gebhart/patrepeval huggingface dataset:
Registration of CAD-models to images by iterative inverse perspective matching (1996)

A new algorithm for registering a 3D model to a single or a sequence of 2D images without a-priori knowledge of correspondences is presented. The algorithm is composed of two iterated steps: the first step determines correspondences between image features and model data, while the second one computes the 3D rigid body transformation that minimizes the displacement of the matched points. As camera images do not yield full 3D information, the key idea proposed is to exploit the inverse perspective, i.e. the projection ray determined by the focal point of the camera and an image feature point. The inverse perspective yields the constraints for both correspondence search and pose estimation in 3D space rather than in the image plane. This not only simplifies the motion parameter estimation but also reduces matching ambiguities due to occlusions. In addition, a robust M-estimation technique reduces the impact of false correspondences. Experimental results show that complex, 3D CAD-models can be registered efficiently and accurately to images, even if image features are incomplete, fragmented and noisy.
Surface-active phospholipid as the lubricating component of lubricin (1998)

To resolve the apparent conflict between a lubricating glycoprotein, 'lubricin', as the active ingredient in synovial fluid (SF) and surface-active phospholipid (SAPL) present in SF (and adsorbed to articular cartilage) as the boundary lubricant reducing friction to such low physiological levels, lubricin was isolated from bovine SF following the original procedure of Swann et al. (Arthritis Rheum 1981;24:22-30). Analysis of the lipid extract by thin-layer chromatography and phosphorus determination demonstrated a phospholipid component of 11.1 +/- 1.7% (N = 5) which corresponds very closely to the 9.2-13.0% of lubricin which had hitherto remained unidentified and which has previously been shown to be transferable to the articular surface to impart lubrication. These results would appear to resolve any theoretical conflict in that lubricin is, indeed, an active ingredient within SF. Yet, as a large water-soluble molecule, it really functions as a carrier for the highly insoluble SAPL which it deposits on the articular surface as the oligolamellar layer visualized in previous studies. However, it is this deposited SAPL, rather than lubricin, which actually lubricates.
Isolated Limb Perfusion with Melphalan and TNF-α in the Treatment of Extremity Sarcoma (2007)

Isolated limb perfusion (ILP) with chemotherapy alone has uniformly failed in the treatment of irresectable extremity soft tissue sarcomas. The addition of tumor necrosis factor-alpha (TNF-alpha) to this treatment approach contributed to a major step forward in the treatment of locally advanced extremity soft tissue sarcoma (STS). High response rates and limb salvage rates have been reported in multicenter trials, which combined ILP with TNF-alpha plus melphalan, which resulted in the approval of TNF-alpha for this indication in Europe in 1998. Subsequently a series of confirmatory single institution reports on the efficacy of the procedure have now been published. TNF-alpha has an early and a late effect; it enhances tumor-selective drug uptake during the perfusion and plays an essential role in the subsequent selective destruction of the tumor vasculature. These effects result in a high response rate in high-grade soft tissue sarcomas. This induction therapy thus allows for resection of tumor remnants some 3 months after ILP and thus avoidance of limb amputation. TNF-alpha-based ILP is a well-established treatment to avoid amputations. It represents an important example of tumor vascularity-modulating combination therapy and should be offered in large volume tertiary referral centers.
Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections withCandida albicansandAspergillus fumigatus (2002)

Generation of oxidative products by phagocytic cells is known to be an important host defense mechanism directed toward killing of invading microorganisms. The importance of two major oxidant-producing enzymes, myeloperoxidase (MPO) and NADPH-oxidase, in in vivo fungicidal action was directly compared in genetically engineered mice. Both MPO-deficient (MPO-/-) and NADPH-oxidase-deficient (X-linked chronic granulomatous disease [X-CGD]) mice showed increased susceptibility to pulmonary infections with Candida albicans and Aspergillus fumigatus compared with normal mice, and the X-CGD mice exhibited shorter survivals than MPO-/- mice. This increased mortality of X-CGD mice was associated with a 10- to 100-fold increased outgrowth of the fungi in their organs during the first 6 days. These results suggest that superoxide (O2-) produced by NADPH-oxidase is more important than hypochlorous acid (HOCl) produced by MPO, although both oxidative products obviously contribute to the host defense against pulmonary infection with those fungi. We also observed that MPO-/-/X-CGD double knockout mice showed comparable levels of susceptibility to the X-CGD mice against C. albicans and A. funigatus, indicating that MPO is unable to play a role in host defense in the absence of NADPH-oxidase. This strongly suggests that hydrogen peroxide, the precursor of HOCl, is solely derived from O2- produced by NADPH-oxidase.
Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. (1984)

Cyclosporin A (CsA) is a potent immunosuppressive agent, now gaining wide application in human organ transplantation. The immunosuppressive activity of CsA is at least in part due to inhibition of lymphokine production by activated T lymphocytes. Specifically, inhibition of T-cell growth factor (TCGF; also designated interleukin 2) production appears to be an important pathway by which CsA impairs T-cell function. To define further both the specificity of CsA and the level at which it interferes with lymphokine gene expression, we have studied its effects on TCGF mRNA accumulation as well as TCGF gene transcription. These studies were performed with a cloned human leukemic T-cell line (Jurkat, subclone 32), which can be induced with phytohemagglutinin and phorbol 12-myristate 13-acetate to produce large amounts of TCGF. In these cells, high levels of TCGF mRNA were present in induced but not in uninduced Jurkat cells as judged by hybridization to a cloned human TCGF cDNA probe. CsA completely inhibited induced TCGF mRNA accumulation at concentrations of 0.3-1.0 microgram/ml, whereas low levels of appropriately sized TCGF mRNA were present at 0.01 microgram/ml. In nuclear transcription experiments, CsA inhibited the synthesis of TCGF transcripts in a dose-dependent manner with complete inhibition at a concentration of 1 microgram/ml. In contrast, CsA did not inhibit the expression of two other inducible genes, TCGF receptor and HT-3. Further, HLA gene expression was also less affected than TCGF in CsA-treated cells. These data suggest a relatively selective action of CsA on TCGF gene transcription.
Safety and Feasibility of Autologous Myoblast Transplantation in Patients With Ischemic Cardiomyopathy (2005)

These results demonstrate the survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality offers a potential therapeutic treatment for end-stage heart disease.
Thirteen-Week Oral Toxicity Study of l-Arginine in Rats (2004)

The amino acid L-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% (w/w) for both genders (males, 3.3 +/- 0.1 g/kg/day; females, 3.9 +/- 0.2 g/kg/day).
A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? (1999)

This is a review of the available information about drugs which cause an increase in plasma creatinine concentration without decreasing glomerular filtration rate (GFR). The GFR is the main, but not the single, determinant of the plasma creatinine levels. Several drugs, such as cimetidine, trimethoprim, corticosteroids, pyrimethamine, phenacemide, salicylates and active vitamin D metabolites, have been reported to increase plasma creatinine without influencing its glomerular filtration. Cimetidine, trimethoprim, pyrimethamine and salicylates can inhibit secretion of creatinine by the proximal tubule. Corticosteroids and vitamin D metabolites probably modify the production rate and the release of creatinine. The exact mechanism of phenacemide-creatinine interaction is not fully explained. These drug-induced alterations in plasma creatinine concentration have clinical significance when GFR is estimated by using plasma creatinine.
Local Features, All Grown Up (2006)

We present a technique to adapt the domain of local features through the matching process to augment their discriminative power. We start with local affine features selected and normalized independently in training and test images, and jointly expand their domain as part of the correspondence process, akin to a (non-rigid) registration task that yields a (multi-view) segmentation of the object of interest from clutter, including the detection of occlusions. We show how our growth process can be used to validate putative affine matches, to match a given "template" (an image of an object without clutter) to a cluttered and partially occluded image, and to match two images that contain the same unknown object in different clutter under different occlusions (unsupervised object detection).
The intracrine hypothesis and intracellular peptide hormone action (2003)

There is evidence that many peptide growth factors and hormones act in the intracellular space after either internalization or retention in their cells of synthesis. These factors, commonly called intracrines, are structurally diverse while sharing some common functional features. Reports of intracellular peptide hormone binding and action are reviewed here. Also, this laboratory has made proposals regarding the origin and actions of intracrines and these areas are further explored. Intracrine interactions and the relationship of intracrines to transcription factors are discussed. The intracellular/intracrine renin-angiotensin system (iRAS) is reviewed to illustrate the intracrine analogue of a well-established physiological system. The role of intracrine action in metazoan development is also considered.
GFP: from jellyfish to the Nobel prize and beyond (2009)

On December 10, 2008 Osamu Shimomura, Martin Chalfie and Roger Tsien were awarded the Nobel Prize in Chemistry for "the discovery and development of the green fluorescent protein, GFP". The path taken by this jellyfish protein to become one of the most useful tools in modern science and medicine is described. Osamu Shimomura painstakingly isolated GFP from hundreds of thousands of jellyfish, characterized the chromophore and elucidated the mechanism of Aequorean bioluminescence. Martin Chalfie expressed the protein in E. coli and C. elegans, and Roger Tsien developed a palette of fluorescent proteins that could be used in a myriad of applications.
Voltage Dependence of the Ca2+-activated Cation Channel TRPM4 (2003)

TRPM4 is a Ca2+-activated but Ca2+-impermeable cation channel. An increase of [Ca2+]i induces activation and subsequent reduction of currents through TRPM4 channels. This inactivation is strikingly decreased in cell-free patches. In whole cell and cell-free configuration, currents through TRPM4 deactivate rapidly at negative potentials. At positive potentials, currents are much larger and activate slowly. This voltage-dependent behavior induces a striking outward rectification of the steady state currents. The instantaneous current-voltage relationship, derived from the amplitude of tail currents following a prepulse to positive potentials, is linear. Currents show a Boltzmann type of activation; the fraction of open channels increases at positive potentials and is low at negative potentials. Voltage dependence is not due to block by divalent cations or to voltage-dependent binding of intracellular Ca2+ to an activator site, indicating that TRPM4 is a transient receptor potential channel with an intrinsic voltage-sensing mechanism. Voltage dependence of TRPM4 may be functionally important, especially in excitable tissues generating plateau-like or bursting action potentials.
Investigations on plasma activity of low molecular weight heparin after intravenous and oral administrations. (1989)

This study investigated the absorption of low molecular weight heparin (LMWH) after oral administration in man. Six healthy subjects received 5,000 anti-Xa units of LMWH (Kabi 2165) by both i.v. and oral administration. The oral formulations were prepared in pH 4.0 and pH 7.0 buffered solutions. Multiple blood samples were collected after each dose for measurements of anti-Xa, anti-IIa and APTT plasma heparin activities. Pharmacokinetic parameters based on the anti-Xa activity measurements after the i.v. dose were as follows (mean +/- s.d.): t1/2, 1.82 +/- 0.23 h; V, 4.34 +/- 0.651; and CL, 28.0 +/- 6.2 ml min-1. Half-life values based on the anti-IIa and APTT activities were 1.63 +/- 0.43 and 1.09 +/- 0.51 h, respectively. Considerable prolongations in APTT were observed, with APTT at 30 min averaging 55.7 +/- 4.1 s (1.84 +/- 0.27 times baseline values). After oral administration, no measurable plasma heparin activities were observed with either LMWH preparation. The results of this investigation indicate that LMWH does not have detectable plasma activity after oral administration, and that after i.v. administration it has significant anti-IIa and APTT activities in addition to its anti-Xa activity.
Glycosyl phosphatidylinositol membrane anchoring of melanotransferrin (p97): apical compartmentalization in intestinal epithelial cells (1993)

Melanotransferrin (p97) is an iron-binding membrane glycoprotein with 40% homology to transferrin and lactoferrin. It was first identified on the basis of its high level of expression in melanoma cells, as compared to normal melanocytes. It is also present in many cultured cell types. In normal tissues, p97 is expressed in fetal intestine, umbilical cord, sweat gland ducts and liver sinusoidal lining cells. Kinetic studies in melanoma cells have suggested that p97 plays a role in iron metabolism. We have examined expression of p97 in cell lines derived from human colorectal carcinomas which express a differentiated phenotype. When polarized, these cells showed a preferred apical distribution of p97, as demonstrated by immunohistochemistry, immune electron microscopy and domain-selective biotinylation. Correspondingly, p97 was only found on the apical brush border of epithelial cells in the fetal intestine. p97 was shown to be anchored to the membrane through a glycosyl phosphatidylinositol moiety by treatment with phophatidylinositol-specific phospholipase C (PI-PLC) and labeling with [14C]ethanolamine. These observations provide a basis for the elucidation of the physiological role of p97 in iron metabolism and its possible role in cell proliferation and malignant cell transformation.
Stereoselective Pharmacokinetic Analysis of the Antiepileptic 10-Hydroxycarbazepine in Dogs (1999)

The active entity of the new antiepileptic drug, oxcarbazepine (OXC), is 10-hydroxycarbazepine (MHD). In humans, OXC undergoes rapid presystemic (first-pass) metabolic reduction to MHD. MHD is a chiral molecule with an asymmetric carbon at position 10. Previous reports have shown that in humans, the first-pass metabolic reduction of OXC into MHD is stereoselective, resulting in a 1-to-4 AUC ratio of R(-) and S(+) enantiomers. The objective of the current study was to investigate whether the pharmacokinetics of MHD was stereoselective. Racemic MHD was thus administered intravenously (i.v.) and orally to six dogs, and plasma samples were analyzed by a stereospecific, high-performance liquid chromatographic (HPLC) assay. We found that R(-)-MHD had a clearance similar to that of S(+)-MHD; however, a difference was found between the volume of distribution (Vd) and consequently, between the half-lives of the two MHD enantiomers. The main pharmacokinetic parameters of R(-)- and S(+)-MHD were as follows: A terminal half-life (t1/2) of 2.2 +/- 0.4 hours for R(-)-MHD and of 3.8 +/- 0.3 hours for S(+)-MHD; a clearance (CL) of 7.8 +/- 1.3 L/h for R(-)-MHD and of 8.6 +/- 2.1 L/h for S(+)-MHD; a Vd of 25 +/- 6 L for R(-)-MHD and of 47 +/- 14 L for S(+)-MHD; and a Vd at steady state (V(ss)) of 22.8 +/- 3.6 for R(-)-MHD and of 29.9 +/- 4.1 for S(+)-MHD. After its oral administration to dogs, the absolute bioavailability was 78.4 +/- 20.9% for R(-)-MHD and 78.5 +/- 27.3% for S(+)-MHD; t1/2 was 2.7 +/- 0.6 hours for R(-)-MHD and 4.1 +/- 0.8 hours for S(+)-MHD. These results showed stereoselectivity in the volume of distribution and consequently, the t1/2 of S(+)-MHD was longer than that of R(-)-MHD after both i.v. and oral administration to dogs.
Evidence of Familial Association Between Attention Deficit Disorder and Major Affective Disorders (1991)

With the use of family study methods and assessments by "blinded" raters, we tested hypotheses about patterns of familial association between DSM-III attention deficit disorder (ADD) and affective disorders (AFFs) among first-degree relatives of clinically referred children and adolescents with ADD (73 probands, 264 relatives) and normal controls (26 probands, 92 relatives). Among the 73 ADD probands, 24 (33%) met criteria for AFFs (major depression, n = 15 [21%]; bipolar disorder, n = 8 [11%]; and dysthymia, n = 1 [1%]). After stratification of the ADD sample into those with AFFs (ADD + AFF) and those without AFF (ADD), familial risk analyses revealed the following: (1) the relatives of each ADD proband subgroup were at significantly greater risk for ADD than were relatives of normal controls; (2) the age-corrected morbidity risk for ADD was not significantly different between relatives of ADD and ADD + AFF (27% vs 22%); however, these two risks were significantly greater than the risk to relatives of normal controls (5%); (3) the risk for any AFF (bipolar disorder, major depressive disorder, or dysthymia) was not significantly different between relatives of ADD probands and ADD + AFF probands (28% and 25%), but these two risks were significantly greater than the risk to relatives of normal controls (4%); (4) ADD and AFFs did not cosegregate within families; and (5) there was no evidence for nonrandom mating. These findings are consistent with the hypothesis that ADD and AFFs may share common familial vulnerabilities.
The aryl hydrocarbon receptor directs hematopoietic progenitor cell expansion and differentiation (2013)

The evolutionarily conserved aryl hydrocarbon receptor (AhR) has been studied for its role in environmental chemical-induced toxicity. However, recent studies have demonstrated that the AhR may regulate the hematopoietic and immune systems during development in a cell-specific manner. These results, together with the absence of an in vitro model system enabling production of large numbers of primary human hematopoietic progenitor cells (HPs) capable of differentiating into megakaryocyte- and erythroid-lineage cells, motivated us to determine if AhR modulation could facilitate both progenitor cell expansion and megakaryocyte and erythroid cell differentiation. Using a novel, pluripotent stem cell-based, chemically-defined, serum and feeder cell-free culture system, we show that the AhR is expressed in HPs and that, remarkably, AhR activation drives an unprecedented expansion of HPs, megakaryocyte-lineage cells, and erythroid-lineage cells. Further AhR modulation within rapidly expanding progenitor cell populations directs cell fate, with chronic AhR agonism permissive to erythroid differentiation and acute antagonism favoring megakaryocyte specification. These results highlight the development of a new Good Manufacturing Practice-compliant platform for generating virtually unlimited numbers of human HPs with which to scrutinize red blood cell and platelet development, including the assessment of the role of the AhR critical cell fate decisions during hematopoiesis.
The Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor AG1478 Increases the Formation of Inactive Untethered EGFR Dimers (2006)

The epidermal growth factor receptor (EGFR) has at least two fundamental conformations: an inactive tethered conformation and an active untethered, ligand-bound "back-to-back" dimer, which may be part of an oligomeric complex. Monoclonal antibody (mAb) 806 is an EGFR-specific antibody that only binds a transitional form of the receptor after it untethers but before forming the back-to-back, ligated, active oligomer. We have shown that AG1478, a tyrosine kinase inhibitor of the EGFR, synergistically inhibits the growth of tumors overexpressing EGFR when used in combination with mAb 806 but the mechanism for this was not elucidated (Johns, T. G., Luwor, R. B., Murone, C., Walker, F., Weinstock, J., Vitali, A. A., Perera, R. M., Jungbluth, A. A., Stockert, E., Old, L. J., Nice, E. C., Burgess, A. W., and Scott, A. M. (2003) Proc. Natl. Acad. Sci. U. S. A. 100, 15871-15876). We now show that AG1478 increases binding of mAb 806 to the cell surface through two distinct mechanisms: an immediate effect on the conformation of EGFR and a longer term increase in cell surface under-glycosylated EGFR, an event known to increase mAb 806 reactivity. Cross-linking studies demonstrated the presence of spontaneously occurring mAb 806-reactive dimers on the surface of cells overexpressing EGFR, which are rapidly increased by AG1478. Because they react with mAb 806, these dimers must exist in a conformation distinct from the ligated back-to-back dimer. Indeed, we detected similar dimers in 293T cells expressing the EGFR lacking the small dimerization/activation arm essential to the formation of the back-to-back dimer. Thus, some of the EGFR on the cell surface of cancer cells must exist as an untethered dimer that adopts a previously unreported conformation that is inactive. This information was used to optimize the therapeutic synergy between mAb 806 and AG1478 in a xenograft model.