological and functional properties.
Hyaluronan, CD44 and versican in epidermal keratinocyte tumours (2003)

The completely different hyaluronan and CD44 expression patterns in BCC and SCC probably reflect the different origins of the tumours, with BCC an undifferentiated keratinocyte and SCC a keratinocyte at an early stage in the differentiation pathway. The difference in hyaluronan and CD44 expression between these tumours may also contribute to the difference in their capacity to metastasize.
PREVENTION OF TYPE 2 DIABETES (1998)

Type 2 diabetes is a major cause of morbidity and mortality resulting from its microangiopathic and macroangiopathic complications. Current approaches to its management and to the prevention of diabetic complications are difficult to implement effectively, and there is little evidence to date that these approaches are reducing the impact of this disease. The recognition that type 2 diabetes usually has a prolonged prediabetic phase raises the possibility that the emergence of hyperglycemia and the atherosclerotic complications associated with diabetes may be preventable by the institution of early treatment modalities. Sufficient data suggest that life-style modification or pharmacotherapy directed at improving insulin sensitivity or insulin secretion in subjects with impaired glucose tolerance may reduce progression to diabetes. Two long-term prospective, controlled trials have been initiated to test this hypothesis.
Recommendations for the Establishment of Primary Stroke Centers (2000)

Randomized clinical trials and observational studies suggest that several elements of a stroke center would improve patient care and outcomes. Key elements of primary stroke centers include acute stroke teams, stroke units, written care protocols, and an integrated emergency response system. Important support services include availability and interpretation of computed tomography scans 24 hours everyday and rapid laboratory testing. Administrative support, strong leadership, and continuing education are also important elements for stroke centers. Adoption of these recommendations may increase the use of appropriate diagnostic and therapeutic modalities and reduce peristroke complications. The establishment of primary stroke centers has the potential to improve the care of patients with stroke. JAMA. 2000.
Deposition and Characterization of Extended Single-Stranded DNA Molecules on Surfaces (2001)

We have devised an approach for generating well-extended, surface deposited, single-stranded DNA molecules having minimal intramolecular base-pairing. This method depends on careful control of the mica surface charge, appropriate selection of the ionic strength of the DNA solution, and controlled translation of a droplet of DNA solution along the surface. We have shown the general applicability of this technique by elongating ΦX174, M13mp18, and λ single-stranded DNA on mica followed by imaging with atomic force microscopy. We have further demonstrated the feasibility of more elaborate, multistep surface preparations by aligning λ double-stranded DNA and ΦX174 single-stranded DNA in orthogonal directions on the same substrate.
Towards a ‘Human‐like’ Model of Tuberculosis: Intranasal Inoculation of LPS Induces Intragranulomatous Lung Necrosis in Mice Infected Aerogenically with Mycobacterium tuberculosis (2001)

It is well known that one of the differences between murine and human tuberculosis is the lack of intragranulomatous necrosis in the former. The aim of this study was to create a feasible and reproducible model of an experimental model of murine tuberculosis in which this necrosis should be present. Considering the Shwartzman reaction as a possible explanation for intragranulomatous necrosis in human tuberculosis, C57Bl/6 mice, infected aerogenically with a virulent strain of Mycobacterium tuberculosis, were intranasally inoculated with lipopolysaccharide (LPS) on day 19 postinfection (p.i.). Twenty-four hours later, neutrophils infiltrated the lung parenchyma in a significant level, and 10 days after necrosis could be detected in the centres of primary granulomas, that showed scanty macrophages and large amounts of collagen on an eosinophilic background. On the other hand, a significant decrease in the concentration of colony forming units (CFU) could be appreciated 24 h after the LPS inoculation. Afterwards, nonbronchogenic spreading of granulomas increased and higher levels of interferon (IFN)-gamma mRNA were detected. These results lend support to the Shwartzman reaction as the origin of the intragranulomatous necrosis in the M. tuberculosis infection, and provides a useful tool to improve experimental murine models in tuberculosis.