gebhart/patrepeval huggingface dataset:
Automated determination of arterial input function for DCE-MRI of the prostate (2011)

Prostate cancer is one of the commonest cancers in the world. Dynamic contrast enhanced MRI (DCE-MRI) provides an opportunity for non-invasive diagnosis, staging, and treatment monitoring. Quantitative analysis of DCE-MRI relies on determination of an accurate arterial input function (AIF). Although several methods for automated AIF detection have been proposed in literature, none are optimized for use in prostate DCE-MRI, which is particularly challenging due to large spatial signal inhomogeneity. In this paper, we propose a fully automated method for determining the AIF from prostate DCE-MRI. Our method is based on modeling pixel uptake curves as gamma variate functions (GVF). First, we analytically compute bounds on GVF parameters for more robust fitting. Next, we approximate a GVF for each pixel based on local time domain information, and eliminate the pixels with false estimated AIFs using the deduced upper and lower bounds. This makes the algorithm robust to signal inhomogeneity. After that, according to spatial information such as similarity and distance between pixels, we formulate the global AIF selection as an energy minimization problem and solve it using a message passing algorithm to further rule out the weak pixels and optimize the detected AIF. Our method is fully automated without training or a priori setting of parameters. Experimental results on clinical data have shown that our method obtained promising detection accuracy (all detected pixels inside major arteries), and a very good match with expert traced manual AIF.
Chimeric Antigen Receptor T Cell–Mediated Neurotoxicity in Nonhuman Primates (2018)

Chimeric antigen receptor (CAR) T-cell immunotherapy has revolutionized the treatment of refractory leukemias and lymphomas, but is associated with significant toxicities, namely cytokine release syndrome (CRS) and neurotoxicity. A major barrier to developing therapeutics to prevent CAR T cell-mediated neurotoxicity is the lack of clinically relevant models. Accordingly, we developed a rhesus macaque (RM) model of neurotoxicity via adoptive transfer of autologous CD20-specific CAR T cells. Following cyclophosphamide lymphodepletion, CD20 CAR T cells expand to 272 to 4,450 cells/μL after 7 to 8 days and elicit CRS and neurotoxicity. Toxicities are associated with elevated serum IL6, IL8, IL1RA, MIG, and I-TAC levels, and disproportionately high cerebrospinal fluid (CSF) IL6, IL2, GM-CSF, and VEGF levels. During neurotoxicity, both CD20 CAR and non-CAR T cells accumulate in the CSF and in the brain parenchyma. This RM model demonstrates that CAR T cell-mediated neurotoxicity is associated with proinflammatory CSF cytokines and a pan-T cell encephalitis.<b>Significance:</b> We provide the first immunologically relevant, nonhuman primate model of B cell-directed CAR T-cell therapy-mediated CRS and neurotoxicity. We demonstrate CAR and non-CAR T-cell infiltration in the CSF and in the brain during neurotoxicity resulting in pan-encephalitis, accompanied by increased levels of proinflammatory cytokines in the CSF. <i>Cancer Discov; 8(6); 750-63. ©2018 AACR.</i><i>This article is highlighted in the In This Issue feature, p. 663</i>.
Participation of acetaldehyde dehydrogenases in ethanol and pyruvate metabolism of the yeast Saccharomyces cerevisiae (2001)

This work was undertaken to clarify the role of acetaldehyde dehydrogenases in Saccharomyces cerevisiae metabolism during growth on respiratory substrates. Until now, there has been little agreement concerning the ability of mutants deleted in gene ALD4, encoding mitochondrial acetaldehyde dehydrogenase, to grow on ethanol. Therefore we constructed mutants in two parental strains (YPH499 and W303-1a). Some differences appeared in the growth characteristics of mutants obtained from these two parental strains. For these experiments we used ethanol, pyruvate or lactate as substrates. Mitochondria can oxidize lactate into pyruvate using an ATP synthesis-coupled pathway. The ald4Delta mutant derived from the YPH499 strain failed to grow on ethanol, but growth was possible for the ald4Delta mutant derived from the W303-1a strain. The co-disruption of ALD4 and PDA1 (encoding subunit E1alpha of pyruvate dehydrogenase) prevented the growth on pyruvate for both strains but prevented growth on lactate only in the double mutant derived from the YPH499 strain, indicating that the mutation effects are strain-dependent. To understand these differences, we measured the enzyme content of these different strains. We found the following: (a) the activity of cytosolic acetaldehyde dehydrogenase in YPH499 was relatively low compared to the W303-1a strain; (b) it was possible to restore the growth of the mutant derived from YPH499 either by addition of acetate in the media or by introduction into this mutant of a multicopy plasmid carrying the ALD6 gene encoding cytosolic acetaldehyde dehydrogenase. Therefore, the lack of growth of the mutant derived from the YPH499 strain seemed to be related to the low activity of acetaldehyde oxidation. Therefore, when cultured on ethanol, the cytosolic acetaldehyde dehydrogenase can partially compensate for the lack of mitochondrial acetaldehyde dehydrogenase only when the activity of the cytosolic enzyme is sufficient. However, when cultured on pyruvate and in the absence of pyruvate dehydrogenase, the cytosolic acetaldehyde dehydrogenase cannot compensate for the lack of the mitochondrial enzyme because the mitochondrial form produces intramitochondrial NADH and consequently ATP through oxidative phosphorylation.
Concentration of vascular endothelial growth factor in the serum and tumor tissue of brain tumor patients. (1996)

Vascular endothelial growth factor (VEGF) has been investigated as a potent mediator of brain tumor angiogenesis, vascular permeability, and glioma growth. Using a VEGF ELISA, we determined the concentration of VEGF in the sera and tumor extracts of 19 brain tumor patients including glioblastoma, anaplastic astrocytoma, low grade astrocytoma, meningioma, malignant lymphoma, and metastatic brain tumor as well as normal brain. Although VEGF concentration of the serum was not correlated with that of the tissue, VEGF concentrations of glioblastoma cyst fluid were 200-300-fold higher than those of serum in the patients. VEGF concentration in the tumors was significantly correlated with the vascularity measured by counting vessels stained with von Willebrand factor antibody. VEGF protein localized to the cytoplasm of tumor cells and vasculature in gliomas, predominantly in the peripheral microvessel "hot spots" as well as around the necrosis in glioblastomas. VEGF immunopositivities were well reflected with VEGF concentration determined by ELISA. VEGF ELISA demonstrated time-dependent increase of the VEGF concentration in the serum-free conditioned medium of various glioma cell lines. The conditioned medium with high VEGF concentration induced endothelial cell migration. These observations suggest that VEGF represents a useful marker and measurable element of glioblastoma angiogenesis. The measurement of VEGF concentration by ELISA in tumor and tumor cyst fluid may allow for the assessment of vascularity in gliomas.
Structural characterization of human alpha2-macroglobulin subunits. (1979)

Human crz-macroglobulin (azM) (>98% a single component) was isolated in gram quantities using polyethylene glycol, ammonium sulfate, and ion exchange fractionation of outdated human plasma.To determine the number and similarity of subunits in the native protein, quantitative repetitive Edman degradation was performed.The single, unique sequence was found to be: NHz-Ser-Val-Ser-Gly-Lys-Pro-Ghr-Tyr-Met-Val-Leu-Val-Pro-.The sequence was quantitated to 3.2 mol of NH&erminal residues/M, = 725,000.Carboxypeptidase Y digestion of lvzM released seven different amino acids in a time-dependent pattern and in quantities approaching 4 mol of amino acid/M= = 725,000.The following COOH-terminal sequence was assigned from the results, -Be-Phe-(Ala,Tyr)-(Glu,Val)-Leu-COOH.Radioautography of tryptic peptide maps of [2-14C]carboxymethylated aaM revealed 20 to 23 radiodense spots, which is consistent with a single subunit ofM, = 185,000 containing 28 cysteinyl residues (one-fourth of the native molecular weight).These data, for the first time, provide chemical evidence that azM is composed of four identical, M, = 185,000 peptide chains.Using our highly purified arzM and carefully quantitated trypsin, LY~M was found to inhibit 1.7 to 2.1 mol of trypsin/Cchain native aaM.Concomitant with trypsin binding, all four peptide chains were hydrolyzed to two M, = 85,000 fragments.This indicates that two peptide chains are cleaved per molecule of trypsin bound.
Characterization and Functional Analysis of 12 Naturally Occurring Reactive Site Variants of Serpin-1 from Manduca sexta (1997)

Serpin gene-1 from the tobacco hornworm, Manduca sexta, encodes, through alternative exon usage, 12 reactive site variants (Jiang, H., Wang, Y. and Kanost, M. R., (1994) J. Biol. Chem. 269, 55-58; Jiang, H., Wang, Y., Huang, Y., Mulnix, A. B., Kadel, J., Cole, K., and Kanost, M. R. (1996) J. Biol. Chem. 271, 28017-28023). These 43-kDa proteins differ from each other only in their COOH-terminal 39-46 residues, which include the reactive site. To test the hypothesis that these proteins are proteinase inhibitors of diverse selectivities and to begin to elucidate their physiological functions, we expressed the 12 serpin-1 variants in Escherichia coli. Seven of the variants inhibited mammalian serine proteinases, with association rate constants comparable with those of human serpins. Serpin-1A, with a P1 Arg residue, inhibited both trypsin and plasmin. Serpin-1B (P1 Ala) and serpin-1F (P1 Val) inhibited porcine pancreatic elastase and human neutrophil elastase. Serpin-1H, -1K, and -1Z, all with a Tyr residue at the P1 position, inhibited chymotrypsin and cathepsin G. Serpin-1I (P1 Leu) inhibited both elastase and chymotrypsin. Nine of the serpin variants were active as inhibitors of microbial serine proteinases, including subtilisin Carlsberg, proteinase K, and two proteinases secreted by an entomopathogenic fungus, Metarhizium anisopliae. In addition, one of the serpin variants, serpin-1J, strongly inhibited activation of M. sexta hemolymph phenoloxidase, a pathway involving a serine proteinase cascade. This pathway is a component of the defensive response of insects to microbial infection. These results suggest that the products of M. sexta serpin gene-1 may be important in regulating both exogenous and endogenous serine proteinases in hemolymph.
The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated with increased tyrosine phosphorylation and the recruitment of both pp125FAK and protein kinase C-δ to focal adhesions (1994)

Mouse Swiss 3T3 fibroblasts cultured in serum-free medium lose their actin stress fibres and vinculin-containing focal adhesions, a process that can be reversed by the addition of serum, lysophosphatidic acid (LPA) or bombesin, and is mediated by rhoA (A. J. Ridley and A. Hall (1992) Cell 70, 389-399). We have shown that the addition of serum to these cells induces the recruitment of the cytoskeletal proteins talin, vinculin and paxillin, and the protein kinases pp125FAK and PKC-delta, to newly formed focal adhesions, and that alpha-actinin is distributed along the actin stress fibres associated with these structures. The newly formed focal adhesions stained heavily with an antibody to phosphotyrosine. A similar response was elicited by 100 ng/ml LPA. The effect of serum was rapid, with focal staining for paxillin largely restricted to cell margins seen within 2 minutes of serum addition, and preceding the assembly of actin filaments. Phosphotyrosine staining differed in that it was predominantly punctate and was widely distributed throughout the cell. By 5 minutes, the paxillin and phosphotyrosine staining was concentrated at the ends of actin filaments largely at the cell margins. The structures stained ranged from circular to oval, but by 10 minutes they more closely resembled the elongated focal adhesions found in cultured fibroblasts. Within 10 minutes, the addition of serum or LPA induced a marked increase in the levels of pp125FAK and paxillin immune-precipitated by an anti-phosphotyrosine antibody. The results suggest that both pp125FAK and paxillin undergo changes in tyrosine phosphorylation upon activation of rhoA, and that these changes are associated with the assembly of focal adhesions and actin stress fibres. The observation that formation of focal adhesions can be induced by the tyrosine phosphatase inhibitor vanadyl hydroperoxide is consistent with the direct involvement of tyrosine phosphorylation in the assembly process. The localisation of PKC-delta to newly formed focal adhesions suggests that serine/threonine phosphorylation may also be important in this regard.
Interleukin‐10 generation in atopic children following oral Lactobacillus rhamnosus GG (2000)

Oral Lactobacillus rhamnosus GG ingestion for 5 days to 4 weeks has been shown to alleviate clinical symptoms of gastrointestinal inflammation and atopic dermatitis. To determine whether oral Lactobacillus rhamnosus GG may act by generating immunosuppressive mediator in atopic children. Lactobacillus rhamnosus GG (ATCC 53103) at a daily dose of 2 x 1010 cfu was added for 4 weeks to the diets of nine children (mean age, 21 months) with atopic dermatitis. Blood and faecal samples were collected before supplementation and at early (2 weeks) and late stage (4 and 8 weeks from the beginning). The concentrations of interleukin-6 (IL-6), IL-10, IL-12, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) in sera, as well as the production of IL-2, IL-4, IL-10 and IFNgamma in mitogen-induced peripheral blood mononuclear cells, were assessed. Secretory IgA and TNFalpha were also determined in faeces. The serum IL-10 concentration differed significantly between before, early and late samples (P < 0.001) due to the elevation of serum IL-10 in the later phase of oral Lactobacillus rhamnosus GG ingestion. The enhancement of IL-10 production in mitogen-induced cultures preceded the rise in serum IL-10. The enhanced IL-10 generation in vivo substantiates the anti-inflammatory properties of specific probiotic bacteria strains, and provides an additional reason for considering such treatments for patients with intestinal inflammation.
Amelioration of collagen-induced arthritis in DBA/1J mice by recombinant TSG-6, a tumor necrosis factor/interleukin-1-inducible protein (2000)

The antiinflammatory effect of the TNF/IL-1-inducible TSG-6 protein in murine CIA suggests a role for this protein as an endogenous regulator of the inflammatory process.
The statistical significance of nucleotide position-weight matrix matches (1996)

The Mksite program was originally developed for analyzing protein sequences. We report NMksite, a new version adapted to the processing of nucleotide sequences. NMksite creates PWM from nucleotide sequence block alignments or occurrence tables using three weight computation schemes. An original feature of NMksite is the numerical computation of the statistical significance of PWM matches. The utility of this concept is demonstrated in the context of the prediction of splice sites and promoter regions.
Climbing, brachiation, and terrestrial quadrupedalism: Historical precursors of hominid bipedalism (1996)

The vertical-climbing account of the evolution of locomotor behavior and morphology in hominid ancestry is reexamined in light of recent behavioral, anatomical, and paleontological findings and a more firmly established phylogeny for the living apes. The behavioral record shows that African apes, when arboreal, are good vertical climbers, and that locomotion during traveling best separates the living apes into brachiators (gibbons), scrambling/ climbing/brachiators (orangutans), and terrestrial quadrupeds (gorillas and chimpanzees). The paleontological record documents frequent climbing as an ancestral catarrhine ability, while a reassessment of the morphology of the torso and forelimb in living apes and Atelini suggests that their shared unique morphological pattern is best explained by brachiation and forelimb suspensory positional behavior. Further, evidence from the hand and foot points to a terrestrial quadrupedal phase in hominoid evolution prior to the adoption of bipedalism. The evolution of positional behavior from early hominoids to hominids appears to have begun with an arboreal quadrupedal-climbing phase and proceeded though an orthograde, brachiating, forelimb-suspensory phase, which was in turn followed by arboreal and terrestrial quadrupedal phases prior to the advent of hominid bipedality. The thesis that protohominids climbed down from the trees to become terrestrial bipeds needs to be reexamined in light of a potentially long history of terrestriality in the ancestral protohominid.
Application specific beam profiles: new surface and thin-film refinement processes using beam shaping technologies (2017)

Today, the use of laser photons for materials processing is a key technology in nearly all industries. Most of the applications use circular beam shapes with Gaussian intensity distribution that is given by the resonator of the laser or by the power delivery via optical fibre. These beam shapes can be typically used for material removal with cutting or drilling and for selective removal of material layers with ablation processes. In addition to the removal of materials, it is possible to modify and improve the material properties in case the dose of laser photons and the resulting light-material interaction addresses a defined window of energy and dwell-time. These process windows have typically dwell-times between µs and s because of using sintering, melting, thermal diffusion or photon induced chemical and physical reaction mechanisms. Using beam shaping technologies the laser beam profiles can be adapted to the material properties and time-temperature and the space-temperature envelopes can be modified to enable selective annealing or crystallization of layers or surfaces. Especially the control of the process energy inside the beam and at its edges opens a large area of laser applications that can be addressed only with an optimized spatial and angular beam profile with down to sub-percent intensity variation used in e.g. immersion lithography tools with ArF laser sources. LIMO will present examples for new beam shapes and related material refinement processes even on large surfaces and give an overview about new mechanisms in laser material processing for current and coming industrial applications.
Direct transfer of transforming growth factor beta 1 gene into arteries stimulates fibrocellular hyperplasia. (1993)

The arterial wall responds to thrombosis or mechanical injury through the induction of specific gene products that increase cellular proliferation and connective tissue formation. These changes result in intimal hyperplasia that is observed in restenosis and the early phases of atherosclerosis. Transforming growth factor beta 1 (TGF-beta 1) is a secreted multi-functional protein that plays an important role in embryonal development and in repair following tissue injury. However, the function of TGF-beta 1 in vascular cell growth in vivo has not been defined. In this report, we have evaluated the role of TGF-beta 1 in the pathophysiology of intimal and medial hyperplasia by gene transfer of an expression plasmid encoding active TGF-beta 1 into porcine arteries. Expression of TGF-beta 1 in normal arteries resulted in substantial extracellular matrix production accompanied by intimal and medial hyperplasia. Increased procollagen, collagen, and proteoglycan synthesis in the neointima was demonstrated by immunohistochemistry relative to control transfected arteries. Expression of TGF-beta 1 induced a distinctly different program of gene expression and biologic response from the platelet-derived growth factor B (PDGF B) gene: procollagen synthesis induced by TGF-beta 1 was greater, and cellular proliferation was less prominent. These findings show that TGF-beta 1 differentially modulates extracellular matrix production and cellular proliferation in the arterial wall in vivo and could play a reparative role in the response to arterial injury.
Catalase Test Protocol (2010)

The catalase test is used to detect the presence of the enzyme catalase in bacteria. Catalase serves to neutralize the bactericidal effects of hydrogen peroxide. Its concentration in bacteria has been correlated with pathogenicity. This enzymatic test is essential in the scheme of identification for gram-positive organisms and certain gram-negative organisms. It is a primary test used in the differentiation of staphylococci and streptococci.
Mechanisms and Molecules that Control Growth Cone Guidance (1996)

Neuronal growth cones traverse long distances along appropriate pathways to find their correct targets. This review presents an overview of the mechanisms and molecules that control these events. Secreted and cell surface ligands in the growth cone's environment bind to receptors on the growth cone's surface, trigger second-messenger signals, and lead to appropriate steering decisions. Growth cones appear to be guided by at least four different mechanisms: contact-mediated attraction, chemoattraction, contact-mediated repulsion, and chemorepulsion. These mechanisms are mediated by many different families of guidance molecules, including neural cell adhesion molecules of the immunoglobulin superfamily, netrins, and semaphorins, all of which appear to be highly conserved from worms and fruitflies to mice and humans. We are just beginning to gain insights into the functions of these and other molecules in the developing organism by the use of genetic analysis.
Energetics and Vibrational States for Hydrogen on Pt(111) (2002)

We present a combination of theoretical calculations and experiments for the low-lying vibrational excitations of H and D atoms adsorbed on the Pt(111) surface. The vibrational band states are calculated based on the full three-dimensional adiabatic potential energy surface obtained from first-principles calculations. For coverages less than three quarters of a monolayer, the observed experimental high-resolution electron peaks at 31 and 68 meV are in excellent agreement with the theoretical transitions between selected bands. Our results convincingly demonstrate the need to go beyond the local harmonic oscillator picture to understand the dynamics of this system.
FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. (1987)

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.