gebhart/patrepeval huggingface dataset:
Chemical Topology: Complex Molecular Knots, Links, and Entanglements (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTChemical Topology: Complex Molecular Knots, Links, and EntanglementsRoss S. Forgan, Jean-Pierre Sauvage*, and J. Fraser Stoddart*View Author Information Center for the Chemistry of Integrated Systems and the Department of Chemistry, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, United StatesFax: (847) 491-1009. E-mail: [email protected] (J.-P.S.); [email protected] (J.F.S.).Cite this: Chem. Rev. 2011, 111, 9, 5434–5464Publication Date (Web):June 21, 2011Publication History Received24 January 2011Published online21 June 2011Published inissue 14 September 2011https://pubs.acs.org/doi/10.1021/cr200034uhttps://doi.org/10.1021/cr200034ureview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views14058Altmetric-Citations733LEARN 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 SUBJECTS:Genetics,Ligands,Macrocycles,Mathematical methods,Molecular structure Get e-Alerts
Parametric and nonparametric linkage analysis: a unified multipoint approach. (1996)

In complex disease studies, it is crucial to perform multipoint linkage analysis with many markers and to use robust nonparametric methods that take account of all pedigree information. Currently available methods fall short in both regards. In this paper, we describe how to extract complete multipoint inheritance information from general pedigrees of moderate size. This information is captured in the multipoint inheritance distribution, which provides a framework for a unified approach to both parametric and nonparametric methods of linkage analysis. Specifically, the approach includes the following: (1) Rapid exact computation of multipoint LOD scores involving dozens of highly polymorphic markers, even in the presence of loops and missing data. (2) Non-parametric linkage (NPL) analysis, a powerful new approach to pedigree analysis. We show that NPL is robust to uncertainty about mode of inheritance, is much more powerful than commonly used nonparametric methods, and loses little power relative to parametric linkage analysis. NPL thus appears to be the method of choice for pedigree studies of complex traits. (3) Information-content mapping, which measures the fraction of the total inheritance information extracted by the available marker data and points out the regions in which typing additional markers is most useful. (4) Maximum-likelihood reconstruction of many-marker haplotypes, even in pedigrees with missing data. We have implemented NPL analysis, LOD-score computation, information-content mapping, and haplotype reconstruction in a new computer package, GENEHUNTER. The package allows efficient multipoint analysis of pedigree data to be performed rapidly in a single user-friendly environment.
The minipig as an alternative non-rodent model for immunogenicity testing using the TNFα blockers adalimumab and infliximab (2013)

Immunogenicity is a major issue of concern for monoclonal antibodies used in human diseases and is by default mainly determined in non-human primates (NHP), as target molecules are considered most similar in NHP compared to human. In this manuscript the predictive value of immunogenicity testing in minipigs for human safety is evaluated, as the immune system of the pig is functionally similar to that in other mammalian species. Adalimumab and infliximab (both monoclonal antibodies blocking TNFα) were used as model substances. Female Göttingen minipigs (4/group) were treated every other week with low (0.1 mg/kg), mid (1.0 mg/kg), or high dose (5 mg/kg) adalimumab or 5 mg/kg infliximab subcutaneous (SC) over a period of 8 weeks. After first and last dosing, pharmacokinetic analysis was performed. Anti-drug antibodies (ADAs) were measured on several time points. Furthermore, hematology, clinical chemistry, body weight, clinical signs, and histopathology of several organs were evaluated. No signs of toxicity of the treatments were observed in the limited organs and tissues collected. Eleven out of 12 minipigs treated with adalimumab elicited a detectable ADA response. Induction of ADA was correlated with decreased plasma levels of adalimumab. Infliximab clearance was comparable after first and last dose. Therefore, the presence of ADA directed to infliximab was considered highly unlikely. It was concluded that the minipig and NHP showed comparable suitability for immunogenicity prediction in humans. More studies with other biopharmaceutical products are needed to strengthen the status of the minipig as an alternative model for immunotoxicity testing including immunogenicity.
Chronic Elevation of Parathyroid Hormone in Mice Reduces Expression of Sclerostin by Osteocytes: A Novel Mechanism for Hormonal Control of Osteoblastogenesis (2005)

Both chronic excess of PTH, as in hyperparathyroidism, and intermittent elevation of PTH (by daily injections) increase the number of osteoblasts; albeit, the former is associated with bone catabolism and the later with bone anabolism. Intermittent PTH increases osteoblast number by attenuating osteoblast apoptosis, an effect that requires the transcription factor Runx2. However, chronic elevation of PTH does not affect osteoblast apoptosis because it stimulates the proteasomal degradation of Runx2. Here, we studied the effects of PTH on Sost, a Runx2 target gene expressed in osteocytes (former osteoblasts embedded in the bone matrix), which antagonizes the pro-osteoblastogenic actions of bone morphogenetic proteins and Wnts. We report that continuous infusion of PTH to mice for 4 d decreased Sost mRNA expression in vertebral bone by 80-90%. This effect was accompanied by a comparable reduction of sclerostin, the product of Sost, in osteocytes, as determined by quantitative immunoblot analysis of bone extracts and by immunostaining. In contrast, a single injection of PTH caused a transient 50% reduction in Sost mRNA at 2 h, but four daily injections had no effect on Sost mRNA or sclerostin. PTH strongly decreased Sost expression in osteocytes formed in primary cultures of neonatal murine calvaria cells as well as in osteocytic MLO-A5 cells, demonstrating a direct effect of PTH on this cell type. These results, together with evidence that sclerostin antagonizes bone morphogenetic proteins and Wnts, strongly suggest that suppression of Sost by PTH represents a novel mechanism for hormonal control of osteoblastogenesis mediated by osteocytes.
Current status of multiple antigen-presenting peptide vaccine systems: Application of organic and inorganic nanoparticles (2011)

Many studies are currently investigating the development of safe and effective vaccines to prevent various infectious diseases. Multiple antigen-presenting peptide vaccine systems have been developed to avoid the adverse effects associated with conventional vaccines (i.e., live-attenuated, killed or inactivated pathogens), carrier proteins and cytotoxic adjuvants. Recently, two main approaches have been used to develop multiple antigen-presenting peptide vaccine systems: (1) the addition of functional components, e.g., T-cell epitopes, cell-penetrating peptides, and lipophilic moieties; and (2) synthetic approaches using size-defined nanomaterials, e.g., self-assembling peptides, non-peptidic dendrimers, and gold nanoparticles, as antigen-displaying platforms. This review summarizes the recent experimental studies directed to the development of multiple antigen-presenting peptide vaccine systems.
Thrombolytic Therapy (1988)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Glucose clamp technique: a method for quantifying insulin secretion and resistance. (1979)

Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
Influence of converting enzyme inhibition on renal hemodynamics and glomerular dynamics in sodium-restricted dogs. (1982)

Clearance and micropuncture experiments were performed to evaluate the influence of converting enzyme inhibition (CEI) (SQ 14,225) on renal hemodynamics, glomerular filtration rate (GFR), segmental vascular resistances, and superficial nephron function in anesthetized sodium restricted dogs. In one series (n = 8), renal blood flow (RBF) and GFR exhibited a high degree of autoregulatory efficiency when renal arterial pressure (RAP) was reduced from 126 +/- 5 to 86 +/- 1 mm Hg. With RAP maintained at the reduced level, CEI elicited increases in RBF (3.9 +/- 0.3 to 5.8 +/- 0.5 ml/min per g kw) and GFR (0.81 +/- 0.03 to 0.94 +/- 0.04 ml/min per g kw). With return of RAP to spontaneous levels during continued CEI, RBF and GFR autoregulatory efficiency was maintained, and was similar to that observed in control dogs subjected to the same procedures (n = 5). In the micropuncture experiments (n = 12), RAP was maintained at the reduced level (87.5 +/- .9 mm Hg), and measurements were made before and during CEI. Proximal tubule pressure, peritubular capillary pressure, stop flow pressure, and single nephron GFR (SNGFR) increased significantly. Regression analysis suggested that the increases in SNGFR were associated with small increases in the filtration coefficient. CEI reduced preglomerular resistance by 29% to 35% and efferent arteriolar resistance by 24% to 32%. These results indicate that the increased activity of the renin-angiotensin system that occurs during salt restriction exerts approximately equivalent vasoconstrictor influences on both preglomerular and postglomerular vascular resistance elements.
Ion channel targeting in neurons (1997)

Electrical signaling by neurons depends on the precisely ordered distribution of a wide variety of ion channels on the neuronal surface. The mechanisms underlying the targeting of particular classes of ion channels to specific subcellular sites are poorly understood. Recent studies have identified a new class of protein-protein interaction mediated by PDZ domains, protein binding modules that recognize specific sequences at the C terminus of membrane proteins. The PDZ domains of a family of synaptic cytoskeleton-associated proteins, typified by PSD-95, bind to the intracellular C-terminal tails of NMDA receptors and Shaker-type K+ channels. This interaction appears to be important in the clustering and localization of these ion channels at synaptic sites. Recognition of specific C-terminal peptide sequences by different PDZ domain-containing proteins may be a general mechanism for differential targeting of proteins to a variety of subcellular locations.
Age-related macular degeneration (AMD): pathogenesis and therapy. (2006)

Age-related macular degeneration (AMD) is a disease leading to severe visual loss and legal blindness in the elderly population. Its pathogenesis, likely multifactorial, involving a complex interaction of metabolic, functional, genetic and environmental factors, remains poorly understood. For these reasons currently used therapeutic approaches are insufficiently effective. Although major abnormalities are seen in four functionally interrelated tissues, i.e., photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaries, the impairment of RPE cell functions is an early and crucial event in the molecular pathways leading to clinically relevant AMD changes. RPE progressively degenerate, which results in a progressive irreversible degeneration of photoreceptors. Four processes: lipofuscinogenesis, drusogenesis, inflammation and neovascularization, specifically contribute to the development of two forms of AMD, the dry form (non-exudative; geographic atrophy) and the wet form (exudative, neovascular). This paper briefly describes major molecular and cellular events leading to AMD, and presents currently used and new experimental, forthcoming therapeutic strategies.
High frequency of the apolipoprotein E *4 allele in African pygmies and most of the African populations in sub-Saharan Africa. (1997)

Apolipoprotein E genotypes (alleles *2, *3, and *4) have been determined in 70 Aka Pygmies and 470 unrelated African sub-Saharan subjects. Allele frequencies for Pygmies are 5.7% for APOE*2, 53.6% for APOE*3, and 40.7% for APOE*4, and the global proportions for sub-Saharan subjects are 11.6% for APOE*2, 70.6% for APOE*3, and 17.8% for APOE*4. The frequencies in some ethnic groups are statistically different from the overall mean in the Afar and the Isa, the Ewe (Togo), the Malinke (Guinea), and the Mossi; three ethnic groups have a higher allele frequency of APOE*4 (Fon, 29.4%; Zairians, 33.3%; Tutsi, 38.5%). The APOE*4 allele is considered the ancestral form because of its high frequency in African Pygmies and other aboriginal populations.
Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility (2020)

Besides satisfying Koch's postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.
InP on Si(111): Accommodation of lattice mismatch and structural properties (1994)

The growth of InP by low-pressure metalorganic chemical vapor deposition on vicinal Si(111), misoriented 3° towards [1̄1̄2], is reported. By double crystal x-ray diffraction an order of magnitude improvement in structural quality is measured as compared to InP on Si(001). From high resolution electron microscopy near the interface a heavily twinned region of 25 nm in thickness is found with microtwins having their twin planes parallel to the Si(111) surface. In this region the 8% misfit between InP and Si is completely accommodated in one dimension by partial dislocations having Burgers vectors a/6〈112〉 (Schockley partial dislocations) in the (111) surface plane which are associated with the formation of the thin twinned region close to the interface. Above this zone the crystallographic orientations of the InP are identical to those of the Si substrate.
Physicochemical characterization of deposits associated with HA ceramics implanted in nonosseous sites (1988)

Pellets of well-characterized microporous hydroxyapatite (HA) ceramic were implanted in hamsters in two nonosseous sites: (1) in the fatty tissue of the gingival crease, far from bony tissue and (2) in intraperitoneal sites. The implants in site 1 were placed directly in contact with tissues, cells, and extracellular fluids while the implants in site 2 were placed in special chambers made of plexiglass cylinders covered in both ends with millipore filters, preventing contact with tissues and cells, but not with extracellular fluids. The hamsters were sacrificed and the implants recovered after 8, 16, 30, 150, and 365 days. The pellets were characterized using x-ray diffraction, infrared absorption, thermogravimetry, scanning and transmission electron microscopy, and calcium and phosphate analyses before and after implantation. Physicochemical analyses of HA ceramic implants before and after implantation demonstrated the formation of new material which was significantly different from the HA ceramic in terms of the following: (a) morphology (size of shape) of crystals; (b) intimate association of the inorganic phase of the new material with an organic phase similar to inorganic/organic association in bone; (c) the inorganic phase of the new material is a CO3-apatite, similar to that of bone, while the HA in ceramic is CO3-free; (d) electron diffraction of apatite of new material is similar to that of bone apatite. This study also demonstrated that the new material associated with the HA ceramics implanted in two different nonosseous sites were identical in spite of the differences in their microenvironment (cellular and acellular).
Mdct-Based Coder For Highly Adaptive Speech And Audio Coding (2009)

Publication in the conference proceedings of EUSIPCO, Glasgow, Scotland, 2009
SF3B1 Mutations Are Associated with Alternative Splicing in Uveal Melanoma (2013)

Our data show that despite its dismal prognosis, uveal melanoma is a relatively simple genetic disease characterized by recurrent chromosomal losses and gains and a low mutational burden. We show that SF3B1 is recurrently mutated in uveal melanoma, and the mutations are associated with aberrant alternative splicing.
US28 Is a Potent Activator of Phospholipase C during HCMV Infection of Clinically Relevant Target Cells (2012)

Members of the cytomegalovirus family each encode two or more genes with significant homology to G-protein coupled receptors (GPCRs). In rodent models of pathogenesis, these viral encoded GPCRs play functionally significant roles, as their deletion results in crippled viruses that cannot traffic properly and/or replicate in virally important target cells. Of the four HCMV encoded GPCRs, US28 has garnered the most attention due to the fact that it exhibits both agonist-independent and agonist-dependent signaling activity and has been demonstrated to promote cellular migration and proliferation. Thus, it appears that the CMV GPCRs play important roles in viral replication in vivo as well as promote the development of virus-associated pathology. In the current study we have utilized a series of HCMV/US28 recombinants to investigate the expression profile and signaling activities of US28 in a number of cell types relevant to HCMV infection including smooth muscle cells, endothelial cells and cells derived from glioblastoma multiforme (GBM) tumors. The results indicate that US28 is expressed and exhibits constitutive agonist-independent signaling activity through PLC-β in all cell types tested. Moreover, while CCL5/RANTES and CX3CL1/Fractalkine both promote US28-dependent Ca(++) release in smooth muscle cells, this agonist-dependent effect appears to be cell-specific as we fail to detect US28 driven Ca(++) release in the GBM cells. We have also investigated the effects of US28 on signaling via endogenous GPCRs including those in the LPA receptor family. Our data indicate that US28 can enhance signaling via endogenous LPA receptors. Taken together, our results indicate that US28 induces a variety of signaling events in all cell types tested suggesting that US28 signaling likely plays a significant role during HCMV infection and dissemination in vivo.
A six degree of freedom nanomanipulator design based on carbon nanotube bundles (2010)

Scanning probe imaging and manipulation of matter is of crucial importance for nanoscale science and technology. However, its resolution and ability to manipulate matter at the atomic scale is limited by rather poor control over the fine structure of the probe. In the present paper, a strategy is proposed to construct a molecular nanomanipulator from ultrathin single-walled carbon nanotubes. Covalent modification of a nanotube cap at predetermined atomic sites makes the nanotube act as a support for a functional 'tooltip' molecule. Then, a small bundle of nanotubes (three or four) with aligned ends can act as an extremely high aspect ratio parallel nanomanipulator for a suspended molecule, where protraction or retraction of individual nanotubes results in controlled tilting of the tooltip in two dimensions. Together with the usual scanning probe microscopy three degrees of freedom and augmented with rotation of the system as a whole, the design offers six degrees of freedom for imaging and manipulation of matter with the precision and freedom so much needed for advanced nanotechnology. A similar design might be possible to implement with other high aspect ratio nanostructures, such as oxide nanowires.
Combined Application of Cisplatin, Vindesine, Hyaluronidase and Radiation for Treatment of Advanced Squamous Cell Carcinoma of the Head and Neck (1995)

In a prospective pilot study, 32 patients with advanced inoperable squamous cell carcinoma of the head and neck were treated with polychemotherapy and hyaluronidase combined with radiation therapy. Polychemotherapy consisted of 5 mg vindesine on day 1 and 80 mg/m2 cisplatin on day 2. The patients were given 200,000 IU hyaluronidase intravenously 20 minutes prior to vindesine and cisplatin. Radiation in fractions of 2 Gy per day was administered on the following days (days 3-5, 8-12, 15-18), that is, 12 times. This regimen was repeated twice starting with day 22 and 43. Side effects were mainly of local character: moderate to severe mucositis in 10 patients and mild mucositis in 22 patients. No severe systemic toxicity was observed. Complete remission was achieved in 27 of 32 patients. At present, 16 patients are alive and without relapse. The average time of follow-up is 47 months (range: 26-75 months). These preliminary results suggest that combined therapy with vindesine, cisplatin, hyaluronidase, and radiation are well tolerated by most patients and highly effective against advanced squamous cell cancer of the head and the neck.