gebhart/patrepeval huggingface dataset:
Monitoring Kidney Transplant Patients (1983)

In the first two months following a kidney transplant, there are almost invariably rejection episodes, when the patient's body reacts negatively to the presence of the transplanted organ, resulting in a deterioration in functioning of the latter. Clinicians are therefore concerned to find some method of monitoring patients in order to detect sudden changes in the performance of the new kidney. Renal function is indicated by the glomerular filtration rate (GFR), which measures the rate at which various substances are cleared through the kidney, but GFR is not itself directly observable and so clinicians must attempt to infer something about it on the basis of blood or urine concentrations of chemicals for which kidney physiology suggests a simple form of relationship with GFR. This particular study is based on plasma creatinine measurements (Knapp et al., 1977). In a normally functioning kidney, GFR is constant and creatinine is excreted at a constant rate. In a recently transplanted kidney, typically fluctuating between periods of deterioration and improvement in functioning, GFR and plasma creatinine are inversely related. If GFR decreases, the observed concentration of creatinine will increase, and vice versa. In theory, therefore, by monitoring an observed plasma creatinine series for sudden changes it should be possible to infer the occurrence of significant underlying biological changes. In practice, messages in observed plasma creatinine series are obscured by a combination of factors which together add considerable noise to the underlying process. In part, these derive from biological variation and errors arising in the collection, measurement and processing of the data. In addition, however, there is more than one type of abrupt, discontinuous change in pattern which might occur and it is important to be able to distinguish these different forms of change. For this reason, a statistically based, automatic monitoring procedure requires considerable care in modelling the underlying system and observation processes. In particular, it requires the incorporation of substantial prior information based on physiological and clinical expertise. In section 2, we outline the model building process leading to a representation of the evolution of the plasma creatinine series in steady periods (either of improvement or deterioration). This model is extended, in section 3, to incorporate the various forms of discontinuity which may occur in the process. Section 4 summarizes the implementation of the monitoring procedure and section 5 outlines the way in which this procedure is used as a decision aid for clinicians. The emphasis in this paper is on the modelling process. Detailed mathematical developments are given in Smith and West (1983), detailed discussion of the clinical background and
Molecular identification of spadetail: regulation of zebrafish trunk and tail mesoderm formation by T-box genes (1998)

Inhibition of fibroblast growth factor (FGF) signaling prevents trunk and tail formation in Xenopus and zebrafish embryos. While the T-box transcription factor Brachyury (called No Tail in zebrafish) is a key mediator of FGF signaling in the notochord and tail, the pathways activated by FGF in non-notochordal trunk mesoderm have been uncertain. Previous studies have shown that the spadetail gene is required for non-notochordal trunk mesoderm formation; spadetail mutant embryos have major trunk mesoderm deficiencies, but relatively normal tail and notochord development. We demonstrate here that spadetail encodes a T-box transcription factor with homologues in Xenopus and chick. Spadetail is likely to be a key mediator of FGF signaling in trunk non-notochordal mesoderm, since spadetail expression is regulated by FGF signaling. Trunk and tail development are therefore dependent upon the complementary actions of two T-box genes, spadetail and no tail. We show that the regulatory hierarchy among spadetail, no tail and a third T-box gene, tbx6, are substantially different during trunk and tail mesoderm formation, and propose a genetic model that accounts for the regional phenotypes of spadetail and no tail mutants.
Use of E. coli lacZ (β-Galactosidase) as a Reporter Gene (2003)

Our understanding of the molecular mechanisms that govern gene expression has been facilitated by the ability to introduce recombinant DNA molecules into heterologous cellular systems both in vitro and in vivo. One approach to defining DNA sequences important in the regulation of gene expression is to place controlling elements (e.g., promoter/enhancer sequences) upstream of a DNA coding sequence, introduce these constructs into transgenic animals or cells in culture, and analyze the levels of gene product produced by the introduced construct. Ideally, such a reporter gene should encode a product that is stable, innocuous to the cell or organism in which it is being expressed, and should be readily detectable, even when present in small quantities.
Amino Acid Derivatives of β-Cyclodextrin (1996)

The syntheses of the heptaamino acid-substituted β-cyclodextrins per-6-[(phenylalanyl)amino]-β-cyclodextrin (6), per-6-cysteinyl-β-cyclodextrin (7), as well as the per-2,3-dimethyl-per-6-cysteinyl-β-cyclodextrin (12) are described. The amino acids were coupled to the primary face of the β-cyclodextrin torus using the backbone carboxylic acid functionality of phenylalanine and the side chain thiol group of cysteine. In the case of the heptacysteinyl derivatives, polyzwitterionic compounds were obtained and shown to be highly water soluble.
Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis (1995)

Uniparental disomy (UPD) in humans is caused primarily by meiotic nondisjunction events, followed by trisomy or monosomy 'rescue'. The majority of cases appear to be associated with advanced maternal age, and may be initially detected as mosaic trisomies during routine prenatal diagnosis by chorionic villus sampling or amniocentesis. In addition, structural abnormalities including Robertsonian translocations, reciprocal translocations and supernumerary marker chromosomes appear to be associated with an increased risk of UPD. Predicting the phenotypic effects of UPD is complex, as three independent factors are involved: (i) effects of trisomy on the placenta or the fetus; (ii) autosomal recessive disease due to reduction to homozygosity; and (iii) imprinted gene effects for some chromosomes. To date, UPD in humans has been reported for 25 of the 47 possible uniparental types. Imprinting effects have been established with certainty for four human chromosomes that have homology to mouse chromosomes which have been shown to have significant phenotypic effects in uniparental animals. A normal phenotype has been reported for 14 other UPD types. Thus, collection of data on UPD cases in humans is providing an imprinting map analogous to the experimentally derived imprinting map in mouse. This human imprinting map has important clinical implications, particularly in the area of prenatal diagnosis.
Cloning and Characterization of cDNA of Avirulence Geneavr9of the Fungal PathogenCladosporium fulvum, Causal Agent of Tomato Leaf Mold (1991)

A race-specific peptide elicitor from Cladosporium fulvum induces a hypersensitive response on Cf9 tomato genotypes. We have hypothesized that the avirulence of fungal races on Cf9 genotypes is due to the production of this elicitor by an avirulence gene, avr9. To obtain cDNA clones of the avr9 gene, oligonucleotide probes were designed based on the amino acid sequence determined previously. In northern blot analysis, one oligonucleotide detected an mRNA of 600 nucleotides in tomato-C. fulvum interactions involving fungal races producing the elicitor. A primer extension experiment indicated that the probe hybridized to a region near position 270 of the mRNA. The probe was used to screen a cDNA library made from poly(A)+ RNA from an appropriate compatible tomato-C. fulvum interaction. One clone was obtained corresponding to the mRNA detected by the oligonucleotide probe. Sequence analysis revealed that this clone encoded the avr9 elicitor. By isolating longer clones and by RNA sequencing, the primary structure of the mRNA was determined. The mRNA contains an open reading frame of 63 amino acids, including the sequence of the elicitor at the carboxyterminus. A time course experiment showed that the avr9 mRNA accumulates in a compatible tomato-C. fulvum interaction in correlation with the increase of fungal biomass. The avr9 gene is a single-copy gene that is absent in fungal races which are virulent on tomato Cf9 genotypes. Possible functions of the avirulence gene are discussed.
Specific penetration and accumulation of a homing peptide within atherosclerotic plaques of apolipoprotein E-deficient mice (2011)

The ability to selectively deliver compounds into atherosclerotic plaques would greatly benefit the detection and treatment of atherosclerotic disease. We describe such a delivery system based on a 9-amino acid cyclic peptide, LyP-1. LyP-1 was originally identified as a tumor-homing peptide that specifically recognizes tumor cells, tumor lymphatics, and tumor-associated macrophages. As the receptor for LyP-1, p32, is expressed in atherosclerotic plaques, we tested the ability of LyP-1 to home to plaques. Fluorescein-labeled LyP-1 was intravenously injected into apolipoprotein E (ApoE)-null mice that had been maintained on a high-fat diet to induce atherosclerosis. LyP-1 accumulated in the plaque interior, predominantly in macrophages. More than 60% of cells released from plaques were positive for LyP-1 fluorescence. Another plaque-homing peptide, CREKA, which binds to fibrin-fibronectin clots and accumulates at the surface of plaques, yielded fewer positive cells. Tissues that did not contain plaque yielded only traces of LyP-1(+) cells. LyP-1 was capable of delivering intravenously injected nanoparticles to plaques; we observed abundant accumulation of LyP-1-coated superparamagnetic iron oxide nanoparticles in the plaque interior, whereas CREKA-nanoworms remained at the surface of the plaques. Intravenous injection of 4-[(18)F]fluorobenzoic acid ([(18)F]FBA)-conjugated LyP-1 showed a four- to sixfold increase in peak PET activity in aortas containing plaques (0.31% ID/g) compared with aortas from normal mice injected with [(18)F]FBA-LyP-1(0.08% ID/g, P < 0.01) or aortas from atherosclerotic ApoE mice injected with [(18)F]FBA-labeled control peptide (0.05% ID/g, P < 0.001). These results indicate that LyP-1 is a promising agent for the targeting of atherosclerotic lesions.
Endothelial tubulogenesis within fibrin gels specifically requires the activity of membrane-type-matrix metalloproteinases (MT-MMPs) (2002)

Macro- and microvascular endothelial cells (EC) formed tubular structures when cultured within a 3D fibrin matrix, a process that was enhanced by vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), hepatocyte growth factor/scatter factor (HGF/SF) and an angiogenic cocktail composed of nine angiogenic factors. Endothelial tubulogenesis was also increased in co-culture with tumour cells such as U87 glioma cells, but not with non-tumorigenic cell types such as Madin-Darby canine kidney (MDCK) epithelial cells. VEGF/FGF-2-stimulated tube formation was dependent on metalloproteinase function [it is inhibited by the addition of tissue inhibitor of metalloproteinases-2 (TIMP-2)], whereas aprotinin, E64 [trans-epoxysuccinyl-L-leucylamido (4-guanidino)-butane] and pepstatin had no effect. In addition, TIMP-4 also inhibited tubulogenesis, but TIMP-1 or the C-terminal haemopexin domain of matrix metalloproteinase-2 (MMP-2) (PEX) and an anti-MMP-2 function-blocking antibody were unable to block tube formation. This suggests that MMP-2 and other soluble MMPs are not essential for tubulogenesis in fibrin gels, instead TIMP-1-insensitive MMPs, such as members of the membrane type-MMPs (MT-MMP) sub-group (MT1-, MT2-, MT3- or MT5-MMP), are required for this process. Further support for a role for MT1-MMP in endothelial tubulogenesis is that recombinant Y36G N-terminal TIMP-2 mutant protein, which retains an essentially unaltered apparent inhibition constant (K(i)(app)) for several MMPs compared to wild-type N-TIMP-2 but is a 40-fold poorer inhibitor of MT1-MMP, was unable to block tubulogenesis. Furthermore, when EC were cultured within fibrin gels, the mRNA levels of several MMPs (including MT1-MMP, MT2-MMP, MT3-MMP and MMP-2) increased during tubulogenesis. Therefore MT-MMPs and specifically MT1-MMP are likely candidates for involvement during endothelial tubulogenesis within a fibrin matrix, and thus their blockade may be a viable strategy for inhibition of angiogenesis.
Self-Assembled Films of Hydrophobin Proteins HFBI and HFBII Studied in Situ at the Air/Water Interface (2008)

Hydrophobins are a group of surface-active fungal proteins known to adsorb to the air/water interface and self-assemble into highly crystalline films. We characterized the self-assembled protein films of two hydrophobins, HFBI and HFBII from Trichoderma reesei, directly at the air/water interface using Brewster angle microscopy, grazing-incidence X-ray diffraction, and reflectivity. Already in zero surface pressure, HFBI and HFBII self-assembled into micrometer-sized rafts containing hexagonally ordered two-dimensional crystallites with lattice constants of 55 A and 56 A, respectively. Increasing the pressure did not change the ordering of the proteins in the crystallites. According to the reflectivity measurements, the thicknesses of the hydrophobin films were 28 A (HFBI) and 24 A (HFBII) at 20 mN/m. The stable films could also be transferred to a silicon substrate. Modeling of the diffraction data indicated that both hydrophobin films contained six molecules in the unit cell, but the ordering of the molecules was somewhat different for HFBI and HFBII, suggesting specific protein-protein interactions.
CA 125 in Benign Gynecological Conditions (1998)

The tumor marker CA 125 was initially thought to be specific for ovarian malignancies. Subsequently it was found to be raised in a variety of benign conditions, including pregnancy, pelvic inflammatory disease, tuberculosis and cirrhosis of the liver. With respect to gynecological tumors, CA 125 may be elevated in benign ovarian cysts, tubo-ovarian abscess, endometriosis, hyperstimulation syndrome, ectopic pregnancy and fibroids. These results demonstrate that CA 125 is a marker of non-specific peritoneal conditions.
Local Transfer of Diazepam, but Not of Cocaine, from the Nasal Cavities to the Brain Arterial Blood in Rats (2000)

Nasal administration to rats of small molecules (tritiated water, tyrosine, and propanol) results in a higher concentration in the brain arterial blood than in other arteries. The preferential distribution is based on a counter current transfer, which takes place between nasal vein blood and brain arterial blood in the cavernous sinus-carotid artery complex. The present experiments attempt to document that drugs may also be transferred by this system. Groups of 10 large male rats were anaesthetised and intubated. Two catheters were inserted into the same carotid artery, one tip pointing towards the head, the other towards the heart. Parallel blood samples were obtained every 30 sec. for 10 min. after nasal administration of radioactively labelled diazepam or cocaine, and the plasma radioactivity measured. Control groups received the drugs intravenously. The uptake of diazepam was rapid, while cocaine uptake was slow. The average ratio between the radioactivity of parallel samples (R: "Head" plasma/"Heart" plasma) in rats treated with nasal diazepam was 1.12+/-0.04, 181 (average+/-S.E.M., n) for the whole 10 min. period and 1.20+/-0.05, 96 for the second half of the sampling period. The increase of 12 and 20% is highly significant. The intravenous ratio for diazepam and both R's for the cocaine groups were not significantly different from 1.00. The present experiments show that nasal administration of diazepam induces a relatively higher concentration in the brain arterial blood than in parallel samples obtained from another artery. A preferential, first-pass distribution to the brain after nasal administration of diazepam may thus exist.
BACILLUS-CALMETTE-GUERIN (BCG) ORGANISMS DIRECTLY ALTER THE GROWTH OF BLADDER-TUMOR CELLS (1994)

Studies in recent years have shown various effects of bacillus Calmette Guerin organisms on the human immune system. In the present study, the direct effects of bacillus Calmette Guerin (BCG) (as used for the clinical management of superficial bladder cancer) on bladder tumour cells were investigated. Using a proliferation assay, changes in the growth rates of tumour cells were studied following direct exposure to BCG. The effects of variations in the BCG dose, and in the viability of BCG organisms were investigated and our initial observations concerning the antiproliferative effects of interferon-garnma were extended. The main finding of these studies is the direct immuno-modulatory effects of BCG organisms on the proliferative capacity of human tumour cells. Previously these alterations in the growth rate of bladder cancer cells, which are observed following patient therapy, were attributed to the production of various cytokines. However, after exposure to BCG the growth of tumour cell lines was suppressed in a dose and time dependent manner. Furthermore, both viable and nonviable bacilli can exert this action although heat killed BCG may be less effective in doing so. In concordance with our earlier study, interferon-gamma exerted marked antiproliferative effects against eight tumour cell lines. Furthermore, a 12 hour pulse of cytokine was sufficient to suppress the growth of tumour cells. This is an important finding as cytokine is not detected in patient's urine later than 12 hours after immunotherapy. No consistent pattern of growth altering effect was observed with any of the other cytokines tested (IL-1-alpha, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, GM-CSF). Our study suggests that BCG organisms per se may exert direct effects upon tumour cells in vivo and thus ease the load on the immune responses leading to the eventual eradication of tumour.
FM Demodulators in Software-Defined Radio Using FPGAs with Rapid Prototyping (2011)

With the advent of software-defined radio, many radio applications have and are currently being designed for FPGAs, due to their high performance and reconfigurability. Invariably, "legacy" waveforms, such as FM, will need to be supported in such systems. A challenge that comes with programming FPGAs is the increased design and implementation time over conventional software programming. In this thesis, three FM demodulator techniques are implemented and compared in an FPGA. Two techniques are found to have similar SNR performance while having very different FPGA implementation characteristics. Library based design is explored for demodulators to increase FPGA design productivity. A block library is created and verified by use in tested demodulator designs. Two design tools that aim to increase design productivity in FPGAs, Ogre and HMFlow, are also examined and used to implement FM demodulators in a PCM/FM receiver design. Ogre leverages the demodulator block library, along with accompanying metadata, to decrease design time significantly. Design performance is not sacrificed when using Ogre. HMFlow, which relies on finer-grained blocks, reuses block implementation data to speed up implementation of the full design. The implementation of the HMFlow demodulator design is sped up by 3x but, when compared with the standard flow, produces an implementation with a reduced maximum clock rate (about 1/2) and with slightly more resources (about 6%). When comparing Ogre with HMFlow, the coarser-grained blocks of Ogre provide a more efficient design experience than that of HMFlow.
Biochemical Markers of Oxidative and Nitrosative Stress in Acne Vulgaris: Correlation With Disease Activity (2013)

These findings support an association between oxidative/nitrosative stress and acne. The stronger response observed in serum samples from patients with higher GAGS scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of acne and in elucidating the mechanisms of disease pathogenesis.
Molecular characterization of hNRP, a cDNA encoding a human nucleosome-assembly-protein-I-related gene product involved in the induction of cell proliferation (1994)

We have isolated from a human thymus cDNA library a cDNA clone encoding a potential protein with 54% amino acid similarity to that encoded by a previously identified cDNA for yeast nucleosome assembly protein I (NAP-I). The deduced amino acid sequence for this newly identified cDNA, designated hNRP (human NAP-related protein), contains a potential seven-residue nuclear localization motif, three clusters of highly acidic residues and other structural features found in various proteins implicated in chromatin formation. When expressed as a fusion protein in Escherichia coli, hNRP reacted specifically with a monoclonal antibody raised against human NAP-I. The hNRP transcript was detected in all tissues and cell lines studied, but levels were somewhat increased in rapidly proliferating cells. Moreover, levels of both hNRP mRNA and protein increased rapidly in cultured T-lymphocytes induced to proliferate by incubation with phorbol ester and ionomycin. Phorbol 12-myristate 13-acetate/ionomycin-induced increases in both hNRP mRNA and mitogenesis, as measured by thymidine incorporation, were markedly inhibited, however, in cells treated with an hNRP antisense oligonucleotide. These results demonstrate a correlation between induction of hNRP expression and mitogenesis and taken together with the structural similarities between hNRP and yeast NAP-I suggest that the hNRP gene product participates in DNA replication and thereby plays an important role in the process of cell proliferation.
Self-consistent-charge density-functional tight-binding method for simulations of complex materials properties (1998)

We outline details about an extension of the tight-binding (TB) approach to improve total energies, forces, and transferability. The method is based on a second-order expansion of the Kohn-Sham total energy in density-functional theory (DFT) with respect to charge density fluctuations. The zeroth order approach is equivalent to a common standard non-self-consistent (TB) scheme, while at second order a transparent, parameter-free, and readily calculable expression for generalized Hamiltonian matrix elements may be derived. These are modified by a self-consistent redistribution of Mulliken charges (SCC). Besides the usual ``band structure'' and short-range repulsive terms the final approximate Kohn-Sham energy additionally includes a Coulomb interaction between charge fluctuations. At large distances this accounts for long-range electrostatic forces between two point charges and approximately includes self-interaction contributions of a given atom if the charges are located at one and the same atom. We apply the new SCC scheme to problems where deficiencies within the non-SCC standard TB approach become obvious. We thus considerably improve transferability.
A fast, sensitive pattern-matching approach for protein sequences (1993)

Pattern-matching algorithms are a powerful tool for finding similarities and relationships among the steadily growing amount of known protein sequences. We present a fast, sensitive pattern-matching algorithm that describes a pattern by its physico-chemical properties rather than by occurrence of amino acids, using a fast, dynamic programming algorithm. Selected examples will demonstrate applications and advantages of our approach.
Autoimmunity after Alpha-Interferon Therapy for Malignant Carcinoid Tumors (1991)

Patients with malignant carcinoid tumors may develop autoimmune disease during alpha-interferon therapy, especially when autoantibodies are present. They should therefore be monitored for autoimmunity, which does not appear, however, to influence tumor responses.